UTSW - Study Finder

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)

Description:

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.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Heather McArthur

Gender: ALL

Age: 18 Years and over

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT06022029

IRB Number: STU-2023-0921

Show full eligibility criteria

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

Interventions: DRUG: ONM-501, DRUG: Cemiplimab

Conditions: Triple Negative Breast Cancer, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Lymphoma, Non-Hodgkin, Mantle Cell Lymphoma, Bladder Cancer, Uveal Melanoma, Recurrent, Cervix Cancer, Carcinoma In Situ, Head and Neck Squamous Cell Carcinoma, Skin Cancer, Metastatic Cancer, Tumor, Solid, Tumor Recurrence

Keywords: 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

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

A Phase 2 Study of Firi-cel in Patients With Relapsed/Refractory Large B-cell Lymphoma (FIRCE-1)

Description:

This is a prospective, open-label, multi-center clinical study designed to evaluate the safety, tolerability, efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity of firicabtagene autoleucel (firi-cel), a CD22-directed autologous Chimeric Antigen Receptor (CAR) T-cell therapy for the treatment of relapsed or refractory large B-cell lymphoma (LBCL).

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Farrukh Awan

Gender: ALL

Age: 18 Years and over

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05972720

IRB Number: STU-2023-0976

Show full eligibility criteria

Interventions: DRUG: Fludarabine (Conditional therapy), DRUG: Cyclophosphamide Monohydrate (Conditional therapy), DRUG: firi-cel (Experimental drug)

Conditions: Cancer, Relapsed/Refractory Large B-cell Lymphoma (LBCL), Non-Hodgkins Lymphoma

Keywords: Lymphoma, CD-22 Expressing Tumor, Chimeric Antigen Receptor, Adoptive Immunotherapy, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Primary Mediastinal B-cell, Lymphoma, Transformed, Lymphoma, Transformed Non-Hodgkin, Lymphoma, Non-Hodgkin, CAR T, CAR T-cell therapy, Cell Therapy, Cellular Immuno-therapy, CRG-022, CD22, FIRCE-1, firicabtagene autoleucel, firi-cel

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

A Safety and Efficacy Study of HCB101, Fc-fusion Protein Targeting SIRPα-CD47 Pathway, in Solid or Hematological Tumors

Description:

The purpose of this study is to find out whether IV injection of HCB101 is an effective treatment for different types of advanced solid tumors or relapsed and refractory non-Hodgkin lymphoma and what side effects (unwanted effects) may occur in subjects aged 18 years old and above.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Tian Zhang

Gender: All

Age: 18 Years and over

Phase: Phase 1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05892718

IRB Number: STU-2023-1031

Show full eligibility criteria

Inclusion Criteria:

• Able to understand and willing to sign the ICF.
• Male and female subjects of ≥18 years of age.
• Histologically/cytologically confirmed, locally advanced solid tumor: subjects with histologically or cytologically confirmed advanced solid tumors refractory to standard therapy, or for which no standard treatment exists or non-Hodgkin lymphoma, relapsed or refractory to at least 2 prior lines of therapy.
• For subjects with advanced solid tumor - must have at least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at baseline.
• For subjects with non-Hodgkin lymphoma - must have non-Hodgkin lymphoma that is measurable or assessable for response per Lugano Classification (with 2016 refinement).
• Must have ECOG performance status of 0 to 2 at Screening.
• Able to provide tumor tissue samples.
• Have life expectancy of ≥12 weeks.

Exclusion Criteria:

• With known history of hypersensitivity to any components of HCB101.
• Known active or untreated CNS metastases and/or carcinomatous meningitis.
• Have undergone a major surgery or radical radiotherapy or palliative radiotherapy or have used a radioactive drug that is not completed at least 2 weeks prior to the first dose of HCB101.
• Clinically significant cardiovascular condition.
• Any previous treatment-related toxicities which have not recovered to ≤ Grade 1 as evaluated by National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 or baseline, except alopecia and anemia.
• With known inherited or acquired bleeding disorder or bleeding diathesis. .
• Have RBC transfusion within 4 weeks prior to Screening.
• With a previously documented diagnosis of hemolytic anemia or Evans Syndrome in the last 3 months.
• Any investigational or approved systemic cancer therapy.
• Active use of vitamin K antagonist anticoagulant like warfarin. Use of low molecular weight heparin and factor Xa inhibitors will be permitted on case by case basis. There will be no restriction for daily aspirin ≤ 81 mg/QD.
• Have used herbal medication within 14 days prior to the first dose of HCB101.
• Have received any treatment targeting the CD47 or SIRPα pathway.
• Have other malignancies requiring treatment within 2 years prior to the first dose of HCB101.
• Participation in another clinical study with an investigational product administered in the last 14 days prior to receiving the first dose of HCB101.
• An investigational device used within 28 days prior to the first dose of HCB101.
• Positive for hepatitis B, active hepatitis C infections, positive for HIV, or known active or latent tuberculosis.
• Known to have a history of alcoholism or drug abuse.

Interventions: Drug: HCB101

Conditions: Advanced Solid Tumor, Refractory Non-Hodgkin Lymphoma, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Hodgkins Lymphoma, Kaposis sarcoma, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Multiple Myeloma, Non-Hodgkins Lymphoma, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Stomach, Thyroid, Urinary Bladder

Keywords: Immunotherapy, CD47, SIRPα, Solid Tumor, Lymphoma

Sites: UT Southwestern; Parkland Health & Hospital System

I'm interested

Share via email

See this study on ClinicalTrials.gov

A Study of AC676 for the Treatment of Relapsed/Refractory B-Cell Malignancies

Description:

This clinical trial is evaluating a drug called AC676 in participants with Relapsed/Refractory B-cell Malignancies. The main goals of the study are to: * Identify the recommended dose of AC676 that can be given safely to participants * Evaluate the safety profile of AC676 * Evaluate the pharmacokinetics of AC676 * Evaluate the effectiveness of AC676

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Farrukh Awan

Gender: ALL

Age: 18 Years and over

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05780034

IRB Number: STU-2023-0813

Show full eligibility criteria

Interventions: DRUG: AC676

Conditions: Relapsed/Refractory B-cell Malignancies, Non-Hodgkins Lymphoma

Keywords: Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), Mantle Cell Lymphoma (MCL), Follicular Lymphoma (FL), Non-Germinal Center B-cell (Non-GCB) Diffuse Large B-cell Lymphoma (DLBCL), Marginal Zone Lymphoma (MZL, Waldenström Macroglobulinemia (WM), Non-Hodgkin Lymphoma (NHL), Bruton's tyrosine kinase-BTK, BTK Degrader, AC676, AC0676

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

A Study to Compare Standard Therapy to Treat Hodgkin Lymphoma to the Use of Two Drugs, Brentuximab Vedotin and Nivolumab

Description:

This phase III trial compares the effect of adding immunotherapy (brentuximab vedotin and nivolumab) to standard treatment (chemotherapy with or without radiation) to the standard treatment alone in improving survival in patients with stage I and II classical Hodgkin lymphoma. Brentuximab vedotin is in a class of medications called antibody-drug conjugates. It is made of a monoclonal antibody called brentuximab that is linked to a cytotoxic agent called vedotin. Brentuximab attaches to CD30 positive lymphoma cells in a targeted way and delivers vedotin to kill them. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs such as doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, dacarbazine, and procarbazine hydrochloride 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. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. It may also lower the body's immune response. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Adding immunotherapy to the standard treatment of chemotherapy with or without radiation may increase survival and/or fewer short-term or long-term side effects in patients with classical Hodgkin lymphoma compared to the standard treatment alone.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Ksenya Shliakhtsitsava

Gender: ALL

Age: 5 Years to 60 Years old

Phase: PHASE3

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05675410

IRB Number: STU-2023-0552

Show full eligibility criteria

Inclusion Criteria:

* Patients must be 5 to 60 years of age at the time of enrollment * Patients with newly diagnosed untreated histologically confirmed classic Hodgkin lymphoma (cHL) (nodular sclerosis, mixed cellularity, lymphocyte-rich, or lymphocyte-depleted, or not otherwise specified \[NOS\]) with stage I or II disease * Patients must have bidimensionally measurable disease (at least one lesion with longest diameter \>= 1.5 cm) * Patients must have a whole body or limited whole body PET scan performed within 42 days prior to enrollment. PET-CT is strongly preferred. PET-MRI allowed if intravenous contrast enhanced CT is also obtained * Pediatric patients (age 5-17 years) with known or suspected mediastinal disease must have an upright posteroanterior (PA) chest X-ray (CXR) for assessment of bulky mediastinal disease. * Note: Pediatric patients who have received both a CT chest and upright PA CXR may meet the definition of bulk through either modality. * Patients \>= 18 years must have a performance status corresponding to Zubrod scores of 0, 1 or 2 * Patients =\< 17 years of age must have a Lansky performance score of \>= 50 * Pediatric patients (age 5-17 years): A serum creatinine based on age/gender as follows (within 28 days prior to enrollment): * 2 to \< 6 years (age): 0.8 mg/dL (male), 0.8 mg/dL (female) * 6 to \< 10 years (age): 1 mg/dL (male), 1 mg/dL (female) * 10 to \< 13 years (age): 1.2 mg/dL (male), 1.2 mg/dL (female) * 13 to \< 16 years (age): 1.5 mg/dL (male), 1.4 mg/dL (female) * \>= 16 years (age): 1.7 mg/dL (male), 1.4 mg/dL (female) OR a 24 hour urine creatinine clearance \>= 50 mL/min/1.73 m\^2 (within 28 days prior to enrollment) OR a glomerular filtration rate (GFR) \>= 50 mL/min/1.73 m\^2 (within 28 days prior to enrollment). GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard) * Note: Estimated GFR (eGFR) from serum or plasma creatinine, cystatin C or other estimates are not acceptable for determining eligibility * For adult patients (age 18 years or older) (within 28 days prior to enrollment): Creatinine clearance \>= 30 mL/min, as estimated by the Cockcroft and Gault formula or a 24-hour urine collection. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on actual body weight * Total bilirubin =\< 2 x upper limit of normal (ULN) (within 28 days prior to enrollment) * Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome * Aspartate aminotransferase (AST) =\< 3 x ULN (within 28 days prior to enrollment) * Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome * Alanine aminotransferase (ALT) =\< 3 x ULN (within 28 days prior to enrollment) * Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome * Shortening fraction of \>= 27% by echocardiogram (ECHO), multigated acquisition scan (MUGA), or functional cardiac imaging scan (within 28 days prior to enrollment) or ejection fraction of \>= 50% by radionuclide angiogram, ECHO, MUGA, or cardiac imaging scan (within 28 days prior to enrollment) * Diffusion capacity of the lung for carbon monoxide (DLCO) \>= 50% of predicted value as corrected for hemoglobin by pulmonary function test (PFT) (within 28 days prior to enrollment). If unable to obtain PFTs, the criterion is: a pulse oximetry reading of \> 92% on room air * Known human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

