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Search Results Within Category "Blood Disorders"
52 Study Matches
A Dose Escalation and Dose Expansion Study of Intratumoral ONM-501 Alone and in Combination With Cemiplimab in Patients With Advanced Solid Tumors and Lymphomas. (ON-5001)
A phase 1, multicenter, open label, non-randomized dose escalation and dose expansion study to examine the maximum tolerated dose, (MTD), minimum effective dose (MED) and/or recommended dose for expansion (RDE) of intratumoral ONM-501 as monotherapy and in combination with a PD-1 checkpoint inhibitor in patients with advanced solid tumors and lymphomas.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Heather McArthur
195731
All
18 Years and over
Phase 1
NCT06022029
STU-2023-0921
Inclusion Criteria:
• Ability to understand and willingness to sign written informed consent before performance of any study procedures
• Age ≥ 18 years
• Participants with solid tumors or lymphomas, confirmed by available histopathology records or current biopsy, that are advanced, nonresectable, or recurrent and progressing since last antitumor therapy, and for which no alternative standard therapy exists.
• Participants must have a minimum of one injectable and measurable lesion.
• Participants with prior Hepatitis B or C are eligible if they have adequate liver function
• Participants with human immunodeficiency virus (HIV) are eligible if on established HAART for a minimum of 4 weeks prior to enrollment, have an HIV viral load <400 copies/mL, and have CD4+ T-cell (CD4+) counts ≥ 350 cells/uL
• Adequate bone marrow function:
• Adequate liver function
Exclusion Criteria:
Patients will be excluded from this study if they meet any of the
following criteria (Part 1a and Part 1b).
• Other malignancy active within the previous 2 years except for basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast that has completed curative therapy.
• Major surgery within 4 weeks before the first dose of study drug.
• Brain metastases that are untreated or in the posterior fossa or involve the meninges. Participants with stable or previously treated progressing brain metastases (except in the posterior fossa or involving the meninges) may be permitted in a case-by-case basis at the Sponsor's discretion.
• Prolongation of corrected QT (QTc) interval to >470 millisecond (ms) for males and females when electrolytes balance is normal.
• Females who are breastfeeding or pregnant at screening or baseline
• Females of childbearing potential that refuse to use a highly effective method of contraception.
• Has uncontrolled or poorly controlled hypertension as defined by a sustained BP > 9. Has received prior investigational therapy within 5 half-lives of the agent or 4 weeks before the first administration of study drug, whichever is shorter.
• Has had any major cardiovascular event within 6 months prior to study drug 10. Has known hypersensitivity to any component in the formulation of ONM-501
• Has an active infection requiring systemic treatment
• Is participating in another therapeutic clinical trial Additional Exclusion Criteria for ONM-501 in Combination with cemiplimab (Part 1b)
• Has known hypersensitivity to any component in the formulation of cemiplimab
• Has any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (>10 mg daily prednisone equivalent)
• Has a condition requiring systemic treatment with corticosteroids
Drug: ONM-501, Drug: Cemiplimab
Multiple Myeloma, Bladder Cancer, Mycosis Fungoides, Metastatic Cancer, Lymphoma, Non-Hodgkin, Skin Cancer, Head and Neck Squamous Cell Carcinoma, Triple Negative Breast Cancer, Follicular Lymphoma, Mantle Cell Lymphoma, Diffuse Large B Cell Lymphoma, Carcinoma In Situ, Brain and Nervous System, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Kidney, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Skin, Rectum, Stomach, Urinary Bladder, Hodgkins Lymphoma, Kaposis sarcoma, Lymphoid Leukemia, Non-Hodgkins Lymphoma, Small Intestine, Soft Tissue, Tumor, Solid, Uveal Melanoma, Recurrent, Cervix Cancer, Tumor Recurrence
Solid tumors, Lymphoma, ONM-501, STING, Intra-tumoral, HNSCC, Breast Cancer, Melanoma, Skin Cancer, cemiplimab, Libtayo, DLBCL, bladder cancer, cervical cancer, metastases, immunotherapy, ICI, TNBC, Triple Negative, mTNBC, anti-PD-1 antibody, BRCA1, BRCA2, anti-PD-L1, uveal, NHL, Mantle Zone lymphoma, FL, stimulator of interferon genes
UT Southwestern
Safety and Clinical Activity of KT-253 in Adult Patients With High Grade Myeloid Malignancies, Acute Lymphocytic Leukemia, Lymphoma, Solid Tumors
This Phase 1 study will evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics (PK/PD), and clinical activity of KT-253 in adult patients with relapsed or refractory (R/R) high grade myeloid malignancies, acute lymphocytic leukemia (ALL), R/R lymphoma, and R/R solid tumors. The study will identify the pharmacologically optimal dose(s) of KT-253 as the recommended Phase 2 dose (RP2D), based on all safety, PK, PD, and efficacy data.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
187698
All
18 Years and over
Phase 1
NCT05775406
STU-2023-0679
Inclusion Criteria:
• All Participants:
• Eastern Cooperative Oncology Group performance status: 0-2.
• Resolved acute effects of any prior therapy except for alopecia to baseline severity or Grade ≤1 NCI CTCAE and Grade ≤2 neuropathy
• Adequate organ function at screening
• Solid Tumors and Lymphoma (Arm A) ONLY
• Histologically or pathologically confirmed solid tumor or lymphoma.
• Relapsed and/or refractory (R/R) disease to at least two prior standard-of-care treatments or tumors for whom standard therapies are not available.
• Advanced high grade myeloid malignancies, and Acute Lymphocytic Leukemia (Arm B) ONLY
• Primary diagnosis of AML, ALL, High/Very High-risk MDS, MDS/MPN. Must be relapsed/refractory to standard therapies.
Exclusion Criteria:
• All Participants:
• Ongoing unstable cardiovascular function.
• Major surgery requiring general anesthesia within 4 weeks prior to first dose of study drug.
• History of or active concurrent malignancy unless disease-free for ≥ 2 years.
• Exposures to anticancer therapy within 2 weeks or 5 half-lives whichever is shorter; or 4 weeks from any biologics/immunotherapies or any investigational therapy prior to the first dose of study drug.
• Known presence of p53 mutation in tumor tissue
• Solid Tumors and Lymphoma (Arm A) ONLY
• Known active uncontrolled or symptomatic central nervous system (CNS) metastases.
• Autologous or allogenic hematopoietic stem cell transplant (HSCT) within six months prior to first dose of study drug or participant has progressed within six months from the day of stem cell infusion (for lymphoma participants only).
• Advanced high grade myeloid malignancies, and ALL (Arm B) ONLY
• Active CNS leukemia. Participants with symptoms suggestive of CNS disease will require a lumbar puncture to rule out CNS disease.
• Prior chemotherapy/radiation (including craniospinal radiation) within 2 weeks prior to the first dose of study drug.
• Received allogeneic hematopoietic cell transplantation (HCT) <12 weeks prior to first dose or donor lymphocyte infusion (DLI) without conditioning <4 weeks prior to first dose.
• Received autologous stem cell transplant (ASCT) < 4 weeks prior to first dose or the patient has not recovered from transplant associated toxicities to ≤ grade 1 prior to the first dose of study drug.
• Received chimeric antigen receptor therapy or other modified T cell therapy <3 weeks prior to the first dose.
• Patients with signs or symptoms of Grade ≥ 2 acute or chronic graft versus host disease (GVHD) within 2 weeks of enrollment.
Drug: KT-253
Multiple Myeloma, Advanced Solid Tumors, Acute Lymphocytic Leukemia, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Esophagus, Kidney, Larynx, Liver, Lung/Thoracic, Ovary, Pancreas, Prostate, Rectum, Stomach, Thyroid, Leukemia, Other, Leukemia, Not Otherwise Specified, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Myeloid Malignancies, Lymphomas
KT-253, MDM2, High Grade MDS/MPN, ALL, AML, Lymphoma, Solid tumor
UT Southwestern
A Study to Investigate the Safety and Tolerability of Ziftomenib in Combination With Venetoclax/Azacitidine, Venetoclax, or 7+3 in Patients With AML
This Phase 1 study will assess the safety, tolerability, and preliminary antileukemic activity of ziftomenib in combination with venetoclax and azacitidine (ven/aza), ven, and 7+3 for two different molecularly-defined arms, NPM1-m and KMT2A-r.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
187698
All
18 Years and over
Phase 1
NCT05735184
STU-2023-0858
Key
• Patients must have a documented NPM1 mutation or KMT2A rearrangement and have either newly diagnosed or relapsed/refractory AML
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Adequate liver, renal, and cardiac function according to protocol defined criteria
• A female of childbearing potential must agree to use adequate contraception from the time of screening through 180 days following the last dose of study intervention. A male of childbearing potential must agree to use abstinence or adequate contraception from the time of screening through 90 days following the last dose of study intervention Key
• Diagnosis of either acute promyelocytic leukemia or blast chronic myelomonocytic leukemia
• Known history of BCR-ABL alteration
• Advanced malignant hepatic tumor [for patients receiving ven/aza combination]
• Administration of live attenuated vaccines within 14 days prior to, during, or after treatment until B-cell recovery
• Active central nervous system (CNS) involvement by AML.
• Clinical signs/symptoms of leukostasis or WBC > 25,000 / microliter. Hydroxyurea and/or leukapheresis are permitted to meet this criterion
• Not recovered to Grade ≤1 (NCI-CTCAE v5.0) from all nonhematological toxicities except for alopecia
• Known clinically active human immunodeficiency virus, active hepatitis B or active hepatitis C infection
• For newly diagnosed cohorts: received prior chemotherapy for leukemia, except hydroxyurea and/or leukapheresis to control leukocytosis, prior treatment with all-transretinoic acid for initially suspected acute promyelocytic leukemia, or non-HMA therapy for prior myelodysplastic syndrome
• For relapsed/refractory cohorts: received chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy that is considered to be investigational < 14 days prior to the first dose of ziftomenib or within 5 drug half-lives prior to the first dose of study drug
• Uncontrolled intercurrent illness including, but not limited to, cardiac illness as defined in the protocol
• Mean corrected QT interval corrected for heart rate by Fredericia's formula (QTcF) >480 ms on triplicate ECGs
• Uncontrolled infection
• Women who are pregnant or lactating
• An active malignancy and currently receiving chemotherapy for that malignancy or disease that is uncontrolled/progressing
Inclusion Criteria:
• Patients must have a documented NPM1 mutation or KMT2A rearrangement and have either newly diagnosed or relapsed/refractory AML
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Adequate liver, renal, and cardiac function according to protocol defined criteria
• A female of childbearing potential must agree to use adequate contraception from the time of screening through 180 days following the last dose of study intervention. A male of childbearing potential must agree to use abstinence or adequate contraception from the time of screening through 90 days following the last dose of study intervention Key
Exclusion Criteria:
• Diagnosis of either acute promyelocytic leukemia or blast chronic myelomonocytic leukemia
• Known history of BCR-ABL alteration
• Advanced malignant hepatic tumor [for patients receiving ven/aza combination]
• Administration of live attenuated vaccines within 14 days prior to, during, or after treatment until B-cell recovery
• Active central nervous system (CNS) involvement by AML.
• Clinical signs/symptoms of leukostasis or WBC > 25,000 / microliter. Hydroxyurea and/or leukapheresis are permitted to meet this criterion
• Not recovered to Grade ≤1 (NCI-CTCAE v5.0) from all nonhematological toxicities except for alopecia
• Known clinically active human immunodeficiency virus, active hepatitis B or active hepatitis C infection
• For newly diagnosed cohorts: received prior chemotherapy for leukemia, except hydroxyurea and/or leukapheresis to control leukocytosis, prior treatment with all-transretinoic acid for initially suspected acute promyelocytic leukemia, or non-HMA therapy for prior myelodysplastic syndrome
• For relapsed/refractory cohorts: received chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy that is considered to be investigational < 14 days prior to the first dose of ziftomenib or within 5 drug half-lives prior to the first dose of study drug
• Uncontrolled intercurrent illness including, but not limited to, cardiac illness as defined in the protocol
• Mean corrected QT interval corrected for heart rate by Fredericia's formula (QTcF) >480 ms on triplicate ECGs
• Uncontrolled infection
• Women who are pregnant or lactating
• An active malignancy and currently receiving chemotherapy for that malignancy or disease that is uncontrolled/progressing
Drug: Ziftomenib, Drug: Venetoclax, Drug: Azacitidine, Drug: Daunorubicin, Drug: Cytarabine
Acute Myeloid Leukemia, Myeloid Sarcoma, Mixed Phenotype Acute Leukemia, Mixed Lineage Acute Leukemia, Acute Myeloid Leukemia, in Relapse, Mixed Lineage Leukemia Gene Mutation, Refractory AML, AML With Mutated NPM1, Acute Myeloid Leukemia Recurrent, NPM1 Mutation, KMT2Ar
UT Southwestern
DEFIANCE: RCT of ClotTriever System Versus Anticoagulation In Deep Vein Thrombosis (DEFIANCE)
This study is a prospective, multicenter, randomized controlled trial of an interventional strategy using the ClotTriever System to achieve and maintain vessel patency (ClotTriever Intervention Arm) versus conservative medical management using anticoagulation therapy alone (Conservative Medical Management Arm) in the treatment of subjects with symptomatic unilateral iliofemoral DVT. The study will collect data on demographics, comorbidities, details from the DVT diagnosis and treatment, and clinical outcomes through the 6-month follow up visit.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Ana.Garzon@UTSouthwestern.edu
Michael Siah
186697
All
18 Years and over
N/A
NCT05701917
STU-2023-0117
Inclusion Criteria
• Age ≥ 18 years
• Proximal lower extremity unilateral DVT involving at least the common femoral, external iliac, or common iliac veins, alone or in combination
• Symptom onset within 12 weeks of enrollment in the study
• Significant symptoms, as defined by a Villalta score > 9
• Willing and able to provide informed consent Exclusion Criteria
• Bilateral iliofemoral DVT
• Prior venous stent in the target venous segment
• IVC aplasia/hypoplasia or other congenital anatomic anomalies of the IVC or iliac veins
• IVC filter in place at the time of enrollment
• Limb-threatening circulatory compromise (e.g., phlegmasia)
• Clot in transit including IVC thrombus presenting as extension of >2cm into the IVC from the CIV
• Symptomatic PE with right heart strain where the physician judges that a DVT intervention is inappropriate at this time.
• Inability to be a candidate for intervention due to medical or technical reasons based on physician judgement
• Severe allergy, hypersensitivity to, or thrombocytopenia from heparin
• Severe allergy to iodinated contrast agents that cannot be mitigated
• Hemoglobin < 8.0 g/dL, INR > 1.7 before warfarin was started, or platelets < 50,000/µl which cannot be corrected prior to enrollment
• Severe renal impairment (estimated GFR < 30 ml/min) in patients who are not yet on dialysis
• Inability to provide therapeutic anticoagulation per Investigator discretion
• Uncontrolled severe hypertension on repeated readings (systolic > 180mmHg or diastolic > 105mmHg)
• Recently (< 30 days) had DVT interventional procedure
• Subject is participating in another study that may interfere with this study
• Life expectancy < 6 months or chronic non-ambulatory status
• Known hypercoagulable states that, in the opinion of the Investigator, cannot be medically managed throughout the study period
• Subject has any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the subject (e.g., contraindication to use of ClotTriever per local approved labeling, compromise the well-being or that could prevent, limit, or confound the protocol-specified assessments)
• Subject has previously completed or withdrawn from this study
• Patient unwilling or unable to conduct the follow up visits per protocol
• Age ≥ 18 years
• Proximal lower extremity unilateral DVT involving at least the common femoral, external iliac, or common iliac veins, alone or in combination
• Symptom onset within 12 weeks of enrollment in the study
• Significant symptoms, as defined by a Villalta score > 9
• Willing and able to provide informed consent Exclusion Criteria
• Bilateral iliofemoral DVT
• Prior venous stent in the target venous segment
• IVC aplasia/hypoplasia or other congenital anatomic anomalies of the IVC or iliac veins
• IVC filter in place at the time of enrollment
• Limb-threatening circulatory compromise (e.g., phlegmasia)
• Clot in transit including IVC thrombus presenting as extension of >2cm into the IVC from the CIV
• Symptomatic PE with right heart strain where the physician judges that a DVT intervention is inappropriate at this time.
• Inability to be a candidate for intervention due to medical or technical reasons based on physician judgement
• Severe allergy, hypersensitivity to, or thrombocytopenia from heparin
• Severe allergy to iodinated contrast agents that cannot be mitigated
• Hemoglobin < 8.0 g/dL, INR > 1.7 before warfarin was started, or platelets < 50,000/µl which cannot be corrected prior to enrollment
• Severe renal impairment (estimated GFR < 30 ml/min) in patients who are not yet on dialysis
• Inability to provide therapeutic anticoagulation per Investigator discretion
• Uncontrolled severe hypertension on repeated readings (systolic > 180mmHg or diastolic > 105mmHg)
• Recently (< 30 days) had DVT interventional procedure
• Subject is participating in another study that may interfere with this study
• Life expectancy < 6 months or chronic non-ambulatory status
• Known hypercoagulable states that, in the opinion of the Investigator, cannot be medically managed throughout the study period
• Subject has any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the subject (e.g., contraindication to use of ClotTriever per local approved labeling, compromise the well-being or that could prevent, limit, or confound the protocol-specified assessments)
• Subject has previously completed or withdrawn from this study
• Patient unwilling or unable to conduct the follow up visits per protocol
Device: ClotTriever System, Drug: Commercially available/market approved anticoagulation medication including but not limited to: Heparin Sodium, Coumadin, Rivaroxaban, Apixaban, etc.
Venous Thromboembolism, Deep Venous Thrombosis, Post-Thrombotic Syndrome
Venous Thromboembolism, Deep Venous Thrombosis, Post-Thrombotic Syndrome, Anticoagulation, Percutaneous Mechanical Thrombectomy
UT Southwestern
A Study to Test a Medicine (Fitusiran) Injected Under the Skin for Preventing Bleeding Episodes in Male Adolescent or Adult Participants With Severe Hemophilia (ATLAS-NEO)
This is a multicenter, multinational, open-label, one-way cross-over, Phase 3, single-arm study for treatment of hemophilia. The purpose of this study is to measure the frequency of treated bleeding episodes with fitusiran in male adult and adolescent (≥12 years old) participants with hemophilia A or B, with or without inhibitory antibodies to factor VIII or IX who have switched from their prior standard of care treatment. The total study duration will be up to approximately 50 months (200 weeks, 1 study month is equivalent to 4 weeks) and will include: - A screening period up to approximately 60 days, - A standard of care (SOC) period of approximately 6 study months (24 weeks), - A fitusiran treatment period of approximately 36 study months (144 weeks), - An antithrombin (AT) follow-up period of approximately 6 study months (24 weeks) but may be shorter or longer depending on individual participants AT recovery. The frequency for telephone visits will be approximately every 2 weeks. For site visits the frequency will be approximately every 8 weeks during the SOC period and approximately every 4 weeks during the fitusiran treatment period. If applicable and if allowed by local regulation, home and/or remote visits may be conducted during the study
Call 214-648-5005
studyfinder@utsouthwestern.edu, susan.corley@childrens.com
Jessica Garcia
181672
Male
12 Years and over
Phase 3
NCT05662319
STU-2023-0024
Inclusion Criteria:
• Diagnosis of severe congenital hemophilia A or B (FVIII <1% or FIX level ≤2%) as evidenced by a central laboratory measurement at screening or documented medical record evidence.