Exclusion Criteria:

* Patients with nodular lymphocyte predominant Hodgkin lymphoma * Patients with a history of active interstitial pneumonitis or interstitial lung disease * Patients with a diagnosis of inherited or acquired immunodeficiency that is poorly controlled or requiring active medications, such as primary immunodeficiency syndromes or organ transplant recipients * Patients with any known uncontrolled intercurrent illness that would jeopardize the patient's safety such as infection, autoimmune conditions, cardiac arrhythmias, angina pectoris, and gastrointestinal disorders affecting swallowing and/or absorption of pills * Patients with a condition requiring systemic treatment with either corticosteroids (defined as equivalent to \> 10 mg daily predniSONE for patients \>= 18 years or \> 0.5 mg/kg \[up to 10 mg/day\] for patients \< 18 years) or other immunosuppressive medications within 14 days prior to enrollment * Note: Replacement therapy such as thyroxine, insulin, or physiologic corticosteroid for adrenal or pituitary insufficiency is not considered a form of systemic treatment. Inhaled or topical steroids, and adrenal replacement doses (=\< 10 mg daily for patients \>= 18 years or =\< 0.5 mg/kg \[up to 10 mg/day\] predniSONE equivalents) are permitted in the absence of active autoimmune disease * Note: Steroid use for the control of Hodgkin lymphoma symptoms is allowable, but must be discontinued by cycle 1, day 1 * Short term use of corticosteroids for premedication or treatment of an allergy or hypersensitivity is considered an acceptable use of corticosteroids. * Patients with peripheral neuropathy \> grade 1 at the time of enrollment or patients with known Charcot-Marie-Tooth syndrome * Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen * Administration of prior chemotherapy, radiation, or antibody-based treatment for cHL * Prior solid organ transplant * Prior allogeneic stem cell transplantation * Live vaccine within 30 days prior to planned day 1 of protocol therapy (e.g., measles, mumps, rubella, varicella, yellow fever, rabies, bacillus Calmette Guerin \[BCG\], oral polio vaccine, and oral typhoid). Administration of messenger ribonucleic acid (mRNA) vaccines are permitted * Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test within 28 days prior to enrollment is required for female patients of childbearing potential * Lactating females who plan to breastfeed their infants starting with the first dose of study therapy and for at least 6 months after the last treatment * Sexually active patients of reproductive potential who have not agreed to use a highly effective contraceptive method for the duration of their study drug therapy. Following therapy, patients will be advised to use contraception as per institutional practice or as listed below for investigational agents, whichever is longer * Men and women of childbearing potential must continue contraception for a period of 6 months after last dose of brentuximab vedotin * Women of child-bearing potential (WOCBP) must continue contraception for a period of at least 5 months after the last dose of nivolumab * 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

Interventions: PROCEDURE: Biospecimen Collection, BIOLOGICAL: Bleomycin Sulfate, DRUG: Brentuximab Vedotin, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, DRUG: Dacarbazine, DRUG: Doxorubicin Hydrochloride, DRUG: Etoposide, DRUG: Etoposide Phosphate, OTHER: Fludeoxyglucose F-18, RADIATION: Involved-site Radiation Therapy, PROCEDURE: Magnetic Resonance Imaging, BIOLOGICAL: Nivolumab, PROCEDURE: Positron Emission Tomography, DRUG: Prednisolone, DRUG: Prednisone, DRUG: Procarbazine Hydrochloride, OTHER: Questionnaire Administration, DRUG: Vinblastine Sulfate, DRUG: Vincristine Sulfate

Conditions: Lugano Classification Limited Stage Hodgkin Lymphoma AJCC v8

Sites: Children’s Health

I'm interested

Share via email

See this study on ClinicalTrials.gov

A Trial to Study if REGN5837 in Combination With Odronextamab is Safe for Participants With Aggressive B-cell Non-Hodgkin Lymphomas (ATHENA-1)

Description:

The study is researching an experimental drug called REGN5837 in combination with another experimental drug, odronextamab. The aim of the study is to see how safe and tolerable the study drugs are, and to define the recommended dose for phase 2 for the combination. The study is focused on patients with relapsed or refractory aggressive B-cell non-Hodgkin lymphomas (B-NHLs). The study is looking at several other research questions, including: * What side effects may happen from taking the study drugs * How much study drug is in your blood at different times * Whether the body makes antibodies against the study drugs (that could make the drugs less effective or could lead to side effects) * To find out how well the study drugs work against relapsed or refractory aggressive B-cell non-Hodgkin lymphomas (B-NHLs)

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Farrukh Awan

Gender: ALL

Age: 18 Years and over

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05685173

IRB Number: STU-2023-0841

Show full eligibility criteria

Interventions: DRUG: Odronextamab, DRUG: REGN5837

Conditions: B-cell Non-Hodgkins Lymphoma (B-NHL), Non-Hodgkins Lymphoma

Keywords: Aggressive B-Cell Non-Hodgkin Lymphomas

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

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)

Description:

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.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Praveen Ramakrishnan Geethakumari

Gender: ALL

Age: 18 Years and over

Phase: PHASE3

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05605899

IRB Number: STU-2023-0133

Show full eligibility criteria

Key

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.

Interventions: BIOLOGICAL: Axicabtagene Ciloleucel, DRUG: Cyclophosphamide, DRUG: Fludarabine, DRUG: Etoposide, DRUG: Rituximab, DRUG: Doxorubicin, DRUG: Vincristine, DRUG: Prednisone

Conditions: High-risk Large B-cell Lymphoma (LBCL)

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

Study of SGR-1505 in Mature B-Cell Neoplasms

Description:

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.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Heather Wolfe

Gender: All

Age: 18 Years and over

Phase: Phase 1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05544019

IRB Number: STU-2023-0636

Show full eligibility criteria

Interventions: Drug: SGR-1505

Conditions: Mature B-Cell Neoplasm, Non Hodgkin Lymphoma, DLBCL, Waldenström Macroglobulinemia, MALT Lymphoma, Follicular Lymphoma, Pediatric-Type Follicular Lymphoma, IRF4 Gene Rearrangement, EBV-Positive DLBCL, Nos, Burkitt Lymphoma, Plasmablastic Lymphoma, High-grade B-cell Lymphoma, Primary Cutaneous Follicle Center Lymphoma, Primary Effusion Lymphoma, Mantle Cell Lymphoma, DLBCL Germinal Center B-Cell Type, Primary Mediastinal Large B Cell Lymphoma, T-Cell/Histiocyte Rich Lymphoma, ALK-Positive Large B-Cell Lymphoma, Primary Cutaneous Diffuse Large B-Cell Lymphoma, Splenic Marginal Zone Lymphoma, Chronic Lymphocytic Leukemia, Nodal Marginal Zone Lymphoma, HHV8-Positive DLBCL, Nos, Lymphoplasmacytic Lymphoma, Duodenal-Type Follicular Lymphoma, Lymphoid Leukemia, Non-Hodgkins Lymphoma

Keywords: MALT1, NF-kB

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

A Study to Evaluate Adverse Events of Subcutaneous (SC) Epcoritamab Administered in the Outpatient Setting in Adult Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma and Classic Follicular Lymphoma

Description:

B-cell Lymphoma is an aggressive and rare cancer of a type of immune cells (a white blood cell responsible for fighting infections). Classic Follicular Lymphoma is a slow-growing type of non-Hodgkin lymphoma. The purpose of this study is to assess the safety of epcoritamab in adult participants in relapsed or refractory (R/R) diffuse large b-cell lymphoma (DLBCL) who have received at least 1 prior line of systemic antilymphoma therapy including at least 1 anti-CD20 monoclonal antibody-containing therapy or R/R classic follicular lymphoma (cFL). Adverse events will be assessed. Epcoritamab is an investigational drug being developed for the treatment of R/R DLBCL and R/R cFL. Study doctors will assess participants in a monotherapy treatment arm of epcoritamab. Participants will receive escalating doses of epcoritamab, until full dose is achieved. Approximately 184 adult participants with R/R DLBCL and R/R cFL will be enrolled in the study in approximately 80 sites in the United States of America. Participants will receive escalating doses of subcutaneous epcoritamab, until full dose is achieved, 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.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Farrukh Awan

Gender: ALL

Age: 18 Years and over

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05451810

IRB Number: STU-2023-0293

Show full eligibility criteria

Inclusion Criteria:

* Life expectancy \>3 months on standard of care (SOC) treatment. * Meets the following disease activity criteria: -- Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL): * Documented CD20+ mature B-cell neoplasm according to the the 5th edition of World Health Organization (WHO) classification of Haematolymphoid Tumours, based on most recent representative pathology report; * Diffuse large B-cell lymphoma, not otherwise specified (NOS) (de novo or transformed from follicular lymphoma (FL) or Marginal Zone Lymphoma \[MZL\]); * High-grade B-cell Lymphoma including "double-hit" or "triple-hit" DLBCL (technically classified in WHO 2022 or 2016 as high-grade B-cell lymphoma \[HGBCL\], with MYC and BCL2 and/or BCL6 translocations). * Follicular large B-cell lymphoma (FLBL, formerly FL grade 3B); * Relapsed or refractory disease and previously treated with at least 1 prior systemic antineoplastic therapies including at least 1 anti-CD20 monoclonal antibody-containing therapy; Note: Relapsed disease is defined as disease that previously responded to therapy but progressed \>= 6 months after completion of therapy. Refractory disease is defined as disease that either progressed during therapy, failed to achieve an objective response to prior therapy, or progressed within 6 months after completion of therapy (including maintenance therapy). * Either failed prior autologous hematopoietic stem cell transplantation (HSCT), or ineligible for autologous HSCT including but not limited to age, Eastern Cooperative Oncology Group (ECOG) performance status, participant decision, comorbidities and/or insufficient response to prior treatment. * R/R Follicular Lymphoma: * Documented CD20+ mature B-cell neoplasm according to the 5th edition of WHO classification of Haematolymphoid Tumours, based on representative pathology report; --- Classic FL (cFL) (previously FL grade 1, 2, or 3a) without clinical or pathological evidence of transformation; * Relapsed or refractory disease and previously treated with at least 2 prior lines of systemic antineoplastic therapies including at least 1 anti-CD20 monoclonal antibody containing therapy; Note: Relapsed disease is defined as disease that previously responded to therapy but progressed \>= 6 months after completion of therapy. Refractory disease is defined as disease that either progressed during therapy, failed to achieve an objective response to prior therapy, or progressed within 6 months after completion of therapy (including maintenance therapy). * Previously treated with an alkylating agent or lenalidomide; * Relapsed or refractory to the last prior line therapy. Previous lymphoma therapy is defined as 1 of the following: At least 2 months of single-agent therapy, at least 2 consecutive cycles of combination therapy, autologous HSCT, immunomodulatory therapy, or radioimmunotherapy. * Has at least one target lesion defined as: * \>= 1 measurable nodal lesion (long axis \> 1.5 cm) and/or \>= 1 measurable extranodal lesion (long axis \> 1.0 cm) on CT (or MRI) AND * FDG PET scan demonstrating positive lesion(s) compatible with CT (or MRI) defined anatomical tumor sites. * Must have ECOG performance status 0 - 2. * Must have acceptable organ (renal, liver, and hematologic) function within the screening period prior to the first dose of study drug: * Absolute neutrophil count (ANC) \>= 1.0 × 10\^9/L (growth factor support allowed in case of bone marrow involvement, but participant must have not received growth factor within 14 days prior to screening lab collection); * Hemoglobin \>= 8.0 g/dL (RBC transfusions permitted, but participants must not have received blood transfusions within 7 days prior to Screening lab collection); * Platelet count \>= 75 × 10\^9/L, or \>= 50 × 10\^9/L in the presence of bone marrow involvement or splenomegaly (platelet transfusions are permitted, but participants must not have received blood transfusions within 7 days prior to Screening lab collection); * International normalized ratio (INR) (or Prothrombin Time \[PT\]) and aPTT \<= 1.5 × upper limit of normal (ULN), unless receiving anticoagulation * Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) \<= 3.0 × upper limit of normal (ULN); unless due to hepatic involvement of disease or non-hepatic origin. For participants with hepatic involvement of disease, serum AST and serum ALT \<= 5.0 × ULN * Direct bilirubin \<= 2 × ULN; * Estimated creatine clearance (CrCl) as calculated by Cockcroft-Gault Formula \>= 45 mL/min, or estimated glomerular filtration rate (eGFR) as calculated by Modification of Diet in Renal Disease \[MDRD\] equation \>= 45 mL/min; * Lymphocyte count \< 5 × 10\^9/L.

Exclusion Criteria:

* Have a primary central nervous system (CNS) lymphoma or known CNS involvement by lymphoma including leptomeningeal disease, at screening as confirmed by magnetic resonance imaging (MRI)/computed tomography (CT) scan (brain) and, if clinically indicated, by lumbar puncture. * Uncontrolled Human Immunodeficiency Virus (HIV) infection. HIV viral load that is undetectable and controlled with medication for at least 1 year prior to enrollment is allowed. Note: If participant has no history of HIV infection, HIV testing does not need to be conducted at screening unless it is required per local guidelines or institutional standards.

Interventions: DRUG: Epcoritamab

Conditions: Diffuse Large B-Cell Lymphoma, Classic Follicular Lymphoma

Keywords: Relapsed or Refractory Diffuse Large B-Cell Lymphoma, Relapsed or Refractory Classic Follicular Lymphoma, Non-Hodgkins Lymphoma, Cancer, Epcoritamab, ABBV-GMAB-3013, EPCORE

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

A Study of CNTY-101 in Participants With CD19-Positive B-Cell Malignancies (ELiPSE-1)

Description:

ELiPSE-1 is a Phase 1, multi-center, dose-finding study to evaluate the safety, pharmacokinetics, and preliminary efficacy of CNTY-101 in participants with relapsed or refractory cluster of differentiation (CD)19-positive B-cell malignancies.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Praveen Ramakrishnan Geethakumari

Gender: ALL

Age: 18 Years and over

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05336409

IRB Number: STU-2023-0405

Show full eligibility criteria

Interventions: BIOLOGICAL: CNTY-101, BIOLOGICAL: IL-2, DRUG: Lymphodepleting Chemotherapy

Conditions: R/R CD19-Positive B-Cell Malignancies, Indolent Non-hodgkin Lymphoma, Aggressive Non-Hodgkin Lymphoma

Keywords: Lymphoma, Non-Hodgkin, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone, Cellular therapy, Cell therapy, CNTY-101, Century Therapeutics, Induced pluripotent stem cells, CAR-NK, NK cell

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

Study of the Adverse Events and Change in Disease State of Pediatric Participants (and Young Adults Between the Ages of 18-25) With Relapsed/Refractory Aggressive Mature B-cell Neoplasms Receiving Subcutaneous (SC) Injections of Epcoritamab

Description:

The most common types of mature B-cell lymphomas (MBLs) in children are Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). Initial treatment cures 90% - 95% of children with these malignancies, leaving a very small population of relapsed/refractory disease with a poor prognosis. The purpose of this study is to assess the safety and tolerability of epcoritamab in pediatric participants with relapsed/refractory aggressive mature B-cell neoplasms and young adult participants with Burkitt's or Burkitt-like lymphoma/leukemia. Adverse events and change in disease activity will be assessed. Epcoritamab is an investigational drug being developed for the treatment of relapsed/refractory aggressive mature B-cell neoplasms. Participants will receive subcutaneous (SC) of epcoritamab. Approximately 15 pediatric participants with a diagnosis of relapsed/refractory aggressive mature B-cell neoplasms and and young adult participants, ages of 18-25, with a diagnosis of Burkitt's or Burkitt-like lymphoma/leukemia will be enrolled at 50 sites globally. Participants will receive subcutaneous epcoritamab in 28-day cycles. Participants will be followed for a minimum of 3 years after enrollment. 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.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Tamra Slone

Gender: ALL

Age: 1 Year to 25 Years old

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05206357

IRB Number: STU-2022-1118

Show full eligibility criteria

Inclusion Criteria:

* Participants \>= 1 and \< 18 years old at time of primary diagnosis with Burkitt's or Burkitt-like lymphoma/leukemia, diffuse large B-cell lymphoma (DLBCL), or other aggressive mature (CD20+) B-cell lymphomas. Participants up to 25 years of age with Burkitt's or Burkitt-like lymphoma/leukemia are also eligible. * Disease pathologically confirmed (tumor tissue) by local testing. * Relapsed or primary refractory disease meeting any of the following criteria: * Progressive disease at any time during second-line chemoimmunotherapy (CIT). * Best response of stable disease (SD) after a minimum of 2 cycles of second-line CIT. * Best response of partial response (PR) after a minimum of 3 cycles of second-line CIT. * Complete Response (CR) after a minimum of 3 cycles of second-line CIT therapy but unfit or ineligible for consolidation with cell therapy. * Not in CR and unable to initiate or tolerate (i.e., must discontinue) second-line CIT. * Have received cell therapy (allogeneic or autologous transplant or chimeric antigen receptor T-cell (CAR-T) therapy) as consolidation but have not obtained or maintained a CR. * Recovery from toxic effects of prior chemoimmunotherapy. * Performance status by Lansky (\< 16 years old at evaluation) or Karnofsky (\>= 16 years old at evaluation) score \>= 50 or Eastern Cooperative Oncology Group (ECOG) score \<= 2 . * Adequate bone marrow, hepatic, and renal function.

Exclusion Criteria:

* Known central nervous system (CNS) involvement by lymphoma at screening as confirmed by screening magnetic resonance imaging (MRI)/computed tomography (CT)/positron emission tomography (PET) brain scans (participants with evidence of CNS disease only in the cerebrospinal fluid (CSF) will be eligible). * Other malignancy requiring therapy. * Currently receiving anti-cancer therapy, including chemotherapy (excluding intrathecal therapy), radiotherapy, small molecules, monoclonal antibodies, cell therapy, or other investigational agents.

Interventions: DRUG: Epcoritamab

Conditions: Non-hodgkin Lymphoma

Keywords: Non-hodgkin Lymphoma, ABBV-GMAB-3013, Epcoritamab, Burkitt's or Burkitt-like Lymphoma/Leukemia, Diffuse Large B-cell Lymphoma, Aggressive Mature (CD20+) B-cell Lymphoma, Cancer, Relapsed/Refractory Aggressive Mature B-cell Neoplasms, EPCORE

Sites: Children’s Health

I'm interested

Share via email

See this study on ClinicalTrials.gov

Study of ONO-4685 in Patients With Relapsed or Refractory T Cell Lymphoma

Description:

This study will investigate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ONO-4685 in patients with relapsed or refractory T cell Lymphoma

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Praveen Ramakrishnan Geethakumari

Gender: ALL

Age: 18 Years and over

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05079282

IRB Number: STU-2022-0424

Show full eligibility criteria

Inclusion Criteria
• Patients aged ≥ 18 years at time of screening
• Written informed consent by the patient or the patients' legally authorized representative prior to screening
• Patients with histologically or cytologically confirmed diagnosis of one of the following subtypes of T-cell lymphoma:
• Peripheral T-cell lymphoma (PTCL): Angioimmunoblastic T-cell lymphoma (AITL), PTCL, not otherwise specified (PTCL-NOS), nodal PTCL with T-follicular helper (TFH) and follicular T-cell lymphoma (FTCL)
• Cutaneous T-cell lymphoma (CTCL) (stages II-B, III, and IV): Mycosis fungoides (MF) and Sezary syndrome (SS)
• Patients must have received at least 2 prior systemic therapies
• Patients with PTCL must have at least 1 measurable lesion (Cheson BD, 2014)
• Patients with CTCL must have assessable disease by response criteria for CTCL (Olsen EA, 2011)
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) = 0-2
• Life expectancy of at least 3 months
• Adequate bone marrow, renal and hepatic functions

Exclusion Criteria:

• Patients with central nervous system (CNS) involvement
• Patients with Adult T-cell leukemia/lymphoma (ATLL)
• Prior allogeneic stem cell transplant
• Prior treatment with ONO-4685, anti-PD-1, anti-PD-L1, anticytotoxic T lymphocyte associated protein 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
• Prior allogeneic and autologous chimeric antigen receptor (CAR) T-cell therapy
• Patients with malignancies (other than T-cell lymphoma) except for completely resected basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, or any other malignancies that has not relapsed for at least 2 years
• History of severe allergy or hypersensitivity to any monoclonal antibodies, other therapeutic proteins or corticosteroid (e.g., dexamethasone)
• History of infection with Mycobacterium tuberculosis within 2 years prior to the first dose of study treatment
• Patients with systemic and active infection including human immunodeficiency virus (HIV), hepatitis B or C virus infection
• Patients not recovered to Grade 1 or stabilized from the adverse effects (excluding alopecia) of any prior therapy for their malignancies
• Women who are pregnant or lactating

Interventions: DRUG: ONO-4685

Conditions: Relapsed or Refractory T Cell Lymphoma, Lymphoid Leukemia

Keywords: ONO-4685, PD-1, CD3, Bispecific antibody, PTCL, AITL, PTCL-NOS, nodal PTCL with TFH, FTCL, CTCL, MF, SS

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

An Open-Label, Phase 2 Trial of Nanatinostat in Combination With Valganciclovir in Patients With Epstein-Barr Virus-Positive (EBV+) Relapsed/Refractory Lymphomas (NAVAL-1)

Description:

A Phase 2 study to evaluate the efficacy of nanatinostat in combination with valganciclovir in patients with relapsed/refractory EBV-positive lymphomas

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Farrukh Awan

Gender: ALL

Age: 18 Years and over

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT05011058

IRB Number: STU-2022-0417

Show full eligibility criteria

Interventions: DRUG: Nanatinostat in combination with valganciclovir

Conditions: Epstein-Barr Virus Associated Lymphoproliferative Disorder, EBV-Related PTLD, EBV Related Non-Hodgkin's Lymphoma, EBV-Positive DLBCL, Nos, EBV Associated Lymphoma, EBV Related PTCL, Nos, Lymphoid Leukemia

Keywords: EBV positive post-transplant lymphoproliferative disorder (PTLD), EBV lymphoma, Lymphoproliferative Disorders, Epstein-Barr Virus (EBV), EBV positive T cell lymphoma, EBV positive diffuse large B-cell lymphoma (DLBCL), EBV positive peripheral T-cell lymphoma (PTCL), EBV positive PTLD in Pediatrics

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma

Description:

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.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Laura Klesse

Gender: ALL

Age: 12 Months to 30 Years old

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT04870944

IRB Number: STU-2023-0600

Show full eligibility criteria

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

Interventions: PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspirate, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Echocardiography, DRUG: FACT Complex-targeting Curaxin CBL0137

Conditions: Diffuse Midline Glioma, H3 K27M-Mutant, Metastatic Malignant Neoplasm in the Central Nervous System, Recurrent Diffuse Intrinsic Pontine Glioma, Recurrent Lymphoma, Recurrent Malignant Solid Neoplasm, Recurrent Osteosarcoma, Recurrent Primary Malignant Central Nervous System Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Osteosarcoma, Refractory Primary Malignant Central Nervous System Neoplasm

Sites: Children’s Health

I'm interested

Share via email

See this study on ClinicalTrials.gov

DALY II USA/ MB-CART2019.1 for DLBCL

Description:

DALY II USA is a phase II, multi-center, single arm study to evaluate the efficacy, safety, and pharmacokinetics of zamtocabtagene autoleucel (MB-CART2019.1) in patients with relapsed and/or refractory diffuse large B cell lymphoma (DLBCL) after receiving at least two lines of therapy.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Farrukh Awan

Gender: All

Age: 18 Years and over

Phase: Phase 2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT04792489

IRB Number: STU-2022-0110

Show full eligibility criteria

Inclusion Criteria:

• Histologically confirmed DLBCL or associated subtype, defined by WHO 2016 classification:
• CNS Cohort only: B-cell primary or secondary central nervous system lymphoma (PCNSL or SCNSL)
• Relapsed or refractory disease after 2 or more lines of chemotherapy including rituximab and anthracycline and either having failed autologous stem cell transplant (ASCT), or ineligible, not intended for or not consenting to ASCT
• Chemotherapy-refractory disease is defined as persistent disease after last line of therapy or relapsed or persistent disease after prior ASCT for lymphoma
• Disease relapse in subjects without prior ASCT is defined as relapse of disease after the last dose of most recent therapy regimen
• CNS Cohort: Subjects with relapsed/refractory PCNSL that have failed (or unable to tolerate) first-line therapy.
• CNS Cohort: Subjects with SCNSL must have relapsed or refractory disease after having received at least 1 prior line of systemic therapy
• Age ≥18 years
• Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at screening. ECOG performance status of 2 at screen is allowed if the decrease in performance status is due to DLBCL
• Measurable disease according to Lugano 2014 criteria for assessing FDG-PET/CT in lymphoma (Cheson et al, 2014) for DLBCL and SCNSL while IPCG criteria for the primary PCNSL.
• Subject must have a tumor biopsy sample (at least 16 unstained slides of tissue or tissue block) from the most recent relapse available prior to MB-CART2019.1 infusion. If medically not feasible to obtain a biopsy from the most recent relapse and for cases when the amount of tissue is limited, the sponsor should be consulted, to confirm adequacy of the sample for study required analyses
• No clinical suspicion of central nervous system (CNS) lymphoma (not applicable to CNS cohort)
• If the subject has history of CNS disease (not applicable to CNS cohort), then he/she must have no signs or symptoms of CNS disease, have no active disease on magnetic resonance imaging (MRI), have no large cell lymphoma present in cerebral spinal fluid (CSF) on cytospin preparation and flow cytometry, regardless of the number of white blood cells (WBCs)
• If has history of cerebral vascular accident (CVA), the CVA event must be greater than 12 months prior to leukapheresis. Any neurological deficits must be stable.
• A creatinine clearance (as estimated by direct urine collection or Cockcroft-Gault Equation) > 45mL/min
• Cardiac ejection fraction (EF) ≥ 45% as determined by an echocardiogram (ECHO) or Multigated Radionuclide Angiography (MUGA)
• Resting O2 saturation >90% on room air
• Serum alanine aminotransferase (ALT) / aspartate aminotransferase (AST) <5 times the Upper Limit of Normal (ULN) for age
• Total bilirubin <1.5 mg/dl, except in individuals with Gilbert's syndrome
• Absolute neutrophil count (ANC) > 1000/μL
• Absolute lymphocyte count > 100/μL
• Platelet count > 50,000/µL
• Estimated life expectancy of more than 3 months other than primary disease

Exclusion Criteria:

• Primary CNS lymphoma (not applicable to CNS cohort)
• Richter's transformed DLBCL arising from chronic lymphocytic leukemia (CLL)
• Unable to give informed consent
• Known history of infection with human immunodeficiency virus (HIV) or active hepatitis B (HBsAg positive). If there is a history of treated hepatitis B or hepatitis C, the viral load must be quantitative polymerase chain reaction (PCR) negative; antiviral prophylaxis is required if HBsAg negative and anti-HBc positive.
• Known history of infection with hepatitis C virus (anti-HCV positive) unless viral load is undetectable per quantitative PCR and/or nucleic acid testing.
• Seizure that is not effectively controlled pharmacologically.
• Known history of CVA within prior 12 months.
• Known history or presence of autoimmune CNS disease, such as multiple sclerosis, optic neuritis, or other immunologic or inflammatory disease
• Presence of CNS disorder that, in the judgment of the investigator, may impair the ability to evaluate neurotoxicity. For CNS Cohort: Bulky leptomeningeal disease and or CSF protein >100 mg/Dl. Recent (within 2 months) whole brain radiotherapy (WBRT)
• Active systemic fungal, viral, or bacterial infection
• Pregnant or breast-feeding woman
• Previous or concurrent malignancy with the following exceptions:
• Adequately treated basal cell or squamous cell carcinoma (adequate wound healing required prior to study entry)
• In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 2 years prior to the study
• Adequately treated breast or prostate carcinoma on hormonal therapies such as Lupron or tamoxifen and in clinical remission of ≥ 2 years
• A primary malignancy which has been completely resected / treated with curative intent and in complete remission of ≥ 2 years
• Immunocompromised subjects e.g., due to current treatment of non-neurologic autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus).
• Medical condition requiring prolonged use of systemic corticosteroids equivalent to prednisone >10 mg/day
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months of enrollment
• Concurrent radiotherapy (normal tissue sparing palliative radiotherapy allowed up to time of lymphodepletion). For systemic therapy, at least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed at the time of scheduled leukapheresis.
• Baseline dementia that would interfere with therapy or monitoring, determined using Immune Effector Cell-Associated Encephalopathy (ICE) Assessment at baseline
• History of severe immediate hypersensitivity reaction to any of the agents used in this study
• Refusal to participate in additional lentiviral gene therapy LTFU protocol
• Prior CAR-T therapy for any indication or systemic gene modifying therapy for DLBCL
• Prior allogeneic stem cell transplant for any indication
• Prior BITE antibodies for cancer therapy
• Prior T cell receptor-engineered T cell therapy

Interventions: Biological: zamtocabtagene autoleucel (MB-CART2019.1), Drug: Cyclophosphamide, Drug: Fludarabine, Drug: Bendamustine

Conditions: Refractory Diffuse Large B Cell Lymphoma (DLBCL), Relapsed Diffuse Large B Cell Lymphoma, High Grade B-cell Lymphoma (HGBCL), Primary Mediastinal B-cell Lymphoma (PMBCL), Transformed Lymphoma, Central Nervous System Lymphoma, Non-Hodgkins Lymphoma

Keywords: CD19/CD20-directed CAR-T Cells, Zamtocabtagene autoleucel, B-Cell Non-Hodgkin Lymphoma, Primary Central Nervous System Lymphoma, Secondary Central Nervous System Lymphoma, NHL, PCNSL, SCNSL, Chimeric Antigen Receptor, CAR, CAR-T Cell, Autologous T Cell Therapy, Central Nervous System Neoplasms, Lymphoma, Lymphoma, Non-Hodgkin, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