• For participants currently not on prophylaxis (CFC or BPA on-demand): A minimum of 4 bleeding episodes requiring BPA (inhibitor participants) or CFC (non-inhibitor participants) treatment within the last 6 months prior to screening.
• Willing and able to comply with the study requirements and to provide written informed consent and assent in the case of participants under the age of legal consent, per local and national requirements
Exclusion Criteria:
• Known co-existing bleeding disorders other than congenital hemophilia A or B
• History of arterial or venous thromboembolism, not associated with an indwelling venous access
• History of intolerance to SC injection(s).
• Current participation in immune tolerance induction therapy (ITI)
• Prior gene therapy
• Current or prior participation in a fitusiran trial
• Current or prior participation in a gene therapy trial
• Received an investigational drug or device within 30 days prior to the screening visit or within 5 half-lives of the investigational drug (or device) prior to the screening visit, whichever is longer
• Presence of clinically significant liver disease AT activity <60% at Screening
• Co-existing thrombophilic disorder
• Hepatitis C virus antibody positive, except participants who have negative Hepatitis C viral load and no evidence of cirrhosis
• Presence of acute hepatitis, ie, hepatitis A, hepatitis E.
• Presence of acute or chronic hepatitis B infection
• Known to be HIV positive with CD4 count <200 cells/μL.
• Reduced renal function The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Drug: Fitusiran, Drug: Clotting factor concentrates (CFC) or bypassing agents (BPA), Drug: Antithrombin concentrate (ATIIIC)
Hemophilia
Children’s Health
A Study of an MMSET Inhibitor in Patients With Relapsed and Refractory Multiple Myeloma
A Phase I study to evaluate the safety of a novel, orally available, selective, and potent small molecule inhibitor of the histone lysine methyl transferase MMSET (also known as NSD2/WHSC1) to prevent the dimethylation of H3K36 in adult patients with relapsed or refractory multiple myeloma (RRMM).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Aimaz Afrough
208007
All
18 Years and over
Phase 1
NCT05651932
STU-2023-0538
Key
• ≥ 18 years of age
• ECOG score ≤ 2
• Relapsed or refractory multiple myeloma (as per IMWG)
• ≥ 3 prior lines of therapy, including a PI, an IMiD, and an anti-CD38 antibody
• Patients must have exhausted available therapeutic options that are expected to provide a meaningful clinical benefit, either through disease relapse, treatment refractory disease, intolerance, or refusal of the therapy
• t(4;14) confirmed by standard of care FISH testing, or GOF mutation in MMSET confirmed by local sequencing test (Part B dose expansion cohorts only)
• Measurable disease, including at least 1 of the following criteria:
• Serum M protein ≥ 0.50 g/dL (by SPEP)
• Serum IgA ≥ 0.50 g/dL (IgA myeloma patients)
• Urine M protein ≥ 200 mg/24 h (by UPEP)
• sFLC involved light chain ≥ 10 mg/dL (100 mg/L) (patients with abnormal sFLC ratio)
• ≥ 1 extramedullary lesion ≥ 1 cm in size and able to be followed by imaging assessments (Part A dose escalation cohorts only)
• Bone marrow plasma cells ≥ 10% (Part A dose escalation cohorts only) Key
• Treatment with the following therapies in the specified time period prior to first dose:
• Radiation, chemotherapy, immunotherapy, or any other anticancer therapy ≤ 2 weeks
• Cellular therapies ≤ 8 weeks
• Autologous transplant < 100 days
• Allogenic transplant ≤ 6 months, or > 6 months with active GVHD
• Major surgery ≤ 4 weeks
• History of or current plasma cell leukemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, and skin changes) syndrome, solitary bone lesion or bone lesions as the only evidence for plasma cell dyscrasia, myelodysplastic syndrome or a myeloproliferative neoplasm or light chain amyloidosis
• Active CNS disease
• Inadequate bone marrow function
• Inadequate renal, hepatic, pulmonary, and cardiac function
• Active, ongoing, or uncontrolled systemic viral, bacterial, or fungal infection. Permitted prophylactic medications, antimicrobials or antiretroviral therapies defined in protocol.
• Use of acid reducing agents and strong inhibitors or inducers of CYP3A4 within 14 days or 5 half-lives prior to first dose
• Active malignancy not related to myeloma requiring therapy within < 3 years prior to enrollment, or not in complete remission, with exceptions defined in protocol.
Inclusion Criteria:
• ≥ 18 years of age
• ECOG score ≤ 2
• Relapsed or refractory multiple myeloma (as per IMWG)
• ≥ 3 prior lines of therapy, including a PI, an IMiD, and an anti-CD38 antibody
• Patients must have exhausted available therapeutic options that are expected to provide a meaningful clinical benefit, either through disease relapse, treatment refractory disease, intolerance, or refusal of the therapy
• t(4;14) confirmed by standard of care FISH testing, or GOF mutation in MMSET confirmed by local sequencing test (Part B dose expansion cohorts only)
• Measurable disease, including at least 1 of the following criteria:
• Serum M protein ≥ 0.50 g/dL (by SPEP)
• Serum IgA ≥ 0.50 g/dL (IgA myeloma patients)
• Urine M protein ≥ 200 mg/24 h (by UPEP)
• sFLC involved light chain ≥ 10 mg/dL (100 mg/L) (patients with abnormal sFLC ratio)
• ≥ 1 extramedullary lesion ≥ 1 cm in size and able to be followed by imaging assessments (Part A dose escalation cohorts only)
• Bone marrow plasma cells ≥ 10% (Part A dose escalation cohorts only) Key
Exclusion Criteria:
• Treatment with the following therapies in the specified time period prior to first dose:
• Radiation, chemotherapy, immunotherapy, or any other anticancer therapy ≤ 2 weeks
• Cellular therapies ≤ 8 weeks
• Autologous transplant < 100 days
• Allogenic transplant ≤ 6 months, or > 6 months with active GVHD
• Major surgery ≤ 4 weeks
• History of or current plasma cell leukemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, and skin changes) syndrome, solitary bone lesion or bone lesions as the only evidence for plasma cell dyscrasia, myelodysplastic syndrome or a myeloproliferative neoplasm or light chain amyloidosis
• Active CNS disease
• Inadequate bone marrow function
• Inadequate renal, hepatic, pulmonary, and cardiac function
• Active, ongoing, or uncontrolled systemic viral, bacterial, or fungal infection. Permitted prophylactic medications, antimicrobials or antiretroviral therapies defined in protocol.
• Use of acid reducing agents and strong inhibitors or inducers of CYP3A4 within 14 days or 5 half-lives prior to first dose
• Active malignancy not related to myeloma requiring therapy within < 3 years prior to enrollment, or not in complete remission, with exceptions defined in protocol.
Drug: KTX-1001
Multiple Myeloma, Myeloid and Monocytic Leukemia, Myeloma, Myeloma Multiple
NSD2, MMSET, WHSC1, T4,14, T(4,14), translocation, myeloma, RRMM
UT Southwestern
Study to Compare Axicabtagene Ciloleucel With Standard of Care Therapy as First-line Treatment in Participants With High-risk Large B-cell Lymphoma (ZUMA-23)
The goal of this clinical study is to compare the study drug, axicabtagene ciloleucel, versus standard of care (SOC) in first-line therapy in participants with high-risk large B-cell lymphoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Praveen Ramakrishnan Geethakumari
171719
All
18 Years and over
Phase 3
NCT05605899
STU-2023-0133
Key
• Histologically confirmed large B cell lymphoma (LBCL) based on 2016 World Health Organization (WHO) classification by local pathology lab assessment, including of the following:
• Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS)
• High-grade B-cell lymphoma (HGBL)
• Note: Transformed DLBCL from follicular lymphoma or from marginal zone lymphoma is eligible if no prior treatment with anthracycline-containing regimen.
• High-risk disease defined as an International Prognostic Index (IPI) score of 4 or 5 at initial diagnosis.
• Have received only 1 cycle of rituximab plus chemotherapy (R-chemotherapy).
• Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function.
• Females of childbearing potential must have a negative serum or urine pregnancy test. Key
• The following WHO 2016 subcategories by local assessment:
• T-cell/histiocyte-rich LBCL
• Primary DLBCL of the central nervous system (CNS)
• Primary mediastinal (thymic) LBCL
• B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma
• Burkitt lymphoma
• History of Richter's transformation of chronic lymphocytic leukemia
• Presence of detectable cerebrospinal fluid (CSF)-malignant cells, brain metastases, or a history of CNS involvement of lymphoma.
• Presence of cardiac lymphoma involvement.
• Any prior treatment for LBCL other than the 1 cycle of R-chemotherapy.
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• Presence of CNS disorder. History of stroke, transient ischemic attack, or posterior reversible encephalopathy syndrome (PRES) within 12 months prior to enrollment.
• History of acute or chronic active hepatitis B or C infection.
• Positive for human immunodeficiency virus (HIV) unless taking appropriate anti-HIV medications, with an undetectable viral load by PCR and with a cluster of differentiation 4 (CD4) count > 200 cells/uL.
• Medical conditions or residual toxicities from prior therapies likely to interfere with assessment of safety or efficacy of study treatment. Please refer to protocol for further details.
• History of clinically significant cardiac disease within 12 months before enrollment.
• History of any medical condition requiring maintenance systemic immunosuppression/systemic disease modifying agents within the last 2 years. Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Inclusion Criteria:
• Histologically confirmed large B cell lymphoma (LBCL) based on 2016 World Health Organization (WHO) classification by local pathology lab assessment, including of the following:
• Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS)
• High-grade B-cell lymphoma (HGBL)
• Note: Transformed DLBCL from follicular lymphoma or from marginal zone lymphoma is eligible if no prior treatment with anthracycline-containing regimen.
• High-risk disease defined as an International Prognostic Index (IPI) score of 4 or 5 at initial diagnosis.
• Have received only 1 cycle of rituximab plus chemotherapy (R-chemotherapy).
• Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function.
• Females of childbearing potential must have a negative serum or urine pregnancy test. Key
Exclusion Criteria:
• The following WHO 2016 subcategories by local assessment:
• T-cell/histiocyte-rich LBCL
• Primary DLBCL of the central nervous system (CNS)
• Primary mediastinal (thymic) LBCL
• B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma
• Burkitt lymphoma
• History of Richter's transformation of chronic lymphocytic leukemia
• Presence of detectable cerebrospinal fluid (CSF)-malignant cells, brain metastases, or a history of CNS involvement of lymphoma.
• Presence of cardiac lymphoma involvement.
• Any prior treatment for LBCL other than the 1 cycle of R-chemotherapy.
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• Presence of CNS disorder. History of stroke, transient ischemic attack, or posterior reversible encephalopathy syndrome (PRES) within 12 months prior to enrollment.
• History of acute or chronic active hepatitis B or C infection.
• Positive for human immunodeficiency virus (HIV) unless taking appropriate anti-HIV medications, with an undetectable viral load by PCR and with a cluster of differentiation 4 (CD4) count > 200 cells/uL.
• Medical conditions or residual toxicities from prior therapies likely to interfere with assessment of safety or efficacy of study treatment. Please refer to protocol for further details.
• History of clinically significant cardiac disease within 12 months before enrollment.
• History of any medical condition requiring maintenance systemic immunosuppression/systemic disease modifying agents within the last 2 years. Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Biological: Axicabtagene Ciloleucel, Drug: Cyclophosphamide, Drug: Fludarabine, Drug: Etoposide, Drug: Rituximab, Drug: Doxorubicin, Drug: Vincristine, Drug: Prednisone
Non-Hodgkins Lymphoma, Other Hematopoietic, Soft Tissue, High-risk Large B-cell Lymphoma (LBCL)
UT Southwestern
A Trial Comparing Unrelated Donor BMT With IST for Pediatric and Young Adult Patients With Severe Aplastic Anemia (TransIT, BMT CTN 2202) (TransIT)
Severe Aplastic Anemia (SAA) is a rare condition in which the body stops producing enough new blood cells. SAA can be cured with immune suppressive therapy or a bone marrow transplant. Regular treatment for patients with aplastic anemia who have a matched sibling (brother or sister), or family donor is a bone marrow transplant. Patients without a matched family donor normally are treated with immune suppressive therapy (IST). Match unrelated donor (URD) bone marrow transplant (BMT) is used as a secondary treatment in patients who did not get better with IST, had their disease come back, or a new worse disease replaced it (like leukemia). This trial will compare time from randomization to failure of treatment or death from any cause of IST versus URD BMT when used as initial therapy to treat SAA. The trial will also assess whether health-related quality of life and early markers of fertility differ between those randomized to URD BMT or IST, as well as assess the presence of marrow failure-related genes and presence of gene mutations associated with MDS or leukemia and the change in gene signatures after treatment in both study arms. This study treatment does not include any investigational drugs. The medicines and procedures in this study are standard for treatment of SAA.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Laurie.Rodgers-Augustyniak@childrens.com
Tiffany Simms-Waldrip
119738
All
0 Years to 25 Years old
Phase 3
NCT05600426
STU-2022-0964
Inclusion Criteria:
To be eligible to participate in the randomized trial, an individual must meet all the
following criteria:
• Provision of signed and dated informed consent form for the randomized trial by patient and/or legal guardian.
• Age ≤25 years old at time of randomized trial consent.
• Confirmed diagnosis of idiopathic SAA, defined as:
• Bone marrow cellularity <25%, or <30% hematopoietic cells.
• Two of three of the following (in peripheral blood): neutrophils <0.5 x 10^9/L, platelets <20 x 10^9/L, absolute reticulocyte count <60 x 10^9/L or hemoglobin <8 g/dL.
• No suitable fully matched related donor available (minimum 6/6 match for HLA-A and B at intermediate or high resolution and DRB1 at high resolution using DNA based typing).
• At least 2 unrelated donors noted on NMDP search who are well matched (9/10 or 10/10 for HLA-A, B, C, DRB1, and DQB1 using high resolution).
• In the treating physician's opinion, no obvious contraindications precluding them from BMT or IST.
Exclusion Criteria:
• Presence of Inherited bone marrow failure syndromes (IBMFS). The diagnosis of Fanconi anemia must be excluded by diepoxybutane (DEB) or equivalent testing on peripheral blood or marrow. Telomere length testing should be sent on all patients to exclude Dyskeratosis Congenita (DC), but if results are delayed or unavailable and there are no clinical manifestations of DC, patients may enroll. If patients have clinical characteristics suspicious for Shwachman-Diamond syndrome, this disorder should be excluded by pancreatic isoamylase testing or gene mutation analysis (note: pancreatic isoamylase testing is not useful in children <3). Other testing per center may be performed to exclude IBMFS.
• Clonal cytogenetic abnormalities or Fluorescence In-Situ Hybridization (FISH) pattern consistent with pre- myelodysplastic syndrome (pre-MDS) or MDS on marrow examination.
• Known severe allergy to ATG.
• Prior allogeneic or autologous stem cell transplant.
• Prior solid organ transplant.
• Infection with human immunodeficiency virus (HIV).
• Active Hepatitis B or C. This only needs to be excluded in patients where there is clinical suspicion of hepatitis (e.g., elevated LFTs).
• Female patients who are pregnant or breast-feeding.
• Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ.
• Disease modifying treatment prior to study enrollment, including but not limited to use of androgens, eltrombopag, romiplostim, or immune suppression. Note: Supportive care measures such as G-CSF, blood transfusion support and antibiotics are allowable
Drug: cyclosporine, Procedure: Matched Unrelated Donor Hematopoetic Stem Cell Transplant, Drug: horse anti-thymocyte globulin (ATG), Drug: rabbit anti-thymocyte globulin (ATG), Drug: Methotrexate, Drug: Fludarabine, Drug: Cyclophosphamide, Radiation: low-dose total body irradiation (TBI), Procedure: Immunosuppressive Therapy (IST)
Severe Aplastic Anemia
Children’s Health
Study of SGR-1505 in Mature B-Cell Neoplasms
The purpose of this study is to evaluate safety and tolerability and to determine the maximum tolerated dose (MTD) and/or recommended dose (RD) of SGR-1505.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Heather Wolfe
162875
All
18 Years and over
Phase 1
NCT05544019
STU-2023-0636
Inclusion Criteria:
• Subject must have a history of histologically or cytologically confirmed mature B-cell malignancy.
• Subject must have measurable or detectable disease according to the applicable disease-specific classification system.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Life expectancy ≥ 12 weeks.
Exclusion Criteria:
• For a subject with indolent NHL and CLL/SLL, the subject is in need of immediate cytoreductive therapy (unless the patient has no remaining treatment choice with potential benefit) and has an indication for treatment.
• Subject has previous invasive malignancy in the last 2 years.
• Subject has a known allergy to SGR-1505 or excipients of SGR-1505.
• Subject has symptomatic or active CNS involvement of disease.
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that would place the participant at increased risk to the use of an investigational drug.