Nivolumab in Combination With Chemo-Immunotherapy for the Treatment of Newly Diagnosed Primary Mediastinal B-Cell Lymphoma

Description:

This phase III trial compares the effects of nivolumab with chemo-immunotherapy versus chemo-immunotherapy alone in treating patients with newly diagnosed primary mediastinal B-cell lymphoma (PMBCL). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Treatment for PMBCL involves chemotherapy combined with an immunotherapy called rituximab. Chemotherapy drugs 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. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Giving nivolumab with chemo-immunotherapy may help treat patients with PMBCL.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Laura Klesse

Gender: ALL

Age: 2 Years and over

Phase: PHASE3

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT04759586

IRB Number: STU-2021-0574

Show full eligibility criteria

Inclusion Criteria:

* Age \>= 2 years * Patient must have histologically confirmed primary mediastinal B-cell lymphoma (PMBCL) as defined by World Health Organization (WHO) criteria * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 or ECOG performance status of 3 if poor performance is related to lymphoma * Children's Oncology Group (COG) Institutions: Use Karnofsky for patients \>= 17 and \< 18 years of age and Lansky for patients \< 17 years of age * Adults (age 18 or older): Creatinine clearance \>= 30 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on actual body weight * Pediatric Patients (age \< 18 years): The following must have been obtained within 14 days prior to registration: * Measured or calculated (based on institutional standard) creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 ml/min/1.73 m\^2, or * Serum creatinine =\< 1.5 x institutional upper limit of normal (IULN), or a serum creatinine based on age/gender as follows: * Age : 2 to \< 6 year; Maximum serum creatinine (mg/dL): 0.8 (male; 0.8 (female) * Age : 6 to \< 10 years; Maximum serum creatinine (mg/dL): 1 (male); 1 (female) * Age : 10 to \< 13 years; Maximum serum creatinine (mg/dL): 1.2 (male); 1.2 (female) * Age : 13 to \< 16 years; Maximum serum creatinine (mg/dL): 1.5 (male); 1.4 (female) * Age : \>= 16 years to \< 18 years; Maximum serum creatinine (mg/dL): 1.7 (male); 1.4 (female) * Patients with abnormal liver function will be eligible to enroll if the lab abnormality is thought to be due to the lymphoma or Gilbert's syndrome * Age \>= 18 years: Ejection fraction of \>= 50% by echocardiogram * Age \< 18 years: Shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \>= 50% by radionuclide angiogram * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated * Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load * 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

Exclusion Criteria:

* Administration of prior anti-cancer therapy except as outlined below: * A short course (=\< 2 weeks) of corticosteroids for the relief of lymphoma-related symptoms * A single course of COP (cyclophosphamide, vincristine, and prednisone) * One cycle of chemo-immunotherapy including R-CHOP, DA-EPOCH-R, a pediatric mature B-cell non-Hodgkin lymphoma (B-NHL) induction therapy (such as ANHL1131), or intrathecal chemotherapy that has not started more than 21 days prior to enrollment * Active ischemic heart disease or heart failure * Active uncontrolled infection * Central nervous system (CNS) involvement of lymphoma * Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with safety or efficacy assessment of this trial * Active autoimmune disease that has required systemic treatment (such as disease modifying agents, corticosteroids, or immunosuppressive agents) in the past 2 years. Replacement therapy such as thyroxine, insulin or physiologic corticosteroid for adrenal or pituitary insufficiency is not considered a form of systemic treatment * In patients \< 18 years of age hepatitis B serologies consistent with past or current infections * Patients with severe hepatic impairment (Child-Pugh class C or serum total bilirubin \> 5.0 mg/dL) unless thought to be due to lymphoma or Gilbert's syndrome * 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 * Sexually active patients of reproductive potential who have not agreed to use a highly effective contraceptive method (failure rate of \< 1% per year when used consistently and correctly) for the duration of their study participation * Lactating females are not eligible unless they have agreed not to breastfeed their infants starting with the first dose of study therapy and for at least 6 months after the last dose of rituximab

Interventions: PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, DRUG: Doxorubicin Hydrochloride, PROCEDURE: Echocardiography, DRUG: Etoposide Phosphate, BIOLOGICAL: Filgrastim, PROCEDURE: Lumbar Puncture, BIOLOGICAL: Nivolumab, BIOLOGICAL: Pegfilgrastim, PROCEDURE: Positron Emission Tomography, DRUG: Prednisolone, DRUG: Prednisone, RADIATION: Radiation Therapy, BIOLOGICAL: Rituximab, BIOLOGICAL: Rituximab and Hyaluronidase Human, DRUG: Vincristine Sulfate

Conditions: Primary Mediastinal Large B-cell Lymphoma

Sites: Children’s Health

I'm interested

Share via email

See this study on ClinicalTrials.gov

Efficacy and Safety of Nemtabrutinib (MK-1026) in Participants With Hematologic Malignancies (MK-1026-003)

Description:

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).

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Farrukh Awan

Gender: ALL

Age: 18 Years and over

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT04728893

IRB Number: STU-2023-0815

Show full eligibility criteria

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 to eliminate study intervention 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 and J) * 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 * Part 2 Cohort J: CLL/SLL participants whose disease relapsed or was refractory to prior therapy with a covalent/irreversible BTKi and BCL2i * 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 meets the following prior therapy requirements: * 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

Interventions: DRUG: Nemtabrutinib

Conditions: Hematologic Malignancies, Waldenstroms Macroglobulinaemia, Non-Hodgkins Lymphoma, Chronic Lymphocytic Leukaemia

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

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

Description:

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.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Kathleen Ludwig

Gender: ALL

Age: up to 22 Years old

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT04726241

IRB Number: STU-2022-0170

Show full eligibility criteria

Interventions: PROCEDURE: Biospecimen Collection

Conditions: Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Acute Myeloid Leukemia Post Cytotoxic Therapy, Juvenile Myelomonocytic Leukemia, Mixed Phenotype Acute Leukemia, Myelodysplastic Syndrome, Myelodysplastic Syndrome Post Cytotoxic Therapy, Myeloid Leukemia Associated With Down Syndrome

Sites: Children’s Health

I'm interested

Share via email

See this study on ClinicalTrials.gov

Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome (EPCORE™ CLL-1)

Description:

The study is a global, multi-center safety and efficacy trial of epcoritamab, an antibody also known as EPKINLY™ and GEN3013 (DuoBody®-CD3xCD20). Epcoritamab will either be studied as: - Monotherapy, or - Combination therapy: - epcoritamab + venetoclax - epcoritamab + lenalidomide - epcoritamab + R-CHOP (i.e., rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine and prednisone). The study includes patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL)/small lymphocytic lymphoma (SLL) and patients with Richter's Syndrome (RS). Study participants with R/R CLL/SLL are treated either with epcoritamab as monotherapy or epcoritamab + venetoclax. Study participants with RS are treated either with epcoritamab as monotherapy or epcoritamab + lenalidomide or epcoritamab + R-CHOP. The trial consists of two parts, a dose-escalation phase (phase Ib) and an expansion phase (phase II). Patients with RS are only included in the expansion phase.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Farrukh Awan

Gender: All

Age: 18 Years and over

Phase: Phase 1/Phase 2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT04623541

IRB Number: STU-2020-1263

Show full eligibility criteria

Key Inclusion Criteria
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
• Evidence of CD20 positivity in a sample representative of the disease at Screening.
• Acceptable hematology parameters and organ function based on baseline bloodwork.
• For R/R CLL arms - Must have active CLL/SLL disease requiring treatment per iwCLL 2018 criteria.
• For R/R CLL arms - Received at least 2 prior lines of systemic anti-neoplastic therapy including a Bruton's tyrosine kinase (BTK) inhibitor.
• For all RS arms - Have tumor biopsy-proven CD20+ Diffuse large B-cell Lymphoma (DLBCL) and a clinical history of CLL/SLL.
• For all RS arms - Must have measurable disease by fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) or magnetic resonance imaging (MRI) scan.
• For all RS arms - Must provide mandatory formalin-fixed, paraffin-embedded (FFPE) tumor biopsy sample.
• Life expectancy >3 months on standard of care (SOC).
• For RS - monotherapy arm: Deemed as ineligible for chemoimmunotherapy at investigator's discretion or participant who refuses to receive intensive chemotherapy
• For RS - lenalidomide combination therapy arm
• Deemed as ineligible for chemoimmunotherapy at the investigator's discretion, or participant who refuses to receive intensive chemotherapy.
• Eligible for treatment with lenalidomide.
• Must be willing to use contraception and adhere to the Lenalidomide Pregnancy Risk Minimization Plan
• For RS - R-CHOP combination Therapy Arm -
• Eligible for treatment with R-CHOP.
• For R/R CLL - venetoclax combination Therapy arm - after receiving at least 1 prior line of systemic antineoplastic therapy. Key Exclusion Criteria
• Received prior treatment with a CD3×CD20 bispecific antibody.
• Received any prior allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation.
• Received (CAR) T-cell therapy within 100 days or an investigational drug within 4 weeks, prior to first dose of epcoritamab.
• Autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy.
• Received vaccination with live vaccines within 28 days.
• Clinically significant cardiac disease.
• Known current malignancy other than inclusion diagnosis.
• Has had major surgery within 4 weeks.
• Active hepatitis B virus or active hepatitis C.
• Known history of HIV.
• For R/R CLL arms - Any history of RS or evidence indicating a potential Richter's transformation.
• Received venetoclax within 24 months prior to beginning venetoclax ramp-up for this trial and progressed on treatment.
• For all RS arms - Diagnosis of Richter's syndrome not of the DLBCL subtype such as Hodgkin's lymphoma, prolymphocytic leukemia.
• RS - Lenalidomide Combination Therapy and RS Monotherapy Arms - received more than 2 prior lines of therapy for RS. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Interventions: Biological: Epcoritamab, Biological: Epcoritamab, Drug: rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone, Drug: Venetoclax, Biological: Epcoritamab, Drug: Lenalidomide

Conditions: Relapsed/Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Richter's Syndrome, Lymphoid Leukemia

Keywords: DuoBody®, Bispecific antibodies, Anti-CD3, Anti-CD20

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

Testing the Addition of Lenalidomide and Nivolumab to the Usual Treatment for Primary CNS Lymphoma

Description:

This phase I trial tests the safety, side effects, best dose and effectiveness of lenalidomide when added to nivolumab and the usual drugs (rituximab and methotrexate) in patients with primary central nervous system (CNS) lymphoma. Lenalidomide may stop or slow primary CNS lymphoma by blocking the growth of new blood vessels necessary for tumor growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Methotrexate is frequently combined with other chemotherapy agents to improve response. This study may help increase the understanding of lenalidomide and nivolumab use in primary CNS lymphoma treatment. In addition, it may help researchers see whether the control of CNS lymphoma can be extended by using these study drugs as maintenance (prolonged therapy) after control is achieved with the initial chemotherapy regimen (induction).