Drug: SGR-1505
Splenic Marginal Zone Lymphoma, Waldenström Macroglobulinemia, Chronic Lymphocytic Leukemia, Burkitt Lymphoma, Plasmablastic Lymphoma, Follicular Lymphoma, Nodal Marginal Zone Lymphoma, ALK-Positive Large B-Cell Lymphoma, Primary Cutaneous Diffuse Large B-Cell Lymphoma, Primary Effusion Lymphoma, Non Hodgkin Lymphoma, Mantle Cell Lymphoma, Lymphoid Leukemia, Non-Hodgkins Lymphoma, High-grade B-cell Lymphoma, Primary Mediastinal Large B Cell Lymphoma, Lymphoplasmacytic Lymphoma, DLBCL, EBV-Positive DLBCL, Nos, Mature B-Cell Neoplasm, MALT Lymphoma, Pediatric-Type Follicular Lymphoma, IRF4 Gene Rearrangement, Primary Cutaneous Follicle Center Lymphoma, DLBCL Germinal Center B-Cell Type, T-Cell/Histiocyte Rich Lymphoma, HHV8-Positive DLBCL, Nos, Duodenal-Type Follicular Lymphoma
MALT1, NF-kB
UT Southwestern
Study of Anitocabtagene-autoleucel in Relapsed or Refractory Multiple Myeloma (iMMagine-1) (iMMagine-1)
A Phase II study of anitocabtagene-autoleucel (formerly CART-ddBCMA) for patients with relapsed or refractory multiple myeloma. Anitocabtagene-autoleucel is a BCMA-directed CAR-T cell therapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Gurbakhash Kaur
197903
All
18 Years and over
Phase 2
NCT05396885
STU-2022-0687
Inclusion Criteria:
• Age 18 years or older and has capacity to give informed consent
• Relapsed or refractory multiple myeloma treated with at least 3 prior regimens of systemic therapy including proteasome inhibitor, immunomodulatory drugs (IMiD) and anti-CD38 antibody and are refractory to the last line of therapy. For each line, 2 consecutive cycles are required unless the best response after 1 cycle was progressive disease. Note: IMWG criteria defines refractory disease as disease progression on or within 60 days of a therapy Note: Induction treatment with or without hematopoietic stem cell transplant and with or without maintenance is considered a single regimen
• Documented measurable disease including at least one or more of the following criteria:
• Serum M-protein ≥1.0 g/dL
• Urine M-protein ≥200 mg/24 hours
• Involved serum free light chain ≥10 mg/dL with abnormal κ/λ ratio (i.e., >4:1 or <1:2)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Life expectancy >12 weeks
• Adequate organ function defined as:
• Oxygen (O2) saturation ≥92% on room air
• Left Ventricular Ejection Fraction (LVEF) ≥45% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan
• Absolute neutrophil count (ANC) ≥1.0k/µl, platelet count (PLT) ≥50k/µl, [NOTE: Platelet transfusion not allowed within 14 days; filgrastim (or biosimilar) not allowed within 7 days, pegfilgrastim (or biosimilar) within 14 days]
• Creatinine clearance ≥45 mL/min min (as determined by the Cockgroft-Gault equation) and not on dialysis
• Aspartate transaminase (AST)/alanine transaminase (ALT) <3 x upper limits of normal (ULN)
• Total bilirubin <1.5 x ULN (allow 3x ULN for Gilbert's syndrome)
• Prothrombin time test (PTT), prothrombin time (PT)/international normalized ratio (INR) <1.5 x ULN, unless on a stable dose of anti-coagulant for a thromboembolic event (Subjects with any history of thromboembolic stroke; or history or Grade 2 (G2) or greater hemorrhage within one year are excluded)
• Resolution of adverse events (AEs) from any prior systemic anticancer therapy, radiotherapy, or surgery to Grade 1 or baseline (except G2 alopecia and G2 sensory neuropathy)
• Male and female participants of childbearing potential must agree to use highly effective methods of birth control through 12 months after the dose of study treatment
• Willing to comply with and able to tolerate study procedures, including consent to participate in separate Long-term Safety Follow-up lasting up to 15 years per FDA guidance
• Subject's leukapheresis product from non-mobilized cells is received and accepted for cell processing by manufacturing site. NOTE: Leukapheresis will be performed only after all other eligibility criteria are confirmed
Exclusion Criteria:
• Plasma cell leukemia or history of plasma cell leukemia
• Treatment with the following therapies as specified below
• Any prior systemic treatment for multiple myeloma within the 14 days prior to scheduled leukapheresis
• Receiving high-dose (e.g., >10 mg prednisone or equivalent) systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to leukapheresis
• Prior treatment with any gene therapy or gene-modified cellular immune-therapy
• Prior B-cell maturation antigen (BCMA) directed therapy
• Autologous stem cell transplantation within 3 months prior to leukapheresis, or any prior allogeneic stem cell transplantation
• Subjects with solitary plasmacytomas without evidence of other measurable disease are excluded
• History of allergy or hypersensitivity to study drug components. Subjects with a history of severe hypersensitivity reaction to dimethyl sulphoxide (DMSO) are excluded
• Contraindication to fludarabine or cyclophosphamide
• Severe or uncontrolled intercurrent illness or laboratory abnormalities including
• Active bacterial, viral, or fungal infection requiring systemic treatment (isolated fever may not constitute active infection in and of itself, (e.g., related to disease)
• Symptomatic congestive heart failure (i.e., New York Heart Association stage III or IV)
• Unstable angina, arrhythmia, or myocardial infarction (MI) within 6 months prior to Screening
• Significant pulmonary dysfunction
• Uncontrolled thromboembolic events or recent severe hemorrhage (i.e., within one year)
• Any history of pulmonary embolism (PE) in the past 12 months or deep vein thrombosis (DVT) within three months of enrollment. Therapeutic dosing of anticoagulants (e.g., warfarin, low molecular weight heparin, Factor Xa inhibitors) is allowed for history of PE/DVT if greater than twelve and three months, respectively, from time of enrollment, and should be at a stable maintenance dose.
• Auto-immune disease requiring immunosuppressive therapy within the last 24 months
• Seropositive for and with evidence of active hepatitis B or C infection at time of Screening, or HIV seropositive
• Subjects with a history of hepatitis B but have received antiviral therapy and have non-detectable viral DNA are eligible
• Subjects seropositive because of hepatitis B virus vaccine with no signs or active infection are eligible
• Subjects who had hepatitis C but have received antiviral therapy and show no detectable hepatitis C virus (HCV) viral RNA are eligible
• Active central nervous system (CNS) involvement by malignancy
• Any sign of active or prior CNS pathology including but not limited to history of epilepsy, seizure, paresis, aphasia, stroke, subarachnoid hemorrhage or CNS bleed, severe brain injury, dementia, cerebellar disease, Parkinson's disease, organic brain syndrome or psychosis
• Active malignancy not related to myeloma that has required therapy in the last 3 years or is not in complete remission. Exceptions to this criterion include successfully treated non-metastatic basal cell or squamous cell skin carcinoma, or prostate cancer that does not require therapy.
• Females who are pregnant or breastfeeding or females of childbearing potential not using an effective method of birth control
• Subjects with any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in study (or full access to medical records) as written including follow up, the interpretation of data or place the subject at unacceptable risk
• Any vaccine ≤ 6 weeks before leukapheresis and/or anticipation of the need for such a vaccine during the subject's participation in the study
• Concurrent enrollment on another study using an investigational therapy for the treatment of RRMM
Biological: anitocabtagene-autoleucel
Multiple Myeloma
UT Southwestern
A Study to Assess Adverse Events and Change in Disease Activity of Intravenously (IV) Infused ABBV-383 in Combination With Anti-Cancer Regimens for the Treatment of Adult Participants With Relapsed/Refractory Multiple Myeloma
Multiple myeloma (MM) is a plasma cell disease characterized by the growth of clonal plasma cells in the bone marrow. The purpose of this study is to assess the safety and toxicity of ABBV-383 when co-administered with pomalidomide-dexamethasone (Pd), lenalidomide-dexamethasone (Rd), daratumumab-dexamethasone (Dd), or nirogacestat (Niro) in adult participants with relapsed/refractory (R/R) multiple myeloma (MM). Adverse events and change in disease activity will be assessed. ABBV-383 is an investigational drug being developed for the treatment of R/R MM. Study doctors put the participants in groups called treatment arms. ABBV-383 co-administered with Pd, Rd, Dd, or Niro will be explored. Each treatment arm receives a different treatment combination depending on stage of the study and eligibility. This study will include a dose escalation phase to determine the best dose of ABBV-383, followed by a dose expansion phase to confirm the dose. Approximately 270 adult participants with R/R MM will be enrolled in the study in approximately 45 sites worldwide. Participants will receive intravenous (IV) ABBV-383 co-administered with oral/IV Pd, oral/IV Rd, oral/IV/subcutaneous (SC) Dd, or oral/IV Niro in 28-day cycles. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Larry Anderson
102991
All
18 Years and over
Phase 1
NCT05259839
STU-2022-0348
Inclusion Criteria:
• Eastern Cooperative Oncology Group (ECOG) performance of <= 2.
• Must have confirmed diagnosis of Relapsed/Refractory (R/R) Multiple Myeloma (MM) with documented evidence of progression during or after the participant's last treatment regimen based on the investigator's determination of the International Myeloma Working Group (IMWG) criteria.
• Must have measurable disease as outlined in the protocol.
• Must be naïve to treatment with ABBV-383 and must have never received BCMA-targeted therapy. Participants who have received targeted therapy against non-BCMA targets will not be excluded.
• Has received prior MM treatment in Arms A, B, C, and D.
Exclusion Criteria:
• Received a peripheral autologous stem cell transplant (SCT) within 12 weeks, or an allogeneic SCT within 1 year of the first dose of study drug treatment.
• Unresolved adverse event (AE)s >= Grade 2 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) from prior anticancer therapy.
• Known central nervous system involvement Multiple Myeloma (MM).
• Has any of the following conditions:
• Nonsecretory MM.
• Active Plasma cell leukemia i.e., either 20% of peripheral white blood cells or >
• 0 × 10^9L circulating plasma cells by standard differential.
• Waldenstrom's macroglobulinemia.
• Light chain amyloidosis.
• Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes (POEMS) syndrome.
• Major surgery within 4 weeks prior to first dose or planned study participation.
• Acute infections within 14 days prior to first dose of study drug requiring therapy (antibiotic, antifungal or antiviral).
• Uncontrolled diabetes or hypertension within 14 days prior to first dose.
• Peripheral neuropathy >= Grade 3 or >= Grade 2 with pain within 2 weeks prior to first dose.
• Known active infection of evidence of active hepatitis B, evidence of active hepatitis C, human immunodeficiency virus.
Drug: ABBV-383, Drug: Dexamethasone, Drug: Lenalidomide, Drug: Pomalidomide, Drug: Nirogacestat, Drug: Daratumumab
Multiple Myeloma, Relapsed/Refractory Multiple Myeloma
Relapsed/Refractory Multiple Myeloma, Pomalidomide, Dexamethasone, Lenalidomide, Daratumumab, Nirogacestat, ABBV-383, Cancer
UT Southwestern
Venetoclax in Children With Relapsed Acute Myeloid Leukemia (AML)
A study to evaluate if the randomized addition of venetoclax to a chemotherapy backbone (fludarabine/cytarabine/gemtuzumab ozogamicin [GO]) improves survival of children/adolescents/young adults with acute myeloid leukemia (AML) in 1st relapse who are unable to receive additional anthracyclines, or in 2nd relapse.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kathleen Ludwig
114894
All
29 Days to 21 Years old
Phase 3
NCT05183035
STU-2022-0725
Inclusion Criteria
• Participants must have enrolled on APAL2020SC, NCT Number: NCT04726241 prior to enrollment on ITCC-101/APAL2020D. (This is only applicable for participants in USA/Canada/Australia/New Zealand sites/LLS territory).
• Participants must be ≥ 29 days of age and ≤ 21 years of age at enrollment.
• Participants must have one of the following:
• Children, adolescents, and young adults with acute myeloid leukemia without FLT3/internal tandem duplication (ITD) mutation in:
• Second relapse, who are sufficiently fit to undergo another round of intensive chemotherapy
• First relapse who per investigator discretion cannot tolerate additional anthracycline containing chemotherapy.
• Participants must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (≥ 50% Lansky or Karnofsky score)
• Participants must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to start of protocol treatment:
• Cytotoxic chemotherapy: Must not have received cytotoxic chemotherapy within 14 days prior to start of protocol treatment, except for corticosteroids, low dose cytarabine or hydroxyurea that can be given up to 24 hours prior to start of protocol treatment.
• Intrathecal cytotoxic therapy: No wash-out time is required for participants having received any combination of intrathecal cytarabine, methotrexate, and/or hydrocortisone.
• Antibodies: ≥ 21 days must have elapsed from infusion of last dose of an antibody-drug conjugate before start of protocol treatment. For unmodified antibodies or T cell engaging antibodies, 2 half-lives must have elapsed before start of protocol treatment. Any toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
• Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors) before start of protocol treatment.
• Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or ≥7 days for short-acting growth factor before start of protocol treatment.
• Radiation therapy (RT) (before start of protocol treatment):
• ≥ 14 days have elapsed for local palliative RT (small port);
• ≥ 84 days must have elapsed if prior craniospinal RT or if ≥ 50% radiation of pelvis;
• ≥ 42 days must have elapsed if other substantial bone marrow (BM) radiation.
• Stem Cell Infusions (before start of protocol treatment):
• ≥ 84 days since allogeneic (non-autologous) bone marrow or stem cell transplant (with or without total body irradiation [TBI]) or boost infusion (any stem cell product; not including donor lymphocyte infusion [DLI])
• No evidence of active graft versus host disease (GVHD).
• Participants who are receiving cyclosporine, tacrolimus or other agents to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial. Participants must be off medications to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant for at least 14 days prior to enrollment.
• Cellular Therapy: ≥ 42 days after the completion of donor lymphocyte infusion (DLI) or any type of cellular therapy (e.g., modified T cells, natural killer [NK] cells, dendritic cells, etc.) before start of protocol treatment.
• Participants with prior exposure to venetoclax are eligible in this trial
• Adequate organ function:
• Adequate Renal Function defined as:
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 60ml/min/1.73 m^2, or
• Normal serum creatinine based on age/sex
• Adequate Liver Function defined as:
• Direct bilirubin < 1.5 x upper limit of normal (ULN), and
• Alkaline phosphatase ≤ 2.5 x ULN, and
• Serum glutamic pyruvic transaminase (SGPT) alanine aminotransferase (ALT) ≤
• 5 x ULN. If liver abnormality is due to radiographically identifiable leukemia infiltrate, the participant will remain eligible.
• Cardiac performance: Minimum cardiac function defined as:
• No history of congestive heart failure in need of medical treatment
• No pre-treatment diminished left ventricular function on echocardiography (shortening fraction [SF] < 25% or ejection fraction [EF] < 40%)
• No signs of congestive heart failure at presentation of relapse.
• Participant, parent or guardian must sign and date informed consent and pediatric assent (when required), prior to the initiation of screening or study specific procedures, according to local law and legislation. Exclusion Criteria
• Participants who in the opinion of the investigator may not be able to comply with the study requirements of the study, are not eligible.
• Participants with Down syndrome.
• Participants with Acute promyelocytic leukemia (APL) or Juvenile myelomonocytic leukemia (JMML).
• Participants with isolated CNS3 disease or symptomatic CNS3 disease.
• Participants with malabsorption syndrome or any other condition that precludes enteral administration of venetoclax.
• Participants who are currently receiving another investigational drug (GO is not considered investigational in this study).
• Participants with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known congenital bone marrow failure syndrome.
• Participants with known prior allergy to any of the medications used in protocol therapy.
• Participants with documented active, uncontrolled infection at the time of study entry.
• No known human immunodeficiency virus (HIV) infection.
• Post menarchal female participants with positive pregnancy test.
• Concomitant Medications
• Participants who have received strong and moderate CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort within 7 days of the start of study treatment.
• Participants who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days of the start of study treatment.
• Participants who have hypersensitivity to the active substance or to any of the excipients listed in summary of product characteristics (SPC).
• Pregnancy or Breast-Feeding:
• Participants who are pregnant or breast-feeding.
• Participants of reproductive potential may not participate unless they have agreed to use a highly effective contraceptive method per clinical trials facilitation group (CTFG) guidelines for the duration of study therapy and for 6 months after the completion of all study therapy.
• Male participants must use a condom during intercourse and agree not to father a child or donate sperm during therapy and for the duration of study therapy and for 4 months after the completion of all study therapy. Additional criteria to receive a gemtuzumab ozogamicin infusion: Gemtuzumab ozogamicin should not be given:
• to participants with history of veno-occlusive disease (VOD)/Sinusoidal obstruction syndrome (SOS) grade 4
• to participants with history of VOD/SOS grade 3
• to participants with CD33 negative leukemic blasts (determined at local lab) Note that these participants are eligible for the study but will not be treated with gemtuzumab ozogamicin.
• Participants must have enrolled on APAL2020SC, NCT Number: NCT04726241 prior to enrollment on ITCC-101/APAL2020D. (This is only applicable for participants in USA/Canada/Australia/New Zealand sites/LLS territory).
• Participants must be ≥ 29 days of age and ≤ 21 years of age at enrollment.
• Participants must have one of the following:
• Children, adolescents, and young adults with acute myeloid leukemia without FLT3/internal tandem duplication (ITD) mutation in:
• Second relapse, who are sufficiently fit to undergo another round of intensive chemotherapy
• First relapse who per investigator discretion cannot tolerate additional anthracycline containing chemotherapy.
• Participants must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (≥ 50% Lansky or Karnofsky score)
• Participants must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to start of protocol treatment:
• Cytotoxic chemotherapy: Must not have received cytotoxic chemotherapy within 14 days prior to start of protocol treatment, except for corticosteroids, low dose cytarabine or hydroxyurea that can be given up to 24 hours prior to start of protocol treatment.
• Intrathecal cytotoxic therapy: No wash-out time is required for participants having received any combination of intrathecal cytarabine, methotrexate, and/or hydrocortisone.
• Antibodies: ≥ 21 days must have elapsed from infusion of last dose of an antibody-drug conjugate before start of protocol treatment. For unmodified antibodies or T cell engaging antibodies, 2 half-lives must have elapsed before start of protocol treatment. Any toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
• Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors) before start of protocol treatment.
• Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or ≥7 days for short-acting growth factor before start of protocol treatment.
• Radiation therapy (RT) (before start of protocol treatment):
• ≥ 14 days have elapsed for local palliative RT (small port);
• ≥ 84 days must have elapsed if prior craniospinal RT or if ≥ 50% radiation of pelvis;
• ≥ 42 days must have elapsed if other substantial bone marrow (BM) radiation.
• Stem Cell Infusions (before start of protocol treatment):
• ≥ 84 days since allogeneic (non-autologous) bone marrow or stem cell transplant (with or without total body irradiation [TBI]) or boost infusion (any stem cell product; not including donor lymphocyte infusion [DLI])
• No evidence of active graft versus host disease (GVHD).
• Participants who are receiving cyclosporine, tacrolimus or other agents to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial. Participants must be off medications to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant for at least 14 days prior to enrollment.
• Cellular Therapy: ≥ 42 days after the completion of donor lymphocyte infusion (DLI) or any type of cellular therapy (e.g., modified T cells, natural killer [NK] cells, dendritic cells, etc.) before start of protocol treatment.
• Participants with prior exposure to venetoclax are eligible in this trial
• Adequate organ function:
• Adequate Renal Function defined as:
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 60ml/min/1.73 m^2, or
• Normal serum creatinine based on age/sex
• Adequate Liver Function defined as:
• Direct bilirubin < 1.5 x upper limit of normal (ULN), and
• Alkaline phosphatase ≤ 2.5 x ULN, and
• Serum glutamic pyruvic transaminase (SGPT) alanine aminotransferase (ALT) ≤
• 5 x ULN. If liver abnormality is due to radiographically identifiable leukemia infiltrate, the participant will remain eligible.
• Cardiac performance: Minimum cardiac function defined as:
• No history of congestive heart failure in need of medical treatment
• No pre-treatment diminished left ventricular function on echocardiography (shortening fraction [SF] < 25% or ejection fraction [EF] < 40%)
• No signs of congestive heart failure at presentation of relapse.
• Participant, parent or guardian must sign and date informed consent and pediatric assent (when required), prior to the initiation of screening or study specific procedures, according to local law and legislation. Exclusion Criteria
• Participants who in the opinion of the investigator may not be able to comply with the study requirements of the study, are not eligible.
• Participants with Down syndrome.
• Participants with Acute promyelocytic leukemia (APL) or Juvenile myelomonocytic leukemia (JMML).
• Participants with isolated CNS3 disease or symptomatic CNS3 disease.
• Participants with malabsorption syndrome or any other condition that precludes enteral administration of venetoclax.
• Participants who are currently receiving another investigational drug (GO is not considered investigational in this study).
• Participants with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known congenital bone marrow failure syndrome.
• Participants with known prior allergy to any of the medications used in protocol therapy.
• Participants with documented active, uncontrolled infection at the time of study entry.
• No known human immunodeficiency virus (HIV) infection.
• Post menarchal female participants with positive pregnancy test.
• Concomitant Medications
• Participants who have received strong and moderate CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort within 7 days of the start of study treatment.
• Participants who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days of the start of study treatment.
• Participants who have hypersensitivity to the active substance or to any of the excipients listed in summary of product characteristics (SPC).
• Pregnancy or Breast-Feeding:
• Participants who are pregnant or breast-feeding.
• Participants of reproductive potential may not participate unless they have agreed to use a highly effective contraceptive method per clinical trials facilitation group (CTFG) guidelines for the duration of study therapy and for 6 months after the completion of all study therapy.
• Male participants must use a condom during intercourse and agree not to father a child or donate sperm during therapy and for the duration of study therapy and for 4 months after the completion of all study therapy. Additional criteria to receive a gemtuzumab ozogamicin infusion: Gemtuzumab ozogamicin should not be given:
• to participants with history of veno-occlusive disease (VOD)/Sinusoidal obstruction syndrome (SOS) grade 4
• to participants with history of VOD/SOS grade 3
• to participants with CD33 negative leukemic blasts (determined at local lab) Note that these participants are eligible for the study but will not be treated with gemtuzumab ozogamicin.
Drug: Fludarabine, Drug: Cytarabine, Drug: Gemtuzumab Ozogamicin, Drug: Azacitidine, Drug: Venetoclax
Acute Myeloid Leukemia, Leukemia, Other, Leukemia, Not Otherwise Specified
Venetoclax, Gemtuzumab Ozogamicin, Fludarabine, Cytarabine, Relapsed refractory, Azacitidine
Children’s Health
A Study to Evaluate the Efficacy and Safety of Mitapivat in Pediatric Participants With Pyruvate Kinase Deficiency (PKD) Who Are Not Regularly Transfused, Followed by a 5-Year Extension Period (ACTIVATE-Kids)
Study ACTIVATE-Kids (AG348-C-023) will evaluate the efficacy and safety of orally administered mitapivat as compared with placebo in pediatric participants with pyruvate kinase deficiency (PKD) who are not regularly receiving blood transfusions. Participants will be randomized 2:1 to receive either mitapivat or matching placebo. Randomization will be stratified by age (1 to < 6 years, 6 to < 12 years, 12 to < 18 years). Participants will be dosed by age and weight during a double-blind period consisting of an 8-week dose titration period followed by a 12-week fixed-dose period. Participants who complete the double-blind period will be eligible to receive mitapivat for up to 5 years in the open-label extension (OLE) period.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Laurie.Rodgers-Augustyniak@childrens.com
Kathryn Dickerson
156007
All
1 Year to 17 Years old
Phase 3
NCT05175105
STU-2022-0452
Inclusion Criteria:
• Written informed consent from the participant, or the participant's legally authorized representative, parent(s), or legal guardian, and the participant's assent, where applicable (informed consent/assent) must be obtained before any study-related procedures are conducted, and participants must be willing to comply with all study procedures for the duration of the study;
• Aged 1 to <18 years. Participants between 12 and 24 months of age must weigh a minimum of 7 kilograms (kg);
• Clinical laboratory confirmation of pyruvate kinase deficiency (PKD), defined as documented presence of at least 2 mutant alleles in the pyruvate kinase L/R (PKLR) gene, of which at least 1 is a missense mutation, as determined per the genotyping performed by the study central genotyping laboratory;
• No more than 5 red blood cell (RBC) transfusions in the 52-week period before providing informed consent/assent and no RBC transfusions ≤12 weeks before administration of the first dose of study drug;
• Hemoglobin concentration ≤10 grams per deciliter (g/dL) for participants 12 to <18 years of age or ≤9 g/dL for participants 1 to <12 years of age during the screening period. Hb concentration must be based on an average of at least 2 Hb concentration measurements (separated by ≥7 days) collected during the screening period;
• Receiving folic acid supplementation as part of routine clinical care for at least 21 days before administration of the first dose of study drug, to be continued during study participation;
• Female participants who have attained menarche and/or breast development in Tanner Stage 2 must be abstinent of sexual activities that may induce pregnancy as part of their usual lifestyle, or agree to use 2 forms of contraception, 1 of which must be considered highly effective, from the time of informed consent/assent, throughout the study, and for 28 days after the last dose of study drug (including the time required to dose taper). The second form of contraception can include an acceptable barrier method.
Exclusion Criteria:
• Pregnant or breastfeeding;
• Homozygous for the R479H mutation or have 2 nonmissense mutations, without the presence of another missense mutation, in the PKLR gene as determined per the genotyping performed by the study central genotyping laboratory;
• History of malignancy;
• History of active and/or uncontrolled cardiac or pulmonary disease or clinically relevant QT prolongation within 6 months before providing informed consent/assent;
• Hepatobiliary disorders including, but not limited to:
• Liver disease with histopathological evidence of cirrhosis or severe fibrosis;
• Clinically symptomatic cholelithiasis or cholecystitis (participants with prior cholecystectomy are eligible);
• History of drug-induced cholestatic hepatitis;
• Aspartate aminotransferase >2.5×upper limit of normal (ULN) (unless due to hemolysis and/or hepatic iron deposition) and alanine aminotransferase >2.5×ULN (unless due to hepatic iron deposition);
• Renal dysfunction as defined by an estimated glomerular filtration rate <60 milliliters per minute (mL/min)/1.73 m^2;
• Nonfasting triglycerides >440 milligrams per deciliter (mg/dL) (5 millimoles per liter [mmol/L]);
• Active uncontrolled infection requiring systemic antimicrobial therapy;
• Participants with known active hepatitis B or hepatitis C virus infection;
• Participants with known human immunodeficiency virus (HIV) infection;
• History of major surgery (including splenectomy) ≤6 months before providing informed consent/assent and/or planning on undergoing a major surgical procedure during the screening or double-blind period;
• Current enrollment or past participation (within 90 days before the first dose of study drug or a time frame equivalent to 5 half-lives of the investigational study drug, whichever is longer) in any other clinical study involving an investigational study drug or device;
• Prior exposure to gene therapy, or bone marrow or stem cell transplantation;
• Currently receiving hematopoietic stimulating agents; the last dose must have been administered at least 28 days or a time frame equivalent to 5 half-lives (whichever is longer) before randomization;
• Receiving products that are strong inhibitors of CYP3A4/5 that have not been stopped for ≥5 days or a time frame equivalent to 5 half-lives (whichever is longer), or strong inducers of CYP3A4 that have not been stopped for ≥28 days or a time frame equivalent to 5 half-lives (whichever is longer), before randomization;
• Receiving anabolic steroids, including testosterone preparations, that have not been stopped for at least 28 days before randomization;
• Known allergy, or other contraindication, to mitapivat or its excipients (microcrystalline cellulose, croscarmellose sodium, sodium stearyl fumarate, mannitol, Opadry® II Blue [hypromellose, titanium dioxide, lactose monohydrate, triacetin, and Food, Drug, and Cosmetics blue dye number 2 (FD&C Blue #2)], Opadry® II White [hypromellose, titanium dioxide, lactose monohydrate, and triacetin], and magnesium stearate);
• Any medical, hematologic, psychological, or behavioral condition(s) or prior or current therapy that, in the opinion of the Investigator, may confer an unacceptable risk to participating in the study and/or could confound the interpretation of the study data; also included are:
• Participants who are institutionalized by regulatory or court order.
• Participants with any condition(s) that could create undue influence (including but not limited to incarceration, involuntary psychiatric confinement, and financial or familial affiliation with the Investigator or Sponsor).
• Receiving a pyruvate kinase activator that has not been stopped for ≥52 weeks before providing informed consent/assent.
Drug: Mitapivat, Drug: Mitapivat-matching placebo
Pediatric Pyruvate Kinase Deficiency, Pediatric Hemolytic Anemia
Anemia, Hematologic Diseases, Metabolic Diseases, Mitapivat, AG-348, ACTIVATE-Kids, PK Deficiency
Children’s Health
Pediatric Radiation Oncology With Movie Induced Sedation Effect (PROMISE)
PROMISE (Pediatric Radiation Oncology with Movie Induced Sedation Effect) is an interactive incentive-based movie system that integrates with a video surveillance gating module (VisionRT) as an alternative sedation solution for pediatric patients undergoing radiation treatment (RT). This single-arm, open label, single-center phase II clinical trial is to implement PROMISE for all children ages 3-11 who are planned to undergo RT at the institution. The primary goal is to decrease the total number of pediatric patients who require general anesthesia through the use of PROMISE, with secondary goals being to assess the impact that PROMISE has on patient/family anxiety and quality of life, treatment time and clinical efficiency, and overall cost. The investigators hypothesize that PROMISE will lead to a reduction in the percentage of patients ages 3-7 who require general anesthesia use from 70% (historical control) to 30%.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kiran Kumar
181795
All
3 Years to 11 Years old
Phase 2
NCT05148078
STU-2021-1005
Inclusion Criteria:
• Planned to undergo radiation treatment
• Age 3-11 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at screening
• Parents or guardians with the ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
• Subjects with documented medical behavior conditions or other conditions necessitating anesthesia use
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects whose parents opt to not include them (the subject) in the clinical trial.
Other: PROMISE (Pediatric Radiation Oncology with Movie Induced Sedation Effect)
Multiple Myeloma, Pediatric Cancer, Brain and Nervous System, Eye and Orbit, Bones and Joints, Kidney, Lip, Oral Cavity and Pharynx, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Rectum, Thyroid, Leukemia, Other, Leukemia, Not Otherwise Specified, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Non-Hodgkins Lymphoma, Other Hematopoietic, Soft Tissue
radiotherapy
UT Southwestern; Children’s Health
Phase 1/2a Study of Belantamab Mafodotin in Relapsed or Refractory AL Amyloidosis
This study evaluates the safety, tolerability, recommended phase II (RP2) dose, and efficacy of Belantamab mafodotin for participants with Relapsed Refractory AL Amyloidosis (RRAL.)
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Larry Anderson
102991
All
18 Years and over
Phase 1/Phase 2
NCT05145816
STU-2021-0952
Inclusion Criteria:
• Participants medically diagnosed with relapsed or refractory Amyloid Light Chain Amyloidosis (AL amyloidosis) with more than one line of treatment as below:
• Must have received a proteosome inhibitor, alkylator and anti-cluster of differentiation 38 (CD38) antibody (e.g., daratumumab - for patients who were eligible to receive in newly diagnosed AL Amyloidosis) and autologous stem cell transplant (for transplant eligible candidates). And
• Failed treatment and/or intolerant/ineligible for above agents
• Patients who fail to achieve Partial Hematological Response or better after 2 cycles of induction therapy for newly diagnosed AL Amyloidosis are also eligible.
• Participant must be over 18 years of age inclusive, at the time of signing the informed consent.
• Participant and Disease Characteristics: Patient must have primary systemic AL amyloidosis, histologically confirmed at the initial diagnosis before initiation of 1st-line treatment by positive Congo red stain with green birefringence on polarized light microscopy, Or characteristic appearance by electron microscopy AND confirmatory AL amyloid typing (mass spectrometry-based proteomic analysis or immunofluorescence).
• Patient must have measurable disease within 28 days prior to registration; serum quantitative immunoglobulins (immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM), serum free kappa and lambda, and serum protein electrophoresis (SPEP) with M-protein quantification must be obtained within 14 days prior to registration.
• Measurable disease of amyloid light chain amyloidosis as defined by at least One of the following:
• Serum M-protein ≥0.5 g/dL by protein electrophoresis (routine serum protein electrophoresis and immunofixation).
• Serum free light chain ≥50 mg/L with an abnormal kappa: lambda ratio or the difference between the involved and uninvolved free light chains (dFLC) ≥50 mg/L.
• One or more organs impacted by AL Amyloidosis according to consensus guidelines below per National Comprehensive Cancer Network (NCCN)Guidelines Version 1.2016: a. Cardiac Involvement i. Mean left ventricular wall thickness on echocardiogram greater than or equal to 12 mm in the absence of hypertension or valvular heart disease, OR N-terminal fragment brain natriuretic protein (NT-pro) brain natriuretic peptide (BNP) greater than 332 ng/mL provided that patient does not have impaired renal function (as defined by calculated creatinine clearance less than 25 mL/min) within 14 days prior to registration, OR prior cardiac biopsy (at time of diagnosis) showing amyloid deposition with past documented or presently noted clinical symptoms and signs supportive of a diagnosis of heart failure in the absence of an alternative explanation for heart failure. b. Non-Cardiac Organ Involvement i. Kidney: albuminuria greater than or equal to 500 mg per day on a 24-hour urine specimen within 35 days prior to registration, OR prior kidney biopsy (at the time of diagnosis) showing amyloid deposition. ii. Liver: hepatomegaly (total liver span > 15 cm) as demonstrated by computed tomography (CT) or magnetic resonance imaging (MRI) within 35 days prior to registration OR alkaline phosphatase (ALP) greater than 1.5 times the institutional upper limit of normal within 14 days prior to registration, OR prior liver biopsy (at the time of diagnosis) showing amyloid deposition. iii. Gastrointestinal tract: direct biopsy verification with symptoms. iv. Lung: biopsy verifications with symptoms and interstitial radiographic pattern. v. Soft tissue: tongue enlargement, clinical, arthropathy, claudication, presumed vascular amyloid, skin involvement, carpal tunnel syndrome, myopathy by biopsy or pseudohypertrophy.
• Patients must have completed other systemic therapy or investigational drug > 28 days or five half-lives prior to registration, surgery (other than biopsies) > 28 days prior to registration, and any autologous stem cell transplant (ASCT) > 100 days prior to registration.
• Patients must have a complete medical history and physical exam within 14 days prior to registration.
• New York Heart Association (NYHA) Class 1 - 3a which has been clinically stable for 56 days before registration
• Eastern Cooperative Oncology Group (ECOG) performance score 0, 1 or 2
• Left ventricular ejection fraction (LVEF) by echocardiogram (ECHO) > 35% within 28 days prior to registration.
• Adequate organ system functions within 14 days of registration as defined by the laboratory assessments below: a) Hematologic i) Absolute neutrophil count (ANC): ≥1.0 × 109/ L * ii) Hemoglobin: ≥8.0 g/dL * iii) Platelets: ≥50 × 109/L * b) Hepatic i) Total bilirubin: 1.5 × upper limit of normal (ULN); (Isolated bilirubin ≥1.5 × ULN is acceptable if bilirubin is fractionated, and direct bilirubin is <35%) ii) Alanine aminotransferase (ALT): ≤2.5 × ULN c) Renal i) Estimated glomerular rate (eGFRª): ≥30 mL/min/1.73 m2 Note: Laboratory results obtained during Screening should be used to determine eligibility criteria. In situations where laboratory results are outside the permitted range, the investigator may re-test the participant and the subsequent within range screening result may be used to confirm eligibility. * Without growth factor or cell transfusion support for the past 14 days prior to testing, excluding erythropoietin. ª As calculated by Modified Diet in Renal Disease (MDRD) formula (Appendix 4 in Protocol)
• Females of childbearing potential: These participants must have a negative baseline pregnancy test within 72 hours prior to registration; this may be either a serum or urine pregnancy test, with a sensitivity of at least 50 milli-International unit (mIU)/mL; females of childbearing potential must also agree: (1) to have a pregnancy test prior to the start of each treatment cycle and (2) to either commit to continued abstinence from heterosexual intercourse or to use effective contraception while receiving study drug and for at least 4 months after receiving the last dose of study drug; females are considered to be of childbearing potential if they have had menses at any time in the preceding 24 consecutive months; in addition to routine contraceptive methods, effective contraception also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, she is responsible for beginning contraceptive measures.
• Is a woman of child bearing potential (WOCBP) and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency (as described in Appendix 9), during the intervention period and for at least 4 months after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
• A WOCBP must have a negative serum pregnancy test (as required by local regulations) within 72 hours before the first dose of study intervention.
• The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with a nearly undetected pregnancy.
• Non-childbearing potential is defined as follows (by other than medical reasons): i. ≥45 years of age and has not had menses for >1 year. ii. Patients who have been amenorrhoeic for <2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation. iii. Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure.
• Male participants are eligible to participate if they agree to the following during the intervention period and for 6 months after the last dose of study treatment to allow for clearance of any altered sperm:
• Refrain from donating sperm Plus, either:
• be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent Or
• agree to use a barrier method of birth control (e.g., male condom), even if they have undergone a successful vasectomy, and female partner to use an additional highly effective contraceptive method with a failure rate of <1% per year as when having sexual intercourse with a woman of childbearing potential (including pregnant females).
• Patients with Human Immunodeficiency Virus (HIV) infection are eligible if:
• patients without a history of Acquired Immune Deficiency Syndrome (AIDS)-defining opportunistic infections
• patients with a history of AIDS-defining opportunistic infection may be eligible if they have not had an opportunistic infection within past 12 months.
• Patients on active anti-retroviral therapy are eligible as long as anti-retroviral therapy is established for at least four weeks and have HIV viral load less than 400 copies/ml prior to enrollment.
• Patients with chronic Hepatitis B Virus (HBV) infection or chronic Hepatitis C Virus (HCV) infection or virologically suppressed on HCV treatment are eligible if:
• Hepatitis B surface antigen (HBsAg)-negative, anti-Hemoglobin C (HBc)-positive patients are at lower risk of HBV reactivation compared with HBsAg-positive patients, risk of HBV reactivation should be considered in all patients and if patients can be on anti-HBV prophylaxis prior to initiation of anti-cancer therapy.
• Patients with chronic HBV infection with active disease who meet the criteria for anti HBV therapy should be on a suppressive antiviral therapy prior to initiation of cancer therapy.
• Patients actively on treatment for HCV should have HCV below the limit of quantification before initiation of anti-cancer therapy.
• Patients who are HCV antibody (Ab) positive but HCV Ribonucleic Acid (RNA) negative due to prior treatment or natural resolution of infection are eligible.
Exclusion Criteria:
• Patients previously treated for active symptomatic multiple myeloma.
• Any corneal disease except for mild epithelial punctate keratopathy.
• Patients with known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to belantamab mafodotin or drugs chemically related to belantamab mafodotin, or any of the components of the study treatment.
• Patients eligible for autologous stem cell transplantation (ASCT).
• Evidence of significant cardiovascular condition as specified below:
• N-terminal-prohormone of brain natriuretic peptide (NT-proBNP) ≥ 8500ng/L within 14 days of registration.
• New York Heart Association (NYHA) classification IIIB (3b) through IV (4) heart failure
• Heart failure that in the opinion of the investigator is on the basis of ischemic heart disease (e.g., prior myocardial infarction with documented history of cardiac enzyme elevation and electrocardiogram (ECG) changes) or uncorrected valvular disease and not primarily due to AL amyloid cardiomyopathy
• Unstable heart failure defined as emergency hospitalization for worsening, or decompensated heart failure, or syncopal episode within 1 month of screening
• Subjects with a history of sustained ventricular tachycardia or aborted ventricular fibrillation or with a history of atrioventricular nodal or sinoatrial (SA) nodal dysfunction for which a pacemaker/implantable cardioverter-defibrillator (ICD) is indicated but not placed (Subjects who do have a pacemaker/ICD are allowed on study)
• Interval from the Q wave on the ECG to point T using Fredericia's formula (QTcF) > 500 msec. Subjects who have a pacemaker may be included regardless of calculated QTc interval
• Symptomatic, clinically significant autonomic neuropathy which the Investigator feels will preclude administration of study treatment
• Acute coronary syndrome, or any form of coronary revascularization procedure including coronary artery bypass grafting (CABG), within 6 months of screening
• Prior solid organ transplant, or anticipated to undergo solid organ transplantation, or requiring left ventricular assist device (LVAD) implantation, during the course of the study
• Stroke within 6 months of screening, or transient ischemic attack (TIA) within 3 months of screening
• Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Mobitz Type II) or 3rd degree atrioventricular (AV) block
• History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within three (3) months of Screening
• Uncontrolled hypertension
• Prior history of malignancy with the exception of the following: adequately treated basal cell or squamous cell skin cancer, curatively treated non-melanoma skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for at least two years.
• Presence of any comorbid or uncontrolled medical condition (e.g., diabetes mellitus or uncontrolled hypertension) at screening, which in the opinion of the investigator would increase the potential risk to the subject.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 4 weeks or five half-lives, whichever is shorter, before Cycle 1 Day 1.
• Participant must not use contact lenses while participating in this study.
• Participant must not have had major surgery ≤ 4 weeks prior to initiating study treatment.
• Participant must not have any evidence of active mucosal or internal bleeding.
• Participant must not have any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormalities) that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures.
• Participants must not be pregnant or lactating.
• Participant must not be simultaneously enrolled in any interventional clinical trial.
• Participant must not have an active infection requiring treatment.