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Praveen Ramakrishnan Geethakumari

Gender: ALL

Age: 18 Years and over

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT04609046

IRB Number: STU-2021-0822

Show full eligibility criteria

Inclusion Criteria:

* Histologically proven primary CNS diffuse large b-cell lymphoma confirmed by one of the following: * Brain biopsy or resection * Cerebrospinal fluid * Vitreous fluid * No prior organ transplantation to exclude post-transplant lymphoproliferative disorders * No prior chemotherapy or radiation therapy for lymphoma * No prior allogeneic stem cell transplantation * Use of systemic corticosteroids (dexamethasone up to 24 mg/day or equivalent) for disease control or improvement of performance status to be tapered as fast as clinically safe after initiation of therapy is permissible * Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown and an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, female of childbearing potential (FCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) =\< 7 days prior to registration * Age \>= 18 years * Karnofsky performance scale (KPS) \>= 40 (\>= 50 for patients older than 60 unless related to lymphoma on investigator's opinion) * Absolute neutrophil count (ANC) \>= 1,500/mm\^3 * Platelet count \>= 100,000/mm\^3 * Calculated creatinine clearance \>= 50 mL/min by Cockcroft-Gault formula * Total Bilirubin =\< 1.5 x upper limit of normal (ULN) * Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =\< 2.5 x upper limit of normal (ULN) * No evidence of non-Hodgkin's lymphoma (NHL) outside CNS * No prior history of NHL * No history of autoimmune disorder. Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as Systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease. Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible * Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event) * Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (except short course of systemic corticosteroids for disease control or improvement of performance status or other immunosuppressive medications within 14 days prior to registration. Inhaled or topical steroids and adrenal replacement doses \< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if \< 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted * Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study * No prior or concurrent malignancies with exception of surgically cured carcinoma in situ (CIS) of the uterus, carcinoma of the skin without evidence of disease for \>= 5 years * No concurrent malignancy requiring active therapy * No untreated hepatitis C virus (HCV) infection with detectable HCV viral load * No untreated chronic hepatitis B virus (HBV) infection with detectable HBV viral load * No untreated human immunodeficiency virus (HIV) infection or with detectable viral load or with CD4+T-cell count of less than 500/mm\^3 * No history of HIV infection and evidence of Epstein Barr virus (EBV)-related primary central nervous system lymphoma (PCNSL) * Inability to tolerate anticoagulation with acetylsalicylic acid, warfarin, or direct oral anticoagulants * No other investigational agent * No history of severe hypersensitivity reaction to any monoclonal antibody * No history of allergic reactions attributed to compounds of similar chemical or biologic composition to or other agents used in study * Sulfonamide drugs, trimethoprim, salicylates, nonsteroidal anti-inflammatory drugs, penicillin, vitamin C, ciprofloxacin, and proton pump inhibitors should be held at least 48 hours prior to methotrexate administration

Interventions: PROCEDURE: Bone Marrow Aspiration and Biopsy, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography, DRUG: Lenalidomide, PROCEDURE: Lumbar Puncture, PROCEDURE: Magnetic Resonance Imaging, DRUG: Methotrexate, BIOLOGICAL: Nivolumab, PROCEDURE: Positron Emission Tomography, BIOLOGICAL: Rituximab, PROCEDURE: Ultrasound Imaging

Conditions: Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

Safety and Efficacy Trial of Epcoritamab Combinations in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL) (EPCORE™ NHL-2)

Description:

The purpose of this trial is to measure the safety and effectiveness of epcoritamab (EPKINLY™), either by itself or together with other therapies, when treating subjects with B-cell non-Hodgkin Lymphoma (B-NHL). The aim of the first part of the trial is to identify the most appropriate dose of epcoritamab, and the aim of the second part of the trial is to assess the selected epcoritamab dose in a larger group of participants with B-NHL. All participants in this trial will receive either epcoritamab alone, or epcoritamab combined with another standard treatment regimen, with a total of 10 different treatment arms being studied. Trial details include: * The total trial duration will be up to 6 years. * The treatment duration for each participant depends upon which arm of treatment they are assigned to receive, but will be no more than 3 years. * The visit frequency for each participant depends upon which arm of treatment they are assigned to receive, but will be weekly to start for all participants, then will decrease to either: every 2 weeks, or every 3 weeks, or every 4 weeks, or every 8 weeks. * All participants will receive active drug; no one will be given placebo. Participants who receive treatment with epcoritamab will have it injected right under the skin. Participants will receive a different regimen of epcoritamab depending upon which arm of treatment they are assigned. Participants who receive standard treatments will have IV infusions and/or oral administration of those treatments. Participants will receive a different standard treatment regimen depending upon which arm of treatment they are assigned. Arm 9 (follicular lymphoma (FL)) is still open for enrolment of new patients, while the other arms have closed their recruitment.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Farrukh Awan

Gender: ALL

Age: 18 Years and over

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT04663347

IRB Number: STU-2021-0153

Show full eligibility criteria

Key Inclusion Criteria
• Measurable disease defined as ≥1 measurable nodal lesion (long axis \>1.5 cm and short axis \>1.0 cm) or ≥1 measurable extra-nodal lesion (long axis \>1.0 cm) on computed tomography (CT) or magnetic resonance imaging (MRI)
• Eastern Cooperative Oncology Group (ECOG) PS score of 0, 1 or 2
• Acceptable organ function at screening
• CD20-positive non-Hodgkin lymphoma (NHL) at most recent representative tumor biopsy
• If of childbearing potential subject must practicing a highly effective method of birth control
• A man who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control Arm 1: * Newly diagnosed DLBCL * DLBCL, not otherwise specified (NOS) * "Double-hit" or "triple-hit" DLBCL * FL Grade 3B Arm 2: R/R FL Arm 3: Newly diagnosed, previously untreated FL grade 1-3A Arm 4: * Documented R/R DLBCL and eligible for HDT-ASCT * DLBCL, NOS * "Double-hit" or "triple-hit" DLBCL * FL Grade 3B Arm 5: * Documented R/R DLBCL and ineligible for HDT-ASCT * DLBCL, NOS * "Double-hit" or "triple-hit" DLBCL * FL Grade 3B Arm 6: Newly diagnosed, previously untreated FL grade 1-3A Arm 7: * FL Grade 1-3A * If PR or CR per Lugano criteria following first-line or second-line treatment with SOC regimen, and last dose of SOC within 6 months prior to enrollment. Arm 8: * Newly diagnosed DLBCL who are not fit to receive full-dose anthracycline * T-cell/histiocyte rich DLBCL * "Double-hit" or "triple-hit" DLBCL * FL Grade 3B Arm 9: * R/R FL * Progressed within 24 months of initiating first-line treatment Arm 10: * Documented R/R DLBCL and eligible for HDT-ASCT * DLBCL, NOS * "Double-hit" or "triple-hit" DLBCL * FL Grade 3B Key Exclusion Criteria
• Chemotherapy, radiation therapy, or major surgery within 4 weeks prior to the first dose of epcoritamab
• Any prior treatment with a bispecific antibody targeting CD3 and CD20.
• Treatment with CAR-T therapy within 100 days prior to first dose of epcoritamab
• Clinically significant cardiovascular disease
• Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
• CNS lymphoma or known CNS involvement by lymphoma at screening as confirmed by MRI/CT scan of the brain and, if clinically indicated, by lumbar puncture
• Positive tests for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
• Known history of seropositivity of human immunodeficiency virus (HIV)
• Active tuberculosis or history of completed treatment for active tuberculosis within the past 12 months
• Neuropathy \> grade 1
• Receiving immunostimulatory agent
• Prior allogeneic HSCT
• Current seizure disorder requiring anti-epileptic therapy NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Interventions: DRUG: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, DRUG: rituximab and lenalidomide, DRUG: rituximab and bendamustine, DRUG: rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin, DRUG: gemcitabine and oxaliplatin, BIOLOGICAL: Epcoritamab, DRUG: rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone, DRUG: Lenalidomide, DRUG: rituximab, ifosfamide, carboplatin, and etoposide phosphate, BIOLOGICAL: Epcoritamab, BIOLOGICAL: Epcoritamab, BIOLOGICAL: Epcoritamab, BIOLOGICAL: Epcoritamab, BIOLOGICAL: Epcoritamab, BIOLOGICAL: Epcoritamab, BIOLOGICAL: Epcoritamab

Conditions: Diffuse Large B-Cell Lymphoma, Follicular Lymphoma

Keywords: DuoBody®, monoclonal antibodies, anti-CD3, anti-CD20

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

A Study of Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP) with or Without Selinexor in Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma

Description:

The purpose of this Phase 2/3 study is to evaluate efficacy and safety of the combination of selinexor and R-GDP (SR-GDP) in patients with RR DLBCL who are not intended to receive hematopoetic stem cell transplantation (HSCT) or chimeric antigen receptor T cell (CAR-T) therapy. This study consists of 3 arms each in Phase 2 and 3. Phase 2 portion of the study will assess the two doses of selinexor (40 milligram \[mg\] or 60 mg) in combination with R-GDP, for up to 6 cycles (21-day per cycle), followed by 60 mg selinexor single agent continuous therapy for those who have reached a partial or complete response. Phase 3 portion of the study will evaluate the selected dose of SR-GDP (identified in Phase 2) versus standard R-GDP + matching placebo, for up to 6 cycles (21-day per cycle), followed by placebo or 60 mg selinexor single agent continuous therapy for those who have reached partial or complete response.