• Participant must not have current unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Note: Stable non-cirrhotic chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if otherwise meets entry criteria.
Drug: Belantamab mafodotin 2.5 mg/kg (8 weeks), Drug: Belantamab mafodotin 1.9 mg/kg (8 weeks), Drug: Belantamab mafodotin 1.4 mg/kg (12 weeks), Drug: Belantamab mafodotin 1.9 mg/kg (12 weeks), Drug: Belantamab mafodotin every 4 weeks, 6 weeks,8 weeks, or 12 weeks as determined by Part 1 recommended dosages, Drug: Belantamab mafodotin 1.0 mg/kg (12 weeks)
Multiple Myeloma, Amyloidosis, AL Amyloidosis
UT Southwestern
Caloric Restriction and Activity to Reduce Chemoresistance in B-ALL (IDEAL2)
This study is for older children, adolescents, and young adults with B-cell Acute Lymphoblastic Leukemia (B-ALL). Higher amounts of body fat is associated with resistance to chemotherapy in patients with B-ALL. Chemotherapy during the first month causes large gains in body fat in most people, even those who start chemotherapy at a healthy weight. This study is being done to find out if caloric restriction achieved by a personalized nutritional menu and exercise plan during routine chemotherapy can make the patient's ALL more sensitive to chemotherapy and also reduce the amount of body fat gained during treatment. The goals of this study are to help make chemotherapy more effective in treating the patient's leukemia as demonstrated by fewer patients with leukemia minimal residual disease (MRD) while also trying to reduce the amount of body fat that chemotherapy causes the patient to gain in the first month.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
67555
All
10 Years to 25 Years old
Phase 2
NCT05082519
STU-2022-0479
Inclusion Criteria:
• Patients must be ≥ 10.0 and <26.0 years of age.
• Patients must have a diagnosis of de novo B-ALL
• Patients must have a M3 marrow (>25% blasts by morphology) or at least 1,000/µL circulating leukemia cells in PB confirmed by Flow Cytometry (or other convincing evidence of a B-ALL diagnosis not meeting above criteria following central review by the Study Hematopathologist and Study Chair or Vice-Chair).
• The treatment regimen must be the first treatment attempt for B-ALL-
• Must be a multi-agent induction regimen inclusive of vincristine, glucocorticoid, pegaspargase/calaspargase, and daunorubicin or doxorubicin and with a planned duration <35 days.
• Organ function must meet that required for initiation of chemotherapy
• Patients at diagnosis must meet Karnofsky > 50% for patients > 16 years of age and Lansky > 50% for patients ≤ 16 years of age (or be expected to recover prior to Day 8) .
• If the patient is a female of childbearing potential, a negative urine or serum pregnancy test is required within two weeks prior to enrollment.
Exclusion Criteria:
• Patient will be excluded if they are underweight at time of enrollment (BMI% <5th percentile for age for patients age 10-19 years, BMI <18.5 in patients 20-29 years).
• Patients with Down syndrome or a DNA fragility syndrome (such as Fanconi anemia, Bloom syndrome) will be excluded.
• Patient receiving a SJCRH-style "Total Therapy" regimen will be excluded.
• Patients receiving anti-CD20 monoclonal antibody therapy during induction therapy.
• Patients will be excluded if they received treatment for a previous malignancy.
• Patient will be excluded if they are pregnant.
• Patient will be excluded if they have a pre-diagnosis requirement for enteral or parenteral supplementation .
• Patient will be excluded due to inability to perform the intervention (e.g., specific nutritional needs, severe developmental delay, paraplegia)
• Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results
Behavioral: IDEAL2 Intervention
Obesity, B-cell Acute Lymphoblastic Leukemia, Lymphoid Leukemia
obesity, leukemia, B-cell leukemia, Pediatric obesity, Pediatric ALL
Children’s Health
CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma
This phase I/II trial evaluates the best dose, side effects and possible benefit of CBL0137 in treating patients with solid tumors, including central nervous system (CNS) tumors or lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Drugs, such as CBL0137, block signals passed from one molecule to another inside a cell. Blocking these signals can affect many functions of the cell, including cell division and cell death, and may kill cancer cells.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Laura Klesse
13954
All
12 Months to 30 Years old
Phase 1/Phase 2
NCT04870944
STU-2023-0600
Inclusion Criteria:
• Parts A and B1: Patients must be >= 12 months and =< 21 years of age at the time of study enrollment
• Part B2 (relapsed/refractory osteosarcoma): Patients must be >= 12 months and =< 30 years of age at the time of study enrollment
• Patients must have had histologic verification of malignancy at original diagnosis or relapse, except in patients with diffuse intrinsic brain stem tumors, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers, including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
• Part A: Patients with relapsed or refractory solid tumors or lymphoma, including patients with CNS tumors or known CNS metastases (including untreated or progressive) are eligible
• Part B1: Patients with progressive or recurrent DIPG (diagnosed by biopsy or imaging characteristics) and other H3 K27M-mutant diffuse midline gliomas previously treated with radiation therapy
• Part B2: Patients with relapsed or refractory osteosarcoma
• Part A: Patients must have either measurable or evaluable disease
• Part B1 and B2: Patients must have measurable disease
• Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
• Patients must have a performance status corresponding to Easter Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age. Patients must have a Karnofsky or Lansky score >= 50%
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive
• Solid tumor patients: >= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (eg, not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid. Patients with CNS tumors receiving corticosteroids must have been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
• Stem cell Infusions (with or without total body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 30 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• Radiation therapy [XRT]/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, I-131 metaiodobenzylguanidine [131I MIBG]): >= 42 days after systemically administered radiopharmaceutical therapy
• Patients must not have received prior exposure to CBL0137
• For patients with solid tumors without known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/uL (performed within 7 days prior to enrollment unless otherwise indicated)
• Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
• For patients with solid tumors without known bone marrow involvement:
• Platelet count >= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (performed within 7 days prior to enrollment unless otherwise indicated)
• Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a creatinine based on age/gender as follows (performed within 7 days prior to enrollment unless otherwise indicated):
• Age: Maximum serum creatinine (mg/dL)
• 1 to < 2 years: 0.6 (male); 0.6 (female)
• 2 to < 6 years: 0.8 (male); 0.8 (female)
• 6 to < 10 years: 1 (male); 1 (female)
• 10 to < 13 years: 1.2 (male); 1.2 (female)
• 13 to < 16 years: 1.5 (male); 1.4 (female)
• >= 16 years: 1.7 (male); 1.4 (female)
• Patients with solid tumors:
• Bilirubin (sum of conjugated + unconjugated or total) =< 1.5 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment unless otherwise indicated)
• Patients with solid tumors:
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L (performed within 7 days prior to enrollment unless otherwise indicated)
• Shortening fraction of >= 27% by echocardiogram (performed within 7 days prior to enrollment unless otherwise indicated)
• Ejection fraction of >= 50% by gated radionuclide study (performed within 7 days prior to enrollment unless otherwise indicated)
• Corrected QT (QTC) < 480 msec (performed within 7 days prior to enrollment unless otherwise indicated)
• Patients with seizure disorder may be enrolled if seizures well controlled without the use of enzyme-inducing anti-convulsant agents. Well controlled is defined by no increase in seizure frequency in the prior 7 days
• Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] version [v]5) resulting from prior therapy must be =< grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible
• Patients have consented to receive a central venous catheter prior to the administration of CBL0137. A central line is required for CBL0137 administration
Exclusion Criteria:
• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control
• Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Patients who are currently receiving another investigational drug are not eligible
• Patients who are currently receiving other anti-cancer agents are not eligible (except leukemia patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy)
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
• Patients who are receiving drugs that are strong inducers or inhibitors of CYP3A4, CYP2B6 (e.g., carbamazepine) and CYP1A2 (e.g., ciprofloxacin, enoxacin, fluvoxamine, smoking) are not eligible. These agents are to be avoided for 7 days prior to the start of CBL0137 and for the duration of the protocol therapy. Sensitive substrates of CYP2D6 (e.g., atomoxetine, desipramine, dextromethorphan, eliglustat, nebivolol, nortriptyline, perphenazine, tolterodine, R-venlafaxine) should also be avoided for the duration protocol therapy
• Patients who are receiving drugs associated with a known risk of Torsades de Pointes (TdP) are not eligible. Drugs associated with known risk of Torsades de Pointes (TdP) are to be avoided for 7 days prior to the start of CBL0137 and for duration of the protocol therapy
• Patients with known peripheral vascular disease are excluded
• Patients with a history of pro-thrombotic disorder are not eligible
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspirate, Procedure: Bone Marrow Biopsy, Procedure: Echocardiography, Drug: FACT Complex-targeting Curaxin CBL0137
Lymphoma, Recurrent Osteosarcoma, Recurrent Malignant Solid Neoplasm, Recurrent Lymphoma, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Osteosarcoma, Recurrent Primary Malignant Central Nervous System Neoplasm, Refractory Primary Malignant Central Nervous System Neoplasm, Brain and Nervous System, Bones and Joints, Diffuse Midline Glioma, H3 K27M-Mutant, Metastatic Malignant Neoplasm in the Central Nervous System, Recurrent Diffuse Intrinsic Pontine Glioma
Children’s Health
VITAS: Atezolizumab in Combination With Chemotherapy for Pediatric Relapsed/Refractory Solid Tumors
This trial is a multi-center, non-randomized, open-label Phase I/II study evaluating the feasibility and efficacy of vincristine, irinotecan, temozolomide, and atezolizumab in children with relapsed/refractory solid tumors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Matthew Campbell
108757
All
6 Months to 18 Years old
Phase 1/Phase 2
NCT04796012
STU-2021-0606
Inclusion Criteria:
• Signed informed consent
• Relapsed or refractory solid tumor after at least one prior course of therapy.
• Hodgkin lymphoma or non-Hodgkin lymphoma are not permitted.
• Patients with CNS malignancy or asymptomatic CNS metastases may be enrolled, provided all of the following criteria are met.
• No metastatic or primary disease affecting the brainstem, midbrain, pons, or cerebellum, or within 10 mm of optic nerve
• No history of leptomeningeal disease
• No history of intracranial or spinal cord hemorrhage
• No evidence of progression of neurologic deficit, in the investigator's judgment, within 7 days prior to initiation of study medications.
• Must have histologically confirmed rhabdomyosarcoma (RMS) for RMS efficacy cohort.
• Age ≥ 6 months and ≤ 18 years
• Lansky Performance Status (patients < 16 years old) or Karnofsky Performance Status (patients ≥ 16 years old) ≥ 50
• Ability to comply with the study protocol, in the investigator's judgment
• For RMS efficacy cohort, disease must be measurable as defined by RECIST v1.1.
• For the feasibility cohort, disease must be evaluable, but patients enrolled in the feasibility cohort will be prospectively assessed for measurable disease, RMS patients will also be included in the RMS efficacy cohort.
• Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation.
• Availability of a tumor specimen suitable for determination of PD-L1 status, either from initial diagnosis or from a recurrence.
• For PD-L1 staining to be performed at the central site, a formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 15 slides containing unstained, freshly cut, serial sections must be available along with an associated pathology report prior to study enrollment.
• Patients for whom the required number of slides are not available may still be eligible to enroll on study with PI approval
• For the RMS efficacy cohort, it will be required that at least 8 of 17 patients have PD-L1(+) tumor. PD-L1 status will be determined at time of enrollment for all patients. When the maximum allowable number of PD-L1(-) patients has been enrolled and treated on study, PD-L1 positivity will be required for all further enrolled patients.
• Staining will be performed in the central site CAP/CLIA-certified laboratory using the 22c3 antibody for immunohistochemical analysis
• PD-L1(+) status will be defined as staining on ≥1% of tumor cells or ≥1% of stroma.
• For the feasibility cohort, PD-L1 positivity is not required but will be performed centrally in all cases for exploratory biomarker studies.
• Adequate organ and marrow function as defined by the following laboratory values obtained within 21 days prior to initiation of study medication.
• For patients without known bone marrow involvement:
• Absolute neutrophil count ≥ 1.0 x 10^9 / L (1000/µL) without granulocyte colony-stimulating factor support (≥14 days after the last dose of a long-acting growth factor such as pegfilgrastim, or 7 days after short-acting growth factor)
• Absolute lymphocyte count ≥ 0.5 x 10^9 / L (500/µL)
• Platelet count ≥ 75 x 10^9 / L (75,000/µL) without transfusion in the last 7 days
• Patients with known bone marrow metastatic disease will be eligible for the study if they meet the following criteria:
• Patients with documented liver metastases: AST and ALT ≤ 5 x ULN
• Patients with documented liver or bone metastases: ALP ≤ 5 x ULN
• Absolute neutrophil count (ANC) ≥ 750/mm^3
• Absolute lymphocyte count ≥ 0.4 x 10^9 / L (400/µL)
• Platelet count ≥ 50,000/mm^3 (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions)
• These patients will not be evaluable for hematologic toxicity. At least 4 of 6 patients in the feasibility cohort must be evaluable for hematologic toxicity. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity.
• Total bilirubin ≤1.5 x upper limit of normal (ULN) for age (Patients with known Gilbert disease: serum bilirubin ≤ 3 x ULN)
• AST (SGOT) and ALT (SPGT) ≤ 2.5 x ULN for age
• Serum albumin ≥ 25 g/L (2.5 g/dL)
• Creatinine ≤ 1.5 x ULN for age or creatinine clearance (or radioisotope glomerular filtration rate) ≥ 70 mL/min/1.73 m2
• Left ventricular ejection fraction ≥ 50% or shortening fraction ≥ 30%
• Hemoglobin ≥ 90 g/L (9 g/dL)
• Patients may be transfused to meet this criterion.
• For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN
• For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
• Negative HIV and hepatitis B surface antigen (HBsAg) tests at screening
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as defined below:
• Women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 5 months after the final doses of atezolizumab, vincristine, and temozolomide. Women must refrain from donating eggs during this same period.
• A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus), regardless of sexual orientation or marital status.
• Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
• The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception.
• For men who are not surgically sterile: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:
• With a female partner of childbearing potential who is not pregnant, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of less 1% per year during the treatment period and for 5 months after the final doses of atezolizumab, irinotecan, and temozolomide. Men must refrain from donating sperm during this same period.
• The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception
Exclusion Criteria:
• Pregnancy or breast-feeding:
• Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of study treatment
• Women of childbearing potential must have a negative serum pregnancy test result within 21 days prior to initiation of study treatment.
• Medical conditions that are excluded:
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Guillain-Barré syndrome, multiple sclerosis, or Kawasaki syndrome with the following exceptions:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
• Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met at study initiation: (1) Rash must cover less 10% of body surface area, (2) Disease is well controlled at baseline and requires only low-potency topical corticosteroids, (3) No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
• Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected serum calcium > ULN)
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• Patients with indwelling catheters (e.g., PleurX®) are allowed.
• Uncontrolled tumor-related pain
• Patients requiring pain medication must be on a stable regimen at study entry for at least 2 weeks. Intermittent use of as-needed medication is allowed during this period.
• Clinically significant gastrointestinal disorder that may interfere with absorption of orally administered drugs (at the discretion of the treating physician)
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
• History of severe asthma or uncontrolled asthma
• Dyspnea at rest or requirement for supplemental oxygen
• Uncontrolled seizures. Patients taking a stable dose of anticonvulsants (for 2 weeks) are permitted, as long as they are not strong inducers or inhibitors of CYP3A4.
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications in the opinion of the treating investigator
• Washout periods from prior therapies:
• Myelosuppressive chemotherapy or radiotherapy within 21 days prior to starting study treatment.
• Subjects must have recovered from all acute prior treatment-related toxicities to grade 1 or baseline (excluding alopecia and clinically stable toxicities requiring ongoing medical management, such as hypothyroidism).
• Non-myelosuppressive cancer therapy, such as kinase inhibitors, within 7 days prior to study treatment.
• Treatment with monoclonal antibodies with long half-lives, within 3 half-lives prior to study treatment.
• Treatment with targeted cellular therapies within 28 days prior to starting study treatment.
• Major surgical procedure, other than for diagnosis, within 30 days prior to initiation of study treatment, or anticipation of the need for a major surgical procedure during the first four cycles of the study.
• Biopsy tissue collection or placement of a vascular access device is permitted if the site has healed prior to initiation of study medications.
• For patients with CNS disease, no neurosurgical resection, brain biopsy, or stereotactic/whole-brain radiation within 30 days prior to Cycle 1, Day 1
• Treatment with a live, attenuated vaccine within 30 days prior to initiation of study treatment, or anticipation of the need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
• Treatment with investigational therapy within 21 days prior to initiation of study treatment or concurrent participation with another investigational agent
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-agents) within 2 weeks prior to initiation of study treatment, or anticipation of the need for systemic immunosuppressive medication during study treatment, with the following exceptions:
• Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after Principal Investigator confirmation has been obtained.
• Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
• Patients with CNS disease can be receiving concurrent treatment with corticosteroids with approval from the Principal Investigator. Patients must be receiving a stable or decreasing dose for ≥ 5 days prior to the baseline MRI scan and at the time of drug initiation. The Principal Investigator should be informed when steroid doses are increased because of declining patient status.
• Use of strong CYP3A4 inhibitors or inducers or strong UGT1A1 inhibitors within 12 days of Cycle 1, Day 1.
• Treatment with high-dose chemotherapy and hematopoietic stem-cell rescue within 3 months prior to initiation of study drug
• Treatment with herbal cancer therapy within 1 week prior to initiation of study medications.
• Treatment with a long-acting hematopoietic growth factor (such as pegfilgrastim) within 2 weeks prior to initiation of study medications, or a short-acting hematopoietic growth factor (such as G-CSF) within 1 week prior to initiation of study medications.
• Prior treatments:
• Prior allogeneic stem cell or solid organ transplantation
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies to include all anti-PD-1, and anti-PD-L1 therapeutic antibodies
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2] within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
• Subjects must not have previously progressed while receiving regimens that include irinotecan or temozolomide. Patients who have received irinotecan or temozolomide and did not progress while on these medications are eligible.
• Known ongoing or untreated infection, including, but not limited to bacteremia, active tuberculosis, or severe pneumonia
• Active tuberculosis
• Current treatment with anti-viral therapy for HBV
• Active hepatitis C
• Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study
• Known allergy or hypersensitivity to any component of the study medications
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
Drug: Atezolizumab, Drug: Vincristine, Drug: Irinotecan, Drug: Temozolomide
Lymphoma, Rhabdomyosarcoma, Solid Tumor, Brain and Nervous System, Colon, Soft Tissue
Relapsed solid tumor, Refractory solid tumor, Rhabdomyosarcoma
UT Southwestern; Children’s Health
Efficacy and Safety of Nemtabrutinib (MK-1026) in Participants With Hematologic Malignancies (MK-1026-003)
The purpose of this study is to evaluate the safety and efficacy of nemtabrutinib (formerly ARQ 531) in participants with hematologic malignancies of chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), Richter's transformation, marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and Waldenström's macroglobulinemia (WM).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Farrukh Awan
180091
All
18 Years and over
Phase 2
NCT04728893
STU-2023-0815
Inclusion Criteria:
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7 days prior to allocation
• Has a life expectancy of at least 3 months, based on the investigator assessment
• Has the ability to swallow and retain oral medication
• Participants who are Hepatitis B surface antigen (HBsAg)-positive are eligible if they have received Hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization
• Participants with history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
• Has adequate organ function
• Male participants agree to refrain from donating sperm and agree to either remain abstinent from penile-vaginal intercourse as their preferred and usual lifestyle OR agree to use contraception, during the intervention period and for at least the time required to eliminate the study intervention after last dose of study intervention
• Female participants assigned female sex at birth who are not pregnant or breastfeeding are eligible to participate if not a participant of childbearing potential (POCBP), or if a POCBP they either use a contraceptive method that is highly effective OR remain abstinent from penile-vaginal intercourse as their preferred and usual lifestyle during the intervention period and for at least 30 days after the last dose of study intervention
• Participants with HIV are eligible if they meet all of the following: the CD4 count is >350 cells/uL at screening, the HIV viral load is below the detectable level, are on a stable ART regimen for at least 4 weeks prior to study entry, and are compliant with their ART Part 1 and Part 2 (Cohorts A to C)
• Has a confirmed diagnosis of CLL/SLL with
• At least 2 lines of prior therapy (Part 1 only)
• Part 2 Cohort A: CLL/SLL participants who are relapsed or refractory to prior therapy with a covalent, irreversible Bruton's tyrosine kinase inhibitor (BTKi), and a B-cell lymphoma 2 inhibitor (BCL2i). CLL participants must have received and failed, been intolerant to, or determined by their treating physician to be a poor phosphoinositide 3-kinase inhibitor (PI3Ki) candidate or ineligible for a PI3Ki per local guidelines
• Part 2 Cohort B: CLL/SLL participants who are relapsed or refractory following at least 1 line of prior therapy and are BTKi treatment naive
• Part 2 Cohort C: CLL/SLL participants with 17p deletion or tumor protein p53 (TP53) mutation who are relapsed or refractory following at least 1 line of prior therapy
• Has active disease for CLL/SLL clearly documented to initiate therapy
• Has evaluable core or excisional lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy or bone marrow aspirate at Screening (optional for participants enrolling in Part 1) Part 2 (Cohorts D to G)
• Has a confirmed diagnosis of and response to previous treatment of one of the following:
• Participants with Richter's transformation who are relapsed or refractory following at least 1 line of prior therapy (Cohort D)
• Participants with pathologically confirmed MCL, documented by either overexpression of cyclin D1 or t(11;14), who are relapsed or are refractory to chemoimmunotherapy and a covalent irreversible BTKi (Cohort E)
• Participants with MZL (including splenic, nodal, and extra nodal MZL) who are relapsed or refractory to chemoimmunotherapy and a covalent irreversible BTKi (Cohort F)
• Participants with FL who are relapsed or refractory to chemoimmunotherapy, immunomodulatory agents (i.e. lenalidomide plus rituximab) (Cohort G)
• Have measurable disease defined as at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral CT scan
• Has a lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy or bone marrow aspirate (Cohort D) at Screening Part 2 (Cohort H): confirmed diagnosis of WM; participants who are relapsed or refractory to standard therapies for WM including chemoimmunotherapy and a covalent irreversible BTKi
• Has active disease defined as 1 of the following: systemic symptoms, physical findings, laboratory abnormalities, coexisting disease
• Has measurable disease, satisfying any of the following: at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral CT scan (minimum measurement must be >15 mm in the longest diameter or >10 mm in the short axis); IgM ≥450 mg/dL; or bone marrow infiltration of 10%
• Has fresh bone marrow aspirate or a lymph node biopsy for biomarker analysis at Screening or a lymph node biopsy from an archival
Exclusion Criteria:
• Has active HBV/HCV infection (Part 1 and Part 2)
• Has a history of malignancy ≤3 years before providing documented informed consent. Participants with basal cell carcinoma of skin, squamous cell carcinoma of skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potential curative therapy are not excluded. Participants with low-risk, early-stage prostate cancer (T1-T2a, Gleason score ≤6, and prostate-specific antigen <10 ng/mL) either treated with definitive intent or untreated in active surveillance with SD are not excluded
• Has active central nervous system (CNS) disease
• Has an active infection requiring systemic therapy
• Has received prior systemic anti-cancer therapy within 4 weeks prior to allocation
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
• Has any clinically significant gastrointestinal abnormalities that might alter absorption
• History of severe bleeding disorders
Drug: Nemtabrutinib
Hematologic Malignancies, Non-Hodgkins Lymphoma, Waldenstroms Macroglobulinaemia, Chronic Lymphocytic Leukaemia
UT Southwestern
The Pediatric Acute Leukemia (PedAL) Screening Trial - A Study to Test Bone Marrow and Blood in Children With Leukemia That Has Come Back After Treatment or Is Difficult to Treat - A Leukemia & Lymphoma Society and Children's Oncology Group Study
This study aims to use clinical and biological characteristics of acute leukemias to screen for patient eligibility for available pediatric leukemia sub-trials. Testing bone marrow and blood from patients with leukemia that has come back after treatment or is difficult to treat may provide information about the patient's leukemia that is important when deciding how to best treat it, and may help doctors find better ways to diagnose and treat leukemia in children, adolescents, and young adults.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kathleen Ludwig
114894
All
up to 22 Years old
Phase 1/Phase 2
NCT04726241
STU-2022-0170
Inclusion Criteria:
• Patients must be less than 22 years of age at the time of study enrollment
• Patient must have one of the following:
• Patient has known or suspected relapsed/refractory (including primary refractory) AML
• This includes isolated myeloid sarcoma
• Patient has known or suspected relapsed/refractory (including primary refractory) myeloid leukemia of Down syndrome
• Patient has known or suspected relapsed ALL that meets one of the following criteria:
• Second or greater B-ALL medullary relapse, excluding KMT2Ar.
• Any first or greater B-ALL medullary relapse involving KMT2Ar.
• Any first or greater T-ALL medullary relapse with or without KMT2Ar.
• Patient has known or suspected relapsed/refractory (including primary refractory) mixed phenotype acute leukemia (MPAL)
• Patient has known or suspected de novo or relapsed/refractory (including primary refractory) treatment-related AML (t-AML) or treatment-related myelodysplastic syndrome (t-MDS)
• Patient has known or suspected de novo or relapsed/refractory (including primary refractory) myelodysplastic syndrome (MDS)
• Patient has known or suspected de novo or relapsed/refractory (including primary refractory) juvenile myelomonocytic leukemia (JMML)
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Procedure: Biospecimen Collection
Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome, Juvenile Myelomonocytic Leukemia, Acute Myeloid Leukemia, Myeloid Leukemia Associated With Down Syndrome, Mixed Phenotype Acute Leukemia, Leukemia, Other, Myeloid and Monocytic Leukemia, Acute Myeloid Leukemia Post Cytotoxic Therapy, Myelodysplastic Syndrome Post Cytotoxic Therapy
Children’s Health
POCUS: Hemostatic Potential and Joint Health in Patients With Severe Hemophilia A on Novel Replacement Therapies
This is a prospective, randomized control trial in which each patient will be randomly assigned to receive either extended half-life factor VIII based replacement therapy or non-FVIII based replacement therapy, which are both standard of care treatment for persons with Hemophilia A.
Call 214-648-5005
studyfinder@utsouthwestern.edu, susan.corley@childrens.com
Jessica Garcia
181672
All
up to 17 Years old
Phase 4
NCT04690322
STU-2020-1378
Inclusion Criteria:
• Subjects with moderate hemophilia A (baseline factor VIII activity 1-5%) or severe hemophilia A (baseline factor VIII activity <1%) on prophylactic standard half-life FVIII infusions OR subjects with moderate or severe hemophilia A who have not started prophylactic treatment
• Less than 18 years of age
Exclusion Criteria:
• Subjects with documented FVIII inhibitor
• Subjects with a history of ≥ 2 target joints
• Subjects with a history of synovectomy
• Currently using medications known to impact bone and mineral metabolism (e.g., bisphosphonates, corticosteroids, estrogen, testosterone, calcitonin, thyroid hormone therapy);
• Disease states known to affect bone integrity (e.g., primary hyperparathyroidism, Paget's disease, clinically significant liver disease)
Drug: Eloctate, Drug: Adynovate, Drug: Emicizumab
Hemophilia A, Bones and Joints, Other Hematopoietic, Factor VIII
Children’s Health
'Re-Priming' RT After Incomplete Response to CAR-T in R/R NHL
This is a single-arm open-label phase I/II trial studying the safety and efficacy of focal 're-priming' radiation therapy (RT) to FDG-avid residual sites of disease in relapsed/refractory non-Hodgkin lymphoma (R/R NHL) patients with incomplete response (IR) to CAR T-cell therapy (CAR-T) by day 30 post-CAR-T PET/CT. We hypothesize that focal 're-priming' RT will be safe (phase I) and improve conversion to metabolic complete response (CR) by day 90 post-CAR-T PET/CT from 29% (historical control) to 58% (phase II).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kiran Kumar
181795
All
18 Years and over
Phase 1/Phase 2
NCT04601831
STU-2020-1106
Inclusion Criteria:
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at screening
• Biopsy-proven histological high-grade non-Hodgkin lymphoma, such as diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma.
• Prior treatment with any CD19-directed CAR T-cell therapy, such as tisagenlecleucel (tisa-cel, Kymriah), axicabtagene ciloleucel (axi-cel, Yescarta), or lisocabtagene maraleucel (liso-cel).
• Incomplete response noted on day 30 PET post-CAR-T, defined as not achieving CR per Lugano 2014 classification
• Ability to understand and the willingness to sign a written informed consent
• All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• 1 A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
Exclusion Criteria:
• Prior "definitive" radiation therapy (40-50 Gy EQD2 with an α/β of 10) to one or more sites of incomplete response as noted on day 30 post-CAR-T PET/CT scan within the past one year. Prior "palliative" radiation therapy (<40 Gy EQD2) permissible at discretion of treating physician.
• Intracranial site of incomplete response as noted on day 30 post-CAR-T PET/CT scan or any active central nervous system involvement by malignancy.
• Active grade 3 or higher CRS or neurotoxicity related to CAR-T.
• Patients with prior history of auto-immune disease or other contraindication to RT.
• Patients with life expectancy < 3 months.
• Psychiatric illness/social situations that would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
Radiation: Focal radiation therapy (RT)
Non-hodgkin Lymphoma, Non-Hodgkins Lymphoma
CAR-T, Radiation therapy, NHL, DLBCL, RT
UT Southwestern
FUVID Study: Functional Characterization of Children With Chronic Venous Thromboembolic Disease
This is a multi-center prospective cohort study of patients with first-episode deep venous thrombosis and pulmonary embolism.
Call 214-648-5005
studyfinder@utsouthwestern.edu, kendra.malone@childrens.com, FUVID@utsouthwestern.edu
Ayesha Zia
149180
All
8 Years to 21 Years old
NCT04583878
STU-2020-0868
Inclusion Criteria:
• Ages 8 to ≤ 21 years
• Participant must be able to speak and understand English
• Be willing to participate and able to comply with the study protocol
• For participants with PE: Children with acute, radiologically confirmed pulmonary embolism (PE) with our without DVT
• For control group: Cohort 1: Children who are prescribed physical activity restrictions for 2 up to 12 weeks following any minor outpatient surgery or, minor injury (surgery or injury is referred to as "diagnosis" hereafter) Cohort 2: Children who are not prescribed physical activity restrictions and are otherwise considered to be healthy.
Exclusion Criteria:
• Congenital heart disease with abnormal pulmonary circulation or with in-situ pulmonary artery thrombosis
• Chronic kidney disease
• Chronic inflammatory or an autoimmune disorder (such as systemic lupus erythematosus, juvenile rheumatoid disorder, inflammatory bowel disease, and sickle cell disease)
• A metabolic or endocrinological disorder such as diabetes mellitus or thyroid disorder
• History of or active cancer
• Pregnant
• Musculoskeletal limitations to exercise expected to be present uptil 4 months post-diagnosis
• Weight ≥ 300 lbs
• Contraindications to magnetic resonance imaging
• Frequent severe exacerbations of asthma defined by two or more bursts of systemic glucocorticoids (more than three days each) in the previous year or at least one hospitalization, intensive care unit stay or mechanical ventilation in the previous year. Patients should also be excluded if there are daily symptoms of asthma requiring daily use of short-acting bronchodilators such as albuterol or levalbuterol administration. The use of controller medications such as daily inhaled corticosteroids for mild persistent asthma is not exclusionary.
• Has any other medical condition, which in the opinion of the investigator may potentially compromise the safety or compliance of the patient or may preclude the patient's successful completion of the clinical study Additional exclusion criteria for participants with PE:
• Prior history of DVT or PE (upper extremity, cerebral sinus venous thrombosis and abdominal thromboses encountered as a neonate are not exclusion criteria)
• Lack of anticoagulant treatment for the acute VTE due to contraindications
Diagnostic Test: Blood draw (Visit 1), Diagnostic Test: Blood draw (Visits 2 and 3)
Pulmonary Embolism, Deep Venous Thrombosis, Cardiovascular, Lung/Thoracic
UT Southwestern; Children’s Health; Parkland Health & Hospital System
Use Of A Response-Adapted Ruxolitinib-Containing Regimen For The Treatment Of Hemophagocytic Lymphohistiocytosis
This study is a multi-site Phase Ib/II, 2-arm non-randomized clinical trial to determine the efficacy and tolerability of a response-adapted regimen combining ruxolitinib, dexamethasone, and etoposide as Frontline therapy for patients with newly diagnosed hemophagocytic lymphohistiocytosis (HLH) or as Salvage therapy for patients with relapsed/refractory HLH. Primary Objective - To determine the efficacy and tolerability of a response-adapted ruxolitinib-containing regimen for patients with newly diagnosed HLH. Secondary Objectives - To describe the efficacy and tolerability of a response-adapted ruxolitinib-containing regimen for patients with relapsed/refractory HLH. - To describe the overall response and outcome for patients with newly diagnosed or relapsed/refractory HLH who are treated with this response-adapted ruxolitinib-containing regimen. Exploratory Objectives - To estimate the pharmacokinetic (PK) parameters of ruxolitinib, assess covariates of ruxolitinib pharmacokinetics, and test whether the drug's effectiveness is correlated with systemic drug exposure. - To query specific immunologic biomarkers and determine whether the levels of these biomarkers correlate with disease response and outcome.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Jessica.Quicano@childrens.com
Erin Butler
104034
All
6 Weeks to 22 Years old
Phase 1/Phase 2
NCT04551131
STU-2023-0217
Inclusion Criteria:
Frontline Arm:
• Patient is ≥6 weeks and ≤22 years of age.
• Patient weighs ≥3 kg.
• Patient is able to take medication PO and/or patient or parent is willing to have NG tube placed if patient is unable to take medications PO.
• Patient has active HLH if:
• Patient has ≥5 of 8 Diagnostic HLH criteria listed below, OR
• Patient has known fHLH (e.g., patient has pathogenic/likely pathogenic germline variant(s) in genes such as PRF1, UNC13D, STX11, STXBP2, LYST, RAB27A, XIAP, SH2D1A, NLCR4) and meets ≥4 of the diagnostic HLH criteria listed below, OR
• Patient has high likelihood of fHLH based on absent perforin, SAP, XIAP expression and meets ≥4 of the Diagnostic HLH Criteria listed below:
• Fever
• Splenomegaly (If present at any point prior to starting study drug)
• Cytopenias affecting ≥2 of 3 cell lineages in the peripheral blood (hemoglobin <9 g/dL, platelets <100 × 10^9/L, ANC <1000/mm^3)
• Hypertriglyceridemia (fasting triglycerides ≥265 mg/dL) or hypofibrinogenemia (fibrinogen ≤150 mg/dL)
• Presence of hemophagocytosis in BM or other tissues
• Low or absent NK-cell activity (if present at any point prior to starting study drug) OR decreased CD107a mobilization (if present at any point prior to starting study drug)
• Ferritin ≥500 ng/mL
• Soluble IL-2 receptor (CD25) ≥2400 U/mL
• Patient has not received prior HLH therapy, except steroids (any dose or length of therapy is allowed) OR anakinra (any dose or length of therapy is allowed).
• Patient, parent, or legal authorized representative (LAR) must provide informed consent.
Inclusion Criteria:
Salvage Arm:
• Patient is ≥6 weeks and ≤22 years of age.
• Patient weighs ≥3 kg.
• Patient or parent is willing to have the NG tube placed if patient is unable to take medications PO.
• Patient has past history of HLH, defined as meeting ≥5 of 8 HLH- 2004 diagnostic criteria for those with no known HLH-associated mutations, OR ≥4 of 8 HLH-2004 diagnostic criteria for those with known familial disease.
• Patient must have active HLH at the time of eligibility assessment, defined as 3 or more of the following Relapsed/Refractory HLH Criteria:
• Fever
• Splenomegaly (recurrent or worsening)
• ANC <1000/mm^3 × 2 assessments over at least 3 days OR platelets <100 × 10^9/L × 2 assessments over at least 3 days, OR need for platelet transfusions
• Hypofibrinogenemia (fibrinogen ≤150 mg/dL)
• Soluble IL-2 receptor level ≥ 2400 U/mL
• Worsening CNS symptoms OR new abnormal brain magnetic resonance imaging (MRI) findings deemed consistent with CNS HLH by the primary treating physician OR CSF cell count ≥5 mm^3 (with or without hemophagocytosis) OR CSF protein higher than the institutional upper limit of normal OR CSF neopterin higher than the institutional upper limit of normal
• Presence of hemophagocytosis in the BM or other tissues
• Increasing ferritin × 2 assessments over at least 3 days (both levels must be ≥2000 ng/mL)
• Patient must be deemed by the primary treating physician to have not responded to prior therapy by either not having or maintaining a response
• Patient must have received prior HLH-directed therapy:
• At least 2 weeks of steroids (equivalent to at least 5 mg/m^2/day dexamethasone or 1 mg/kg/day methylprednisolone) AND at least 2 doses of etoposide; OR
• At least 1 dose of ATG
• Patient or parent/LAR must provide informed consent. Laboratory findings must be given on at least 2 assessments, each completed at least 1 day apart, EXCEPT CNS radiologic/laboratory findings in which a single abnormal value is sufficient.
Exclusion Criteria:
Frontline and Salvage Arms:
• Patient is <6 weeks or >22 years of age.
• Patient weighs <3 kg.
• Patient has isolated CNS disease.
• Life expectancy is <2 weeks.
• Patient is likely to require <4 weeks of therapy (i.e., HSCT is imminent).
• Patients with creatinine clearance (CrCl) <15 mL/min who are NOT receiving dialysis.
• Patient has evidence of severe organ dysfunction, defined as: Severe liver dysfunction (ALT >1000 U/L), OR Cardiorespiratory failure requiring any ionotropic support OR extracorporeal life support, OR high frequency oscillatory ventilation, other forms of respiratory support or ventilation are allowed if the patient is not on vasopressors)
• Patient with pre-existing rheumatologic disorder.
• Patient with known active malignancy.
• Patient with previous HSCT, except when HSCT was for treatment of HLH.
• Patient is pregnant or lactating.
• Patients who expect to conceive or father children within the projected duration of the study and/or who are unwilling to use highly effective methods of contraception throughout the duration of the study, starting with the screening visit through the end of the treatment visit.
• Patient has suspected or known fungal disease.
• Patient is unable to tolerate administration of drugs PO or NG.
• Patient is taking rifampin or St. John's Wort.
• Patient is taking another investigational agent or is enrolled on another treatment protocol.
• Patient, parent, or LAR are unable or unwilling to provide informed consent. Additional Exclusion Criteria for the Frontline Arm:
• Patient has or is receiving treatment with a JAK inhibitor (including ruxolitinib), ATG, alemtuzumab, etoposide, tocilizumab, emapalumab or any other HLH-directed therapy other than steroids or anakinra (as defined in the Frontline Arm Inclusion Criteria, #5). Additional Exclusion Criteria for the Salvage Arm:
• Patient has or is receiving treatment with a JAK inhibitor (including ruxolitinib) or alemtuzumab within the last 3 months.
• Patient has received therapy on the Frontline Arm of this trial.
Drug: Ruxolitinib, Drug: Dexamethasone, Drug: Etoposide
Hemophagocytic Lymphohistiocytosis, Other Hematopoietic
Hemophagocytic lymphohistiocytosis, Newly Diagnosed, Frontline therapy, Refractory, Relapsed, Response-adapted, Salvage therapy
Children’s Health
Noninvasive Detection and Assessment of Therapy Response in Multiple Myeloma Using Whole-Body MRI
This study is designed to prospectively determine the sensitivity, specificity, and diagnostic accuracy of whole-body MRI (WBMRI) with Dual-Echo T2-weighted acquisition for Enhanced Conspicuity of Tumors (DETECT) for the detection of multiple myeloma. Subjects will undergo WBMRI and fluorodeoxyglucose (FDG) positron emission tomography (PET) for research purposes either at one time point for cross-sectional study or at four time points for longitudinal study: baseline, prior to bone marrow transplant (BMT), prior to maintenance therapy, and post BMT. The results of these imaging procedures will be compared to standard of care whole body x-ray and bone marrow biopsy results.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Avneesh Chhabra
139376
All
18 Years and over
N/A
NCT04493411
STU-2019-0834
Inclusion Criteria:
• Patients with pathologically confirmed myeloma.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1, or 2.
• For cross-sectional study, no additional required treatment schedule. For longitudinal study: Patients scheduled to undergo bone marrow biopsy (BMB) and induction therapy (or have gone through 1-2 cycles of induction therapy), followed by either bone marrow transplantation (BMT) or consolidation therapy.
• Women of child-bearing potential must agree to undergo a urine pregnancy screening to prevent imaging of pregnant patients. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: 1) Has not undergone a hysterectomy or bilateral oophorectomy; or 2) Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
• Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing; since pregnancy is a contraindication to administration of gadolinium-based contrast agents. Furthermore, there is a potential for congenital abnormalities and the potential to harm nursing infants, associated with FDG-PET.
• Any contraindication to MRI per Radiology Department's routine protocol, e.g. MRI-incompatible objects, including but not limited to medical devices and other foreign bodies.
• Known severe allergic reaction to Gadolinium-based contrast agents.
• Patients with uncontrollable claustrophobia, severe lower back pain, and uncontrollable tremors, to the point that it would render them unable to tolerate an MRI study.
Procedure: WBMRI, Procedure: Positron Emission Tomography/Computed Tomography (PET/CT)
Multiple Myeloma
magnetic resonance imaging, positron emission tomography
UT Southwestern
The OPAL Study: AVM0703 for Treatment of Lymphoid Malignancies (OPAL)
This is an open-label, Phase 1/2 study designed to characterize the safety, tolerability, Pharmacokinetics(PK), and preliminary antitumor activity of AVM0703 administered as a single intravenous (IV) infusion to patients with lymphoid malignancies.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
67555
All
12 Years to 95 Years old
Phase 1/Phase 2
NCT04329728
STU-2021-0058
Inclusion Criteria:
• 1. Age ≥12 years and weight ≥40 kg;
• Histologically confirmed diagnosis per 2016 World Health Organization (WHO) classification of lymphoid neoplasms160 and per the 2016 WHO classification of acute leukemia161 of the following indications:
• DLBCL, including arising from follicular lymphoma;
• High-grade B-cell lymphoma;
• MCL;
• Primary mediastinal large B-cell lymphoma;
• Primary DLBCL of the CNS;
• Burkitt or Burkitt-like lymphoma/leukemia;
• CLL/SLL; or
• B-lymphoblastic leukemia/lymphoma, T-lymphoblastic leukemia/lymphoma, acute leukemia/lymphoma, acute leukemias of ambiguous lineage, or NK cell lymphoblastic leukemia/lymphoma;
• Patients must have relapsed or refractory (R/R) disease with prior therapies defined below:
• DLBCL and high-grade B-cell lymphoma: e) R/R after autologous hematopoietic cell transplant (HCT); or f) R/R after chimeric antigen receptor T-cell (CAR T) therapy; or g) Patients not eligible for autologous HCT or CAR T therapy; or h) R/R after ≥2 lines of therapy including anti-CD20 antibody and failed, intolerant or ineligible for polatuzamab vedotin, or for whom no standard therapy is available.
• MCL: c) R/R after autologous HCT; or d) Patients not eligible for autologous HCT must have failed acalabrutinib or be R/R after ≥2 lines of therapy including at least 1 of the following: a Bruton's tyrosine kinase (BTK) inhibitor, bortezomib, or lenalidomide; or for whom no standard therapy is available;
• Primary mediastinal large B-cell lymphoma: R/R after ≥1 line of therapy and are not eligible for or have recurred after autologous HCT or CAR T cell therapy, or for whom no standard therapy is available;
• Primary DLBCL of the CNS: R/R after ≥1 line of therapy including methotrexate (unless intolerant to methotrexate) and are not eligible for or have recurred after autologous HCT or CAR T cell therapy, or for whom no standard therapy is available;
• Burkitt or Burkitt-like lymphoma/leukemia: R/R after ≥1 line of therapy including methotrexate (unless intolerant to methotrexate) and are not eligible for or have recurred after autologous HCT or CAR T cell therapy, or for whom no standard therapy is available;
• CLL/SLL: patients who have active disease requiring treatment and who are deemed at high-risk for disease progression by the investigator or have high risk features per the iwCLL criteria, such as primary resistance to first-line chemo(immune)therapy, or progression of disease <3 years after fludarabine-based chemo(immune)therapy, or leukemia cells with del(17p)/TP53 mutation, must be: d) R/R after autologous or allogeneic HCT; or e) Patients not eligible for HCT; or f) R/R after ≥2 lines of therapy including at least 1 of the following: a BTK inhibitor, venetoclax, idelalisib, or duvelisib, or for whom no standard therapy is available;
• Acute lymphoblastic leukemia (ALL): c) R/R after allogeneic HCT and for whom no standard therapy is available; or d) Patients not eligible for allogeneic HCT must be R/R according to the following disease specific specifications:
• B-cell lymphoblastic leukemia/lymphoma: ≥2 lines of therapy including approved CAR T cell therapies, inotuzumab ozogamicin, or blinatumomab, or for whom no standard therapy is available;
• T-cell lymphoblastic leukemia/lymphoma: ≥2 lines of therapy including nelarabine, or for whom no standard therapy is available;
• NK cell leukemia/lymphoma: ≥1 line of therapy or for whom no standard therapy is available;
• All other diagnoses: R/R after autologous or allogeneic HCT; or R/R after at least one line of therapy, or for whom no standard therapy is available.
• Lansky (12 to 15 years of age) (Appendix G) or Karnofsky (≥16 years of age) (Appendix H) performance status ≥50;
• Screening laboratory values that meet all of the following criteria:
• Absolute neutrophil count ≥0.05 × 109/L;
• Platelet count ≥25 × 109/L;
• Hemoglobin ≥6.5 g/dL;
• • Aspartate aminotransferase or alanine aminotransferase ≥2.5 × ULN, unless due to the disease;
• Total bilirubin <1.5 × ULN (if secondary to Gilbert's syndrome, <3 × ULN is permitted), unless due to the disease; and
• Glomerular filtration rate ≥30 mL/min ; except for patients on metformin at baseline GFR must be ≥45 mL/min; GFR can be calculated by the Cockcroft-Gault formula Appendix C);
• Minimum level of pulmonary reserve defined as
• The ability to understand and willingness to sign a written informed consent form (ICF) and the ability to adhere to the study schedule and prohibitions. Patients under the age of 18 years (or other age as defined by regional law or regulation) must be willing and able to provide written assent and have a parent(s) or guardian(s) willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to performance of any study-related procedure.
Exclusion Criteria:
• Patients who meet any of the following criteria will be excluded from participation in the study for Phase 2:
• History of another malignancy, except for the following:
• Adequately treated local basal cell or squamous cell carcinoma of the skin;
• Adequately treated carcinoma in situ without evidence of disease;
• Adequately treated papillary, noninvasive bladder cancer; or
• Other cancer that has been in complete remission for ≥2 years. Patients with low-grade prostate cancer, on active surveillance, and not expected to clinically progress over 2 years are allowed;
• Significant cardiovascular disease (e.g., myocardial infarction, arterial thromboembolism, cerebrovascular thromboembolism) within 3 months prior to the start of AVM0703 administration, angina requiring therapy, symptomatic peripheral vascular disease, New York Heart Association Class III or IV congestive heart failure, left ventricular ejection fraction <30%, left ventricular fractional shortening <20%, or uncontrolled ≥Grade 3 hypertension (diastolic blood pressure >100 mmHg or systolic blood pressure >150 mmHg) despite antihypertensive therapy for patients ≥18 years of age, or uncontrolled stage 2 hypertension (diastolic blood pressure >90 mmHg or systolic blood pressure >140 mmHg) despite antihypertensive therapy for patients ≥12 years of age;
• Significant screening electrocardiogram (ECG) abnormalities, including unstable cardiac arrhythmia requiring medication, atrial fibrillation/flutter, second degree atrioventricular (AV) block type 2, third-degree AV block, ≥Grade 2 bradycardia, or heart rate corrected QT interval using Fridericia's formula >480 msec;
• Known gastric or duodenal ulcer;
• Uncontrolled type 1 or type 2 diabetes;
• Known hypersensitivity or allergy to the study drug or any of its excipients;
• Untreated ongoing bacterial, fungal, or viral infection (including upper respiratory tract infections) at the start of AVM0703 administration, including the following:
• Positive hepatitis B surface antigen and/or hepatitis B core antibody test plus a positive hepatitis B polymerase chain reaction (PCR) assay. Patients with a negative PCR assay are permitted with appropriate antiviral prophylaxis;
• Positive hepatitis C virus antibody (HCV Ab) test. Patients with a positive HCV Ab test are eligible if they are negative for hepatitis C virus by PCR;
• Positive human immunodeficiency virus (HIV) antibody test with detectable HIV load by PCR, or the patient is not able to tolerate antiretroviral therapy; or
• Positive tuberculosis test during screening; test must be positive and not indeterminate due to anergy; if the result is indeterminate due to anergy the patient must not have a history of recent exposure to tuberculosis. Patients in Phase 2 repeat dosing cohorts should not travel to any destination where they might be exposed to tuberculosis during their entire treatment period with AVM0703.
• Received live vaccination within 8 weeks of screening;
• Pregnant or breastfeeding;
• Concurrent participation in another therapeutic clinical study (except AVM0703-001); or
• Uncontrolled bipolar disorder or schizophrenia. Patients with a diagnosis, past or current, of bipolar disorder or schizophrenia or having a history of severe depression or substance abuse must be prophylactically treated with circadian physiologic hydrocortisone per section 5.5.3.3 CNS prophylaxis, without exception.
Drug: AVM0703
Lymphoma, Lymphoid Leukemia, Lymphoid Malignancies
Diffuse large B-cell lymphoma (DLBCL), B-cell lymphoma, Mantle cell lymphoma (MCL), Primary mediastinal large B-cell Lymphoma, Primary DLBCL of the central nervous system (CNS), Burkitt or Burkitt-like lymphoma/leukemia, Chronic lymphocytic leukemia (CLL), Small lymphocytic leukemia (SLL), B-cell leukemia/lymphoma, T-cell leukemia/lymphoma, Acute leukemias of ambiguous lineage, Natural Killer (NK) cell lymphoblastic leukemia/lymphoma, Advanced or Aggressive lymphoma/lymphoproliferative disease, Follicular Lymphoma
Children’s Health
Safety, Tolerability and Pharmacokinetics of a Monoclonal Antibody Specific to B-and T-Lymphocyte Attenuator (BTLA) as Monotherapy and in Combination With an Anti-PD1 Monoclonal Antibody for Injection in Subjects With Advanced Malignancies
The primary objective is to assess the safety and tolerability of TAB004 as monotherapy and in combination with toripalimab in subjects with selected advanced solid malignancies, including lymphoma, and to evaluate the recommended Phase 2 dose. The secondary objectives are to: 1) describe the pharmacokinetic (PK) profile of TAB004 monotherapy and in combination with toripalimab and to describe the PK profile of toripalimab when administered with TAB004, 2) evaluate antitumor activity of TAB004 monotherapy and in combination with toripalimab; and 3) determine the immunogenicity of TAB004 monotherapy and in combination with toripalimab and to determine the immunogenicity of toripalimab when administered with TAB004. The exploratory objectives are to: 1) evaluate pharmacodynamic effects of TAB004 on its target receptor BTLA, as well as effects on the immune system; 2) evaluate biomarkers that may correlate with activity of TAB004 as monotherapy and in combination with toripalimab; 3) evaluate the utility of BTLA ligand, herpesvirus-entry mediator (HVEM), and additional exploratory biomarkers that could aid in selection of appropriate subjects for TAB004 monotherapy and in combination with toripalimab.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Farrukh Awan
180091
All
18 Years and over
Phase 1
NCT04137900
STU-2020-0419
Inclusion Criteria:
• 1. Able to understand and willing to sign the Informed Consent Form;
• 2. Male or female ≥ 18 years;
• 3. Subjects with histologically or cytologically confirmed advanced unresectable or metastatic solid tumor, including lymphoma that have progressed following prior treatment. In Part A, subjects must have received, or be ineligible for or intolerant of all available approved or standard therapies known to confer clinical benefit including immunotherapy, or for whom no standard therapy exists; in Part B, subjects with advanced or metastatic solid tumors, including but not limited to lymphoma, melanoma, NSCLC, or other tumors with agreement of the Sponsor, who must have received at least one line of therapy for advanced or metastatic disease, but are not required to have received all standard therapies known to confer clinical benefit; In Part C, subjects must have received at least one line of therapy for advanced or metastatic disease but are not required to have received all standard therapies known to confer clinical benefit; In Part D, subjects with advanced or metastatic solid tumors that may include but not limited to lymphoma, melanoma, NSCLC, RCC or UC who must have received at least one line of therapy for advanced or metastatic disease, but are not required to have received all standard therapies known to confer clinical benefit.
• 4. Measurable disease per RECISTv1.1 and iRECIST, or RECIL 2017 for lymphoma
• 5. ECOG performance status of 0 or 1 with life expectancy of 3 months in the opinion of the investigator.
• 6. Adequate organ and marrow function, as defined below:
• Hemoglobin 8.0 g/dL within first 2 weeks prior to first dose of TAB004 (are not requiring a transfusion within 14 days prior to dosing)
• Absolute neutrophil count (ANC) 1.0 x 109 /L (1,000 /mm3)
• Absolute lymphocyte count ≥ 0.6 x 109/L (600/mm3)
• Platelet count 75 x 109 /L (75,000 /mm3), and not requiring platelet transfusions within the 5 days prior to dosing
• Total bilirubin ≤ 1.5 x ULN except subjects with documented Gilbert's syndrome who must have a baseline total bilirubin ≤ 3.0 mg/dL
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN; for subjects with hepatic metastases, ALT and AST ≤ 5 x ULN
• Serum creatinine ≤ 1.5 x ULN OR calculated creatinine clearance (CrCl) or 24 hour urine CrCl ≥ 40 mL/minute Cockcroft-Gault formula will be used to calculate CrCl. 24-hour urine CrCl will be derived using the measured creatinine clearance formula
• International normalized ratio (INR) ≤ 2.0 and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN; applies only to subjects who do not receive therapeutic anticoagulation; subjects receiving therapeutic anticoagulation (such as low-molecular weight heparin or warfarin) should be on a stable dose
• 7. Willingness to provide consent for biopsy samples (In Part A, fresh pre-treatment biopsies will be requested from subjects with safely accessible lesions. For subjects who cannot provide a fresh pre-treatment biopsy, request for the most recent accessible archival specimen will be required. In Part B, C and D, fresh pre-treatment biopsies will be required from subjects with safely accessible lesions. The most recent archival specimens will also be requested).
• 8. Females of childbearing potential who are sexually active with a nonsterilized male partner must use effective contraception from time of screening, and must agree to continue using such precautions for 90 days after the final dose of TAB004 or toripalimab; cessation of birth control after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control.
• 9. Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as at least 12 months with no menses confirmed by follicle-stimulating hormone [FSH] levels. FSH testing will be conducted at the Screening visit to confirm post-menopausal status).
• 10. Subjects must use effective contraception. Nonsterilized males who are sexually active with a female partner of childbearing potential must use effective contraception from Day 1 and for 90 days after receipt of the final dose of TAB004 or toripalimab.
Exclusion Criteria:
• 1. Concurrent enrollment in another clinical study, unless it is an observational (non interventional) clinical study or the follow-up period of an interventional study.
• 2. Any concurrent anti-cancer therapy, such as but not limited to chemotherapy, targeted therapy, radiotherapy, immunotherapy, or biologic therapy. Radiation treatment for palliative intent is allowed provided that lesions other than those receiving radiation are available to measure response. Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for type 2 diabetes and hormone replacement therapy) is acceptable. Note: Local treatment of isolated lesions for palliative intent is acceptable (e.g., by local surgery or radiotherapy).
• 3. Receipt of any investigational anticancer therapy within 28 days prior to the first dose of TAB004 or, provided documentable, 5 half lives whichever is shorter, except for lymphoma in which the exclusionary period is 2 weeks for immune checkpoint inhibitors only.
• 4. Current or prior use of immunosuppressive medication within 2 weeks prior to the first dose of TAB004, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids not to exceed 10 mg/day of prednisone or equivalent.
• 5. Prior exposure to anti-BTLA, or anti-HVEM antibodies for subjects enrolled into Part A and B only; prior treatment with anti-PD-1 or anti-PDL-1is allowed,including toripalimab for all subjects.
• 6. Prior allogeneic bone marrow transplantation or prior solid organ transplantation.
• 7. Subjects with another malignancy, or history or other malignancy within 3 years that is not expected to relapse. Subjects with non-melanomatous skin cancer or cervical cancer that has been curatively surgically resected are eligible.
• 8. Major surgery (as defined by the investigator) within 28 days prior to first dose of TAB004 or has not recovered to at least Grade 1 from adverse effects from such procedure, or anticipation of the need for major surgery during study treatment.
• 9. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to baseline or to NCI-CTCAE v5.0 Grade 0 or 1, or to levels dictated in the inclusion/exclusion criteria with the exception of neuropathies that are stable or improving and alopecia. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by TAB004 may be included (e.g., hearing loss) after consultation with the medical monitor.
• 10. Active or prior documented autoimmune disease, such as but not limited to systemic lupus erythematosus, multiple sclerosis, inflammatory bowel diseases, rheumatoid arthritis, autoimmune hepatitis, systemic sclerosis, autoimmune vasculitis, autoimmune neuropathies or type 1 insulin-dependent diabetes mellitus. Note: Subjects with the following are not excluded: vitiligo; alopecia; Grave's disease not requiring systemic treatment other than thyroid hormone replacement (within the past 2 years) psoriasis not requiring systemic treatment; controlled celiac disease; subjects with a history of autoimmune hypothyroidism requiring only thyroid hormone replacement therapy; And type 2 diabetes, provided that it is adequately controlled.
• 11. Clinically significant (intracranial, gastrointestinal) bleeding within 2 weeks prior to screening.
• 12. Known history of tuberculosis.
• 13. Subjects with history of or current drug-induced interstitial lung disease or pneumonitis ≥ Grade 2.
• 14. Subjects who have discontinued prior immune therapy due to immune mediated adverse reaction(s).
• 15. Subjects who are known to be human immunodeficiency virus positive.
• 16. Subjects with evidence of hepatitis B or C virus infection, unless their hepatitis is considered to have been cured. (Note that subjects with prior hepatitis B virus infection must have HBV viral load < 100 IU/mL before study enrollment, and must be treated according to local standards; hepatitis C virus infection must have, before study enrollment, no detectable viral load and must be treated according to local standards).
• 17. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis). Infection-related bowel inflammation, such as Clostridium difficile colitis, is not excluded provided that it has been fully resolved for ≥ 6 weeks.
• 18. History of anaphylaxis, or eczema that cannot be controlled with topical corticosteroids asthma.
• 19. Adult asthma that is moderate or severe, or asthma that has required: hospitalization in the last 2 years; invasive mechanical ventilation ever; systemic corticosteroids in the past year for exacerbations; or more than two short acting beta agonist (e.g., albuterol) administrations per month for breakthrough asthma symptoms. A history of childhood asthma or the presence of mild adult asthma that at baseline has symptoms that can be controlled well with inhaled corticosteroids or short acting beta agonists will not be excluded.
• 20. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure according to New York Heart Association Functional Classification ≥ 3, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring adverse events from TAB004, or compromise the ability of the subject to give written informed consent.
• 21. Untreated central nervous system and leptomeningeal metastases or requiring ongoing treatment for these metastases, including corticosteroids. Subjects with previously treated brain metastases may participate provided they are clinically stable for at least 28 days prior to study entry, have no evidence of new or enlarging metastases, and are off steroids.
• 22. Receipt of live attenuated vaccination within 28 days prior to study entry or within 30 days of receiving TAB004.
• 23. Any condition or treatment or diagnostic test that, in the opinion of the investigator or sponsor, would interfere with evaluation of TAB004 or interpretation of subject safety or study results.
• 24. Pregnancy or breast feeding women.
Drug: TAB004, Drug: Toripalimab
Lymphoma, Lung/Thoracic, Melanoma, skin, Hodgkins Lymphoma, Lymphoid Leukemia, Non-Hodgkins Lymphoma, Advanced Unresectable Solid Tumor, Metastatic Solid Tumor
immunotherapy, BTLA, HVEM, check point inhibitor, solid tumor, non-small cell lung cancer, NSCLC, melanoma, lymphoma, monoclonal antibody, phase 1 trial
UT Southwestern
A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations
Phase 1 will evaluate the safety and tolerability at different dose levels of repotrectinib in pediatric and young adult subjects with advanced or metastatic malignancies harboring anaplastic lymphoma kinase (ALK), receptor tyrosine kinase encoded by the gene ROS1 (ROS1), or neurotrophic receptor kinase genes encoding TRK kinase family (NTRK1-3) alterations to estimate the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) and select the Pediatric Recommended Phase 2 Dose (RP2D). Phase 2 will determine the anti-tumor activity of repotrectinib in pediatric and young adult subjects with advanced or metastatic malignancies harboring ROS1 or NTRK1-3 alterations.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tanya Watt
128737
All
up to 25 Years old
Phase 1/Phase 2
NCT04094610
STU-2019-1268
Key
• Documented genetic ROS1 point mutation, fusion, or amplification or NTRK1-3 fusion as identified by local testing in a Clinical Laboratory Improvement Amendments (CLIA) laboratory in the US or equivalently accredited diagnostic lab outside the United States (US) is required.
• Phase 1: Age <12 years; Phase 2: Age 12- 25 years
• Prior cytotoxic chemotherapy is allowed.
• Prior immunotherapy is allowed.
• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
• All subjects must have measurable disease by RECIST v1.1 or Response Assessment in Neuro-Oncology (RANO) criteria at time of enrollment.
• Subjects with a primary CNS tumor or CNS metastases must be neurologically stable on a stable or decreasing dose of steroids for at least 7 days prior to enrollment.
• Subjects must have a Lansky (< 16 years) or Karnofsky (≥ 16 years) score of at least
• 9. Life expectancy greater than or equal to 12 weeks, in the investigator's opinion.
• Adequate hematologic, renal and hepatic function. Phase 2
• Cohort Specific
• Cohort 1: Subjects with NTRK fusion gene positive (NTRK+) advanced solid tumors (including primary CNS tumors), that are tropomyosin receptor kinase (TRK) TKI naïve;
• Cohort 2: subjects with NTRK+ advanced solid tumors (including primary CNS tumors), that are TRK TKI pre-treated;
• Cohort 3: subjects with advanced solid tumors with ROS1 gene fusions or other ROS1 aberrations (including amplifications and point mutations) with measurable disease.
• Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment. Key Exclusion Criteria (Phase 1 and Phase 2):
• Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only.
• Major surgery within 14 days (2 weeks) of start of repotrectinib treatment. Central venous access (Broviac, Mediport, etc.) placement does not meet criteria for major surgery.
• Known active infections requiring ongoing treatment (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) > 480 msec obtained from three ECGs, using the screening clinic ECG machine-derived QTc value
• Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval > 250 msec)
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval
• Peripheral neuropathy of CTCAE ≥grade 2.
• Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.
• Any potential allergies to repotrectinib and/or its excipients.
Inclusion Criteria:
• Documented genetic ROS1 point mutation, fusion, or amplification or NTRK1-3 fusion as identified by local testing in a Clinical Laboratory Improvement Amendments (CLIA) laboratory in the US or equivalently accredited diagnostic lab outside the United States (US) is required.
• Phase 1: Age <12 years; Phase 2: Age 12- 25 years
• Prior cytotoxic chemotherapy is allowed.
• Prior immunotherapy is allowed.
• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
• All subjects must have measurable disease by RECIST v1.1 or Response Assessment in Neuro-Oncology (RANO) criteria at time of enrollment.
• Subjects with a primary CNS tumor or CNS metastases must be neurologically stable on a stable or decreasing dose of steroids for at least 7 days prior to enrollment.
• Subjects must have a Lansky (< 16 years) or Karnofsky (≥ 16 years) score of at least
• 9. Life expectancy greater than or equal to 12 weeks, in the investigator's opinion.
• Adequate hematologic, renal and hepatic function. Phase 2
Inclusion Criteria:
• Cohort Specific
Inclusion Criteria:
• Cohort 1: Subjects with NTRK fusion gene positive (NTRK+) advanced solid tumors (including primary CNS tumors), that are tropomyosin receptor kinase (TRK) TKI naïve;
• Cohort 2: subjects with NTRK+ advanced solid tumors (including primary CNS tumors), that are TRK TKI pre-treated;
• Cohort 3: subjects with advanced solid tumors with ROS1 gene fusions or other ROS1 aberrations (including amplifications and point mutations) with measurable disease.
• Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment. Key Exclusion Criteria (Phase 1 and Phase 2):
• Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only.
• Major surgery within 14 days (2 weeks) of start of repotrectinib treatment. Central venous access (Broviac, Mediport, etc.) placement does not meet criteria for major surgery.
• Known active infections requiring ongoing treatment (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) > 480 msec obtained from three ECGs, using the screening clinic ECG machine-derived QTc value
• Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval > 250 msec)
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval
• Peripheral neuropathy of CTCAE ≥grade 2.
• Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.
• Any potential allergies to repotrectinib and/or its excipients.
Drug: Oral repotrectinib (TPX-0005)
Lymphoma, Locally Advanced Solid Tumors, Metastatic Solid Tumors, Primary CNS Tumors
ALK, ROS1, NTRK1-3, Primary CNS tumor, anaplastic large cell lymphoma, metastatic solid tumor, advanced solid tumor, sarcoma, infantile fibrosarcoma, glioblastoma, soft tissue schwannoma, solitary fibrous tumor, glioma, inflammatory myofibroblastic tumor, pediatric
Children’s Health
A Clinical Trial of BP1002 in Patients With Advanced Lymphoid Malignancies
This study evaluates the safety, pharmacokinetics, and efficacy of BP1002 (L-Bcl-2) antisense oligonucleotide in patients with advanced lymphoid malignancies. Up to 12 evaluable patients with a diagnosis of relapsed or refractory lymphoid malignancies are expected to participate.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Praveen Ramakrishnan Geethakumari
171719
All
18 Years and over
Phase 1
NCT04072458
STU-2023-0236
Inclusion Criteria:
• Adults ≥18 years of age
• Patient has a life expectancy ≥ 3 month
• Patient has relapsed or refractory disease Relapsed lymphoma: Relapsed lymphoma is disease that has responded to treatment but then returns. Refractory lymphoma: Failure to achieve complete response at the end of therapy or progression within 6 months from completion of therapy
• Included Diseases
• DLBCL, including transformed lymphoma
• Mantle Cell Lymphoma
• PTCL
• CTCL
• CLL/SLL
• Follicular lymphoma
• Marginal zone lymphoma
• Hodgkin lymphoma (both classical and lymphocyte predominant)
• Waldenströms Macroglobulinemia
• Must has failed or is not a candidate for available therapies with reasonable likelihood of clinical benefit, which includes FDA approved products and standard of care regimens
• Therapy means at least three front lines of therapy including Hematopoeitic Stem Cell Transplant (HSCT and/or Chimeric Antigen Receptor (CAR) T cells, when applicable
• Females must be of non-childbearing potential, surgically sterile, postmenopausal, or practice adequate methods of contraception during the study
• Males must agree to use an adequate method of contraception during the study
• Eastern Cooperative Oncology Group (ECOG) Performance score of 0, 1, or 2
• Adequate hepatic and renal functions as defined by:
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 times the upper limit of normal (ULN); and
• Total bilirubin ≤1.5 times ULN; and
• Estimated glomerular filtration rate (eGFR) of at least 50ml/min. These estimations can be calculated using the following methods:
• Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equation
• Cockcroft Gault equation
• Modification of Diet in Renal Disease (MDRD study equation)
• Creatinine clearance estimated by 24-hr urine collection for creatinine clearance
• Recovered from the effects of any prior surgery, radiotherapy, or antineoplastic treatment (with the exception of alopecia), based on Investigator assessment
• Willing and able to provide written informed consent
Exclusion Criteria:
• Active non-hematologic malignancy other than lymphoid malignancies treated with immuno- or chemotherapy within the previous 12 months except active non-melanoma, non-invasive skin cancer will be allowed
• Known, active Central Nervous System (CNS) involvement of disease requiring intrathecal therapy. Note: Patients with a history of CNS disease may be allowed to participate based on at least 1 documented, negative spinal fluid assessment within 28 days prior to Screening
• Patient eligible for high dose chemotherapy and autologous stem cell transplant
• Indolent non-Hodgkin lymphoma (iNHL)
• Patients at high risk of Tumor Lysis Syndrome (TLS) a. Bulky disease i. A unidimensional lesion greater than 10 cm and/or b. Lymphocyte count greater than 25,000 per µL
• Receipt of any anti-cancer therapy within 14 days prior to Cycle 1 Day 1 (C1D1)
• Uncontrolled active, untreated, or progressive infection
• Receipt of any investigational agent or on study treatment within 30 days prior to C1D1
• Females who are pregnant, test positive for pregnancy, or are breast-feeding during the Screening period, or intend to become pregnant or breast-feed during the course of the study or within 30 days after last dose of study drug
• Serious intercurrent medical or psychiatric illness which, in the opinion of the Investigator, would interfere with the ability of the participant to complete the study
• Active hepatitis B infection (based on positive surface antigen [HBsAg]), hepatitis C infection (based on Hepatitis C Virus (HCV) positive antibody [HCV Ab]), or human immunodeficiency virus (HIV-1 or HIV-2, based on positive antibody)
• Presence of concurrent conditions that, in the opinion of the Investigator and/or Medical Monitor, may compromise or interfere with any aspect of study conduct or interpretation of results. This includes, but is not limited to, unstable or uncontrolled angina, New York Heart Association (NYHA) class III or IV congestive heart failure, uncontrolled and sustained hypertension, clinically significant cardiac dysrhythmia or clinically significant baseline EKG abnormality (e.g., QTcF >470 msec)
• Within the past 6 months, has had any of the following: myocardial infarction, unstable angina pectoris, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack
• Uncontrolled seizure disorder
• Unable or unwilling to communicate or cooperate with the Investigator or follow the protocol for any reason.
Drug: L-Bcl-2 antisense oligonucleotide
Hodgkin Lymphoma, Waldenström Macroglobulinemia, Cutaneous T-cell Lymphoma (CTCL), Chronic Lymphocytic Leukemia (CLL), Follicular Lymphoma, Marginal Zone Lymphoma, Mantle Cell Lymphoma, Hodgkins Lymphoma, Lymphoid Leukemia, Small Lymphocytic Lymphoma (SLL), DLBCL, Peripheral T-cell Lymphoma (PTCL)
UT Southwestern
Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy
This phase III trial studies whether inotuzumab ozogamicin added to post-induction chemotherapy for patients with High-Risk B-cell Acute Lymphoblastic Leukemia (B-ALL) improves outcomes. This trial also studies the outcomes of patients with mixed phenotype acute leukemia (MPAL), and B-lymphoblastic lymphoma (B-LLy) when treated with ALL therapy without inotuzumab ozogamicin. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a type of chemotherapy called calicheamicin. Inotuzumab attaches to cancer cells in a targeted way and delivers calicheamicin to kill them. Other drugs used in the chemotherapy regimen, such as cyclophosphamide, cytarabine, dexamethasone, doxorubicin, daunorubicin, methotrexate, leucovorin, mercaptopurine, prednisone, thioguanine, vincristine, and pegaspargase or calaspargase pegol work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial will also study the outcomes of patients with mixed phenotype acute leukemia (MPAL) and disseminated B lymphoblastic lymphoma (B-LLy) when treated with high-risk ALL chemotherapy. The overall goal of this study is to understand if adding inotuzumab ozogamicin to standard of care chemotherapy maintains or improves outcomes in High Risk B-cell Acute Lymphoblastic Leukemia (HR B-ALL). The first part of the study includes the first two phases of therapy: Induction and Consolidation. This part will collect information on the leukemia, as well as the effects of the initial treatment, to classify patients into post-consolidation treatment groups. On the second part of this study, patients with HR B-ALL will receive the remainder of the chemotherapy cycles (interim maintenance I, delayed intensification, interim maintenance II, maintenance), with some patients randomized to receive inotuzumab. The patients that receive inotuzumab will not receive part of delayed intensification. Other aims of this study include investigating whether treating both males and females with the same duration of chemotherapy maintains outcomes for males who have previously been treated for an additional year compared to girls, as well as to evaluate the best ways to help patients adhere to oral chemotherapy regimens. Finally, this study will be the first to track the outcomes of subjects with disseminated B-cell Lymphoblastic Leukemia (B-LLy) or Mixed Phenotype Acute Leukemia (MPAL) when treated with B-ALL chemotherapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
67555
All
1 Year to 25 Years old
Phase 3
NCT03959085
STU-2019-1574
Inclusion Criteria:
• B-ALL and MPAL patients must be enrolled on APEC14B1 and consented to eligibility studies (Part A) prior to treatment and enrollment on AALL1732. Note that central confirmation of MPAL diagnosis must occur within 22 days of enrollment for suspected MPAL patients. If not performed within this time frame, patients will be taken off protocol.
• APEC14B1 is not a requirement for B-LLy patients but for institutional compliance every patient should be offered participation in APEC14B1. B-LLy patients may directly enroll on AALL1732.
• Patients must be > 365 days and < 25 years of age
• White blood cell count (WBC) criteria for patients with B-ALL (within 7 days prior to the start of protocol-directed systemic therapy):
• Age 1-9.99 years: WBC >= 50,000/uL
• Age 10-24.99 years: Any WBC
• Age 1-9.99 years: WBC < 50,000/uL with:
• Testicular leukemia
• CNS leukemia (CNS3)
• Steroid pretreatment.
• White blood cell count (WBC) criteria for patients with MPAL (within 7 days prior to the start of protocol-directed systemic therapy):
• Age 1-24.99 years: any WBC NOTE: Patients enrolled as suspected MPAL but found on central confirmatory testing to have B-ALL must meet the B-ALL criteria above (age, WBC, extramedullary disease, steroid pretreatment) to switch to the B-ALL stratum before the end of induction.
• Patient has newly diagnosed B-ALL or MPAL (by World Health Organization [WHO] 2016 criteria) with >= 25% blasts on a bone marrow (BM) aspirate;
• OR If a BM aspirate is not obtained or is not diagnostic of acute leukemia, the diagnosis can be established by a pathologic diagnosis of acute leukemia on a BM biopsy;
• OR A complete blood count (CBC) documenting the presence of at least 1,000/uL circulating leukemic cells if a bone marrow aspirate or biopsy cannot be performed.
• Patient has newly diagnosed B-LLy Murphy stages III or IV.
• Patient has newly diagnosed B-LLy Murphy stages I or II with steroid pretreatment.
• Note: For B-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to B-ALL. For tissue processed by other means (i.e., paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of B-LLy defined by the submitting institution will be accepted.
• Central nervous system (CNS) status must be determined prior to enrollment based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment and cytoreduction. It is recommended that intrathecal cytarabine be administered at the time of the diagnostic lumbar puncture. This is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture. This is allowed prior to enrollment. Systemic chemotherapy must begin within 72 hours of this intrathecal therapy.
• All patients and/or their parents or legal guardians must sign a written informed consent.
• All institutional, Food and Drug Administration (FDA), and NCI requirements for human studies must be met.
Exclusion Criteria:
• Patients with Down syndrome are not eligible (patients with Down syndrome and B-ALL are eligible for AALL1731, regardless of NCI risk group).
• With the exception of steroid pretreatment and steroid cytoreduction or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for the current diagnosis of B-ALL, MPAL, or B-LLy or for any cancer diagnosed prior to initiation of protocol therapy on AALL1732.
• Patients who have received > 72 hours of hydroxyurea within one week prior to start of systemic protocol therapy.
• Patients with B-ALL or MPAL who do not have sufficient diagnostic bone marrow submitted for APEC14B1 testing and who do not have a peripheral blood sample submitted containing > 1,000/uL circulating leukemia cells.
• Patients with acute undifferentiated leukemia (AUL) are not eligible.
• For Murphy stage III/IV B-LLy patients, or stage I/II patients with steroid pretreatment, the following additional exclusion criteria apply:
• T-lymphoblastic lymphoma.
• Morphologically unclassifiable lymphoma.
• Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma.
• Patients with known Charcot-Marie-Tooth disease.
• Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL, regardless of blast immunophenotype.
• Patients requiring radiation at diagnosis.
• Female patients who are pregnant, since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
• Lactating women who plan to breastfeed their infants while on study and for 2 months after the last dose of inotuzumab ozogamicin.
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of study participation. For those patients randomized to inotuzumab ozogamicin, there is a minimum of 8 months after the last dose of inotuzumab ozogamicin for females and 5 months after the last dose of inotuzumab ozogamicin for males.
Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration, Procedure: Bone Marrow Biopsy, Procedure: Bone Scan, Drug: Calaspargase Pegol, Procedure: Computed Tomography, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin Hydrochloride, Drug: Dexamethasone, Drug: Doxorubicin Hydrochloride, Biological: Inotuzumab Ozogamicin, Drug: Leucovorin Calcium, Procedure: Magnetic Resonance Imaging, Drug: Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Procedure: Positron Emission Tomography, Drug: Prednisolone, Other: Questionnaire Administration, Radiation: Radiation Therapy, Radiation: Radiation Therapy, Drug: Thioguanine, Drug: Vincristine Sulfate
B Acute Lymphoblastic Leukemia, Central Nervous System Leukemia, Testicular Leukemia, Mixed Phenotype Acute Leukemia, B Lymphoblastic Lymphoma, Leukemia, Other
Children’s Health