Contact(s):

studyfinder@utsouthwestern.edu

Principal Investigator:

Gender: ALL

Age: 18 Years and over

Phase: PHASE2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT04442022

Show full eligibility criteria

Inclusion Criteria:

* Have pathologically confirmed de novo DLBCL or DLBCL transformed from previously diagnosed indolent lymphoma (e.g., follicular lymphoma). Patient with high-grade lymphoma with c-MYC, Bcl2 and/or Bcl6 rearrangements are eligible (only for Phase 2). (Documentation to be provided). * Have received at least 1 but no more than 3 prior lines of systemic therapy for the treatment of DLBCL with relapsed or refractory disease following their most recent regimen. * Salvage chemoimmunotherapy followed by stem cell transplantation will be considered as 1 line of systemic therapy. * Maintenance therapy will not be counted as a separate line of systemic therapy. * Radiation with curative intent for localized DLBCL will not be counted as 1 line of systemic therapy. * Positron emission tomography (PET) positive measurable disease with at least 1 node having the longest diameter (LDi) greater than (\>) 1.5 centimeter (cm) or 1 extranodal lesion with LDi \>1 cm (per the Lugano Criteria 2014). The Deauville 5-point scale (D5PS) score assessed on the FDG PET/CT should be between 3 to 5. * Not intended for HSCT or CAR-T cell therapy based on objective clinical criteria determined by the treating physician. Patients who cannot receive HSCT due to active disease are allowed on study (up to approximately 15 percent \[%\] of patients enrolled in each Phase). Documentation on lack of intention to proceed to receive HSCT or CAR-T therapy must be provided by the treating physician. * Adequate bone marrow function at screening, defined as: * Absolute neutrophil count (ANC) ≥1\*10\^9 per liter (/L). * Platelet count ≥100\*10\^9/L (without platelet transfusion less than \[\<\] 14 days prior to Cycle 1 Day 1 \[C1D1\]). * Hemoglobin ≥8.5 gram per deciliter (g/dL) (without red blood cell transfusion \<14 days prior to C1D1). * Circulating lymphocytes less than or equal to (≤) 50\*10\^9/L. * Adequate liver and kidney function, defined as: * Aspartate transaminase (AST) or alanine transaminase (ALT) ≤2.5\*upper limit of normal (ULN), or ≤5\*ULN in cases with known lymphoma involvement in the liver. * Serum total bilirubin ≤2\*ULN, or ≤5\*ULN if due to Gilbert syndrome or in cases with known lymphoma involvement in the liver. * Calculated creatinine clearance (CrCl) ≥30 milliliter per minute (mL/min) based on Cockcroft-Gault formula. * Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. * An estimated life expectancy of \>3 months at Screening. * Patients with primary refractory DLBCL defined as no response or relapse within 6 months after ending first-line treatment, will be allowed in the study. * Agree to highly effective contraception during the duration of the study with contraception use continuing for 12 months after the last dose of study treatment * Female patients of childbearing potential must have a negative serum pregnancy test at Screening and agree to use highly effective methods of contraception throughout the study and for 12 months following the last dose of study treatment (except patients with Non-Childbearing potential: Age \>50 years and naturally amenorrhoeic for \>1 year, or previous bilateral salpingo-oophorectomy, or hysterectomy). * Male patients who are sexually active must use highly effective methods of contraception throughout the study and for 12 months following the last dose of study treatment. Male patients must agree not to donate sperm during the study treatment period and for 12 months following the last dose of study treatment.

Exclusion Criteria:

* DLBCL with mucosa-associated lymphoid tissue (MALT) lymphoma, composite lymphoma (Hodgkin's lymphoma + non-Hodgkin's lymphoma \[NHL\]), DLBCL transformed from diseases other than indolent NHL; primary mediastinal (thymic) large B-cell lymphoma (PMBL); T-cell rich large B-cell lymphoma. * Previous treatment with selinexor or other XPO1 inhibitors. * Contraindication to any drug contained in the combination therapy regimen (SR-GDP). * Known active central nervous system or meningeal involvement by DLBCL at time of Screening. * Use of any standard or experimental anti-DLBCL therapy (including nonpalliative radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancer therapy) \<21 days prior to C1D1 (prednisone \<30 mg or equivalent is permitted; palliative radiation is permitted only if on non-target lesions). * Any AE, by C1D1, which has not recovered to Grade ≤1 (Common Terminology Criteria for Adverse Events \[CTCAE\], v.5.0), or returned to baseline, related to the previous DLBCL therapy, except hematological abnormalities (as specified in the inclusion criteria) and alopecia. * Major surgery \<14 days of Cycle 1 Day 1. * Hematopoietic stem cell transplantation/CAR-T therapy as follows: * Autologous stem cell transplant (SCT) \<100 days or allogeneic-SCT \<180 days prior to C1D1 * Active graft-versus-host disease (GVHD) after allogeneic SCT (or cannot discontinue GVHD treatment or prophylaxis) * CAR-T cell infusion \<90 days prior to Cycle 1 * Neuropathy Grade ≥2 (CTCAE, v.5.0). * Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety, or being compliant with the study procedures. * Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within 7 days prior to first dose of study treatment; however, prophylactic use of these agents is acceptable (including parenteral). * Patient with active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infections: * Patient with active HBV are allowed if antiviral therapy for hepatitis B has been given for \>8 weeks and viral load is \<100 International units (IU)/mL prior to first dose of study treatment. * Patients with known history of HCV or found to be HCV antibody positive on screening, are allowed if there is documentation of negative viral load per institutional standard. * Patients with HIV are allowed if they have a negative viral load per institutional standard, and no history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections in the last year. * Inability to swallow tablets, malabsorption syndrome, or any other gastrointestinal (GI) disease or dysfunction that could interfere with absorption of study treatment. * Breastfeeding or pregnant women. * Inability or unwillingness to sign an informed consent form (ICF). * In the opinion of the Investigator, patient who are significantly below their ideal body weight. * Patients who received a live attenuated vaccine within prior 28 days of the first dose of study treatment.

Interventions: DRUG: Selinexor (combination therapy), DRUG: Selinexor (combination therapy), DRUG: Selinexor (combination therapy), DRUG: Placebo matching for Selinexor (combination therapy), DRUG: Rituximab (combination therapy), DRUG: Rituximab (combination therapy), DRUG: Gemcitabine (combination therapy), DRUG: Dexamethasone (combination therapy), DRUG: Cisplatin (combination therapy), DRUG: Selinexor (continuous therapy), DRUG: Placebo matching for Selinexor (continuous therapy)

Conditions: Relapsed/Refractory Diffuse Large B-cell Lymphoma

Keywords: Relapsed/Refractory DLBCL, Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP), Selinexor, Karyopharm, KCP-330, XPOVIO, DLBCL, XPORT-DLBCL-030, R-GDP

I'm interested

Share via email

See this study on ClinicalTrials.gov

Testing Early Treatment for Patients With High-Risk Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL), EVOLVE CLL/SLL Study

Description:

This phase III trial compares early treatment with venetoclax and obinutuzumab versus delayed treatment with venetoclax and obinutuzumab in patients with newly diagnosed high-risk chronic lymphocytic leukemia or small lymphocytic lymphoma. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Immunotherapy with monoclonal antibodies, such as obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Starting treatment with the venetoclax and obinutuzumab early (before patients have symptoms) may have better outcomes for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma compared to starting treatment with the venetoclax and obinutuzumab after patients show symptoms.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Farrukh Awan

Gender: ALL

Age: 18 Years and over

Phase: PHASE3

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT04269902

IRB Number: STU-2022-0539

Show full eligibility criteria

Inclusion Criteria:

* Participants must have a confirmed diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (collectively referred to as CLL throughout) according to the 2018 International Workshop on CLL. Participants must have been diagnosed within 18 months prior to registration * Participants must have CLL-International Prognostic Index (CLL-IPI) score \>= 4 and/or complex cytogenetics (defined as 3+ chromosomal abnormalities) * Cytogenetic AND/OR FISH analyses must be completed at a Clinical Laboratory Improvement Act (CLIA)-approved (or laboratories accredited under Accreditation Canada Diagnostics to conduct FISH analyses) laboratory within 18 months prior to registration. At minimum, FISH panel should use probes to detect for abnormalities in chromosomes 13q, 12, 11q, and 17p * TP53 gene mutation analysis performed at any CLIA-approved (or laboratories accredited under Accreditation Canada Diagnostics) lab (if completed) must be obtained within 18 months prior to registration. This sequencing test is distinct from FISH studies for del(17p) * Note: TP53 gene mutation analysis is recommended but not required if the participant meets disease-related study criteria via a combination of risk factors that totals a score of 4 on the CLL-IPI score and/or has complex cytogenetics completed * Immunoglobulin heavy chain locus variable (IgVH) gene mutation analysis performed at any CLIA-approved lab (or laboratories accredited under Accreditation Canada Diagnostics) must be obtained prior to registration (at any time prior to registration) * Serum beta-2 microglobulin level must be obtained within 28 days prior to registration * Participants must not meet any of the IWCLL specified criteria for active CLL therapy * Treatment with high dose corticosteroids and/or intravenous immunoglobulin for autoimmune complications of CLL must be complete at least 4 weeks prior to enrollment * Steroids used for treatment of conditions other than CLL/SLL must be at a dose of at most 20 mg/day of prednisone or equivalent corticosteroid at the time of registration * Prior therapy with anti CD20 monoclonal antibodies is not allowed * Participants must not have received or be currently receiving any prior CLL-directed therapy, including non-protocol-related therapy, anti-cancer immunotherapy, experimental therapy (with exception of agents approved for emergency access use for the prevention or treatment of COVID-19), or radiotherapy * Participants must not be receiving or planning to receive any other investigational agents before completing protocol therapy * Participants must be \>= 18 years of age * Participants must have Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 * Platelet count \>= 100,000/mm\^3 within 28 days prior to registration * Absolute neutrophil count (ANC) \>= 1,000/mm\^3 within 28 days prior to registration * Creatinine clearance \>= 30mL/min (by Cockcroft Gault) within 28 days prior to registration * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3.0 x upper limit of normal (ULN) within 28 days prior to registration * Total bilirubin =\< 2.0 x ULN (or 5.0 x ULN if the participant has a history of Gilbert's disease), within 28 days prior to registration * Participants must be able to take oral medications * Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial * Participants with history of malignancy are allowed providing the cancer has not required active treatment within 2 years prior to registration (hormonal therapy is permissible). The following exceptions are permissible: basal cell, squamous cell skin, or non-melanomatous skin cancer, in situ cervical cancer, superficial bladder cancer not treated with intravesical chemotherapy or Bacillus Calmette-Guerin (BCG) within 6 months, localized prostate cancer requiring no more than chronic hormonal therapy, or localized breast cancer requiring no more than chronic hormonal therapy * Participants must not have current, clinically significant gastrointestinal malabsorption, in the opinion of treating doctor * Participants must not have cirrhosis * Obinutuzumab has been associated with hepatitis reactivation. Participants must not have uncontrolled active infection with hepatitis B or C. Participants with latent hepatitis B infection must agree to take prophylaxis during and for 6 months following active protocol therapy with V-O. * Active infection with hepatitis B or C: * Active infection is defined as detectable hepatitis B deoxyribonucleic acid (DNA) or hepatitis C ribonucleic acid (RNA) by quantitative polymerase chain reaction (PCR). * Latent infection with hepatitis B: * Latent infection is defined as meeting all of the following criteria: * Hepatitis B surface antigen positive * Anti-hepatitis B total core antibody positive * Anti-hepatitis IgM core antibody undetectable * Hepatitis B PCR undetectable * Participants with latent hepatitis B infection must agree to take prophylaxis with anti-hepatitis agents during and for 6 months following active protocol therapy with V-O. * Participants who have received intravenous immunoglobulin (IVIG) therapy within 6 months who are hepatitis B core total antibody positive but PCR undetectable are not mandated to take prophylaxis * Participants must not have had major surgery within 30 days prior registration or minor surgery within 7 days prior to registration. Examples of major surgery include neurosurgical procedures, joint replacements, and surgeries that occur inside the thoracic or abdomino-pelvic cavities. Examples of minor surgery include dental surgery, insertion of a venous access device, skin biopsy, or aspiration of a joint. If a participant has had a bone marrow biopsy for diagnosis or evaluation of CLL, this will not exclude the participant from registration to the study. If there is a question about whether a surgery is major or minor, this should be discussed with the Study Chair * Participants must not have known bleeding disorders (e.g., von Willebrand's disease or hemophilia) * Participants must not have a history of stroke or intracranial hemorrhage within 6 months prior to enrollment * Participants must not require continued therapy with a strong inhibitor or inducer of CYP3A4/5, as venetoclax is extensively metabolized by CYP3A4/5 * Participants must not have uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura * Participants must not have any currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification * Participants must not have a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to enrollment * Participants must not be pregnant or nursing, as there are no safety data available for these drug regimens during pregnancy. Women/men of reproductive potential must have agreed to use an effective contraceptive method. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 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, he/she is responsible for beginning contraceptive measures * Participants must agree to have specimens submitted for translational medicine (MRD) as outlined * Participants must be offered the opportunity to participate in specimen banking for future research as outlined. * NOTE: With participant's consent, the site must follow through with specimen submission as outlined * Participants who are able to complete patient reported outcome (PRO) forms in English, Spanish, French, German, Russian or Mandarin must agree to participate in the quality of life assessments. (Those participants who are unable to read and write in English, Spanish, French, German, Russian or Mandarin may be registered to S1925 without contributing to the quality of life portion of the study.) * Participants must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines * NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

Interventions: PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Computed Tomography, BIOLOGICAL: Obinutuzumab, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration, DRUG: Venetoclax

Conditions: Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

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

Description:

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.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Farrukh Awan

Gender: All

Age: 18 Years and over

Phase: Phase 1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT04137900

IRB Number: STU-2020-0419

Show full eligibility criteria

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.

Interventions: Drug: TAB004, Drug: Toripalimab

Conditions: Advanced Unresectable Solid Tumor, Metastatic Solid Tumor, Hodgkins Lymphoma, Lung/Thoracic, Lymphoma, Melanoma, skin, Non-Hodgkins Lymphoma, Lymphoid Leukemia

Keywords: immunotherapy, BTLA, HVEM, check point inhibitor, solid tumor, non-small cell lung cancer, NSCLC, melanoma, lymphoma, monoclonal antibody, phase 1 trial

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations

Description:

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.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Tanya Watt

Gender: ALL

Age: up to 25 Years old

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT04094610

IRB Number: STU-2019-1268

Show full eligibility criteria

Key

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 50.
• 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.

Interventions: DRUG: Oral repotrectinib (TPX-0005)

Conditions: Locally Advanced Solid Tumors, Metastatic Solid Tumors, Lymphoma, Primary CNS Tumors

Keywords: 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

Sites: Children’s Health

I'm interested

Share via email

See this study on ClinicalTrials.gov

A Clinical Trial of BP1002 in Patients With Advanced Lymphoid Malignancies

Description:

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.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Praveen Ramakrishnan Geethakumari

Gender: All

Age: 18 Years and over

Phase: Phase 1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT04072458

IRB Number: STU-2023-0236

Show full eligibility criteria

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.

Interventions: Drug: L-Bcl-2 antisense oligonucleotide

Conditions: Mantle Cell Lymphoma, Peripheral T-cell Lymphoma (PTCL), Cutaneous T-cell Lymphoma (CTCL), Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), Follicular Lymphoma, Marginal Zone Lymphoma, Hodgkin Lymphoma, Waldenström Macroglobulinemia, DLBCL, Hodgkins Lymphoma, Lymphoid Leukemia

Sites: UT Southwestern; Parkland Health & Hospital System

I'm interested

Share via email

See this study on ClinicalTrials.gov

Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy

Description:

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.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Tamra Slone

Gender: ALL

Age: 1 Year to 25 Years old

Phase: PHASE3

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT03959085

IRB Number: STU-2019-1574

Show full eligibility criteria

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.

Interventions: 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

Conditions: B Acute Lymphoblastic Leukemia, B Lymphoblastic Lymphoma, Central Nervous System Leukemia, Mixed Phenotype Acute Leukemia, Testicular Leukemia

Sites: Children’s Health

I'm interested

Share via email

See this study on ClinicalTrials.gov

Mevrometostat Treatment of Relapsed/Refractory SCLC, Castration Resistant Prostate Cancer, and Follicular Lymphoma

Description:

A Phase 1 Dose Escalation and Expanded Cohort Study Of PF-06821497 (Mevrometostat) in Adult Patients With Relapsed/Refractory Small Cell Lung Cancer (SCLC), Castration Resistant Prostate Cancer (CRPC) And Follicular Lymphoma (FL).

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Tian Zhang

Gender: ALL

Age: 18 Years and over

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT03460977

IRB Number: STU-2022-0733

Show full eligibility criteria

Key

Inclusion Criteria:

Histological or cytological diagnosis of advanced / metastatic solid tumor with the following tumor types in individual study parts: Part 1A (closed to enrollment): Part 1B (closed to enrollment): Part 1C: * Metastatic Castration resistant prostate cancer. Patients should have received either abiraterone and/or enzalutamide treatment and have evidence of prostate cancer progression (per PCWG3) Japan cohort * Castration resistant prostate cancer that is resistant to SOC or for which no local regulatory approved SOC is available that would confer significant clinical benefit in the medical judgement of the investigator. Patients should have received either abiraterone and/or enzalutamide treatment and have evidence of prostate cancer progression (per PCWG3) China cohort * Castration resistant prostate cancer that is intolerant/resistant to SOC or for which no local regulatory approved SOC is available that would confer significant clinical benefit in the medical judgement of the investigator. Patients who refused SOC may be eligible. Patients should have received either abiraterone and/or enzalutamide treatment and have evidence of prostate cancer progression (per PCWG3) Part 2A: • Metastatic Castration resistant prostate cancer. Patients should have received either abiraterone and/or enzalutamide treatment, may have received up to 1 line of chemotherapy and have evidence of prostate cancer progression (per PCWG3) Part 2B/2C: * Metastatic Castration resistant prostate cancer. Patients should have received abiraterone treatment, may have received up to 1 prior line of chemotherapy, have not received prior enzalutamide, apalutamide or darolutamide and have evidence of prostate cancer progression (per PCWG3) * Patients must have radiographic evidence of disease Other inclusion criteria: -Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1. Key

Exclusion Criteria:

• Prior Chemotherapy: Part 1C , Japan cohort and China cohort (CRPC): no more than 2 previous regimens of chemotherapy Part 2A: mCRPC: no more than 1 previous regimen of systemic chemotherapy Part 2B (mCRPC): no more than 1 previous regimen of chemotherapy * Prior irradiation to \>25% of the bone marrow. * QTcF interval \>480 msec at screening. * Hypertension that cannot be controlled by medications (\>150/90 mmHg despite optimal medical therapy). * Known or suspected hypersensitivity to PF 06821497 or any components or enzalutamide (CRPC) * Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease or previous gastric resection or lap band surgery. Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed. * Current use or anticipated need for food or drugs that are known strong CYP3A4/5 inducers or inhibitors, including their administration within 10 days or 5 half lives of the CYP3A4/5 inhibitor, whichever is longer prior to first dose of investigational product.

Interventions: DRUG: Mervometostat (PF-06821497), DRUG: Enzalutamide

Conditions: Metastatic Castration Resistant Prostate Cancer (mCRPC), Small Cell Lung Cancer (SCLC), Follicular Lymphoma (FL)

Keywords: EZH2, enhancer of zeste homolog 2, castrate resistant prostate cancer, prostatecancer-study.com, mCRPC, efficacy, safety, pharmacokinetics, pharmacodynamics, dose escalation, dose expansion, open-label, small cell lung cancer, SCLC, follicular lymphoma, FL, relapsed, refractory

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Participants with Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab or Rituximab and Chemotherapy (ALLELE)

Description:

The purpose of this study is to determine the clinical benefit and characterize the safety profile of tabelecleucel for the treatment of Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) in the setting of (1) solid organ transplant (SOT) after failure of rituximab and rituximab plus chemotherapy or (2) allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Tamra Slone

Gender: ALL

Age: Not specified

Phase: PHASE3

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT03394365

IRB Number: STU-2018-0349

Show full eligibility criteria

Inclusion Criteria:

• Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of these (C-SOT); or prior allogeneic HCT (C-HCT)
• A diagnosis of locally assessed, biopsy-proven EBV+ PTLD
• Availability of appropriate partially HLA-matched and restricted tabelecleucel has been confirmed by the sponsor
• Measurable, 18F-deoxyglucose (FDG)-avid (Deauville score ≥ 3) systemic disease using Lugano Classification response criteria by positron emission tomography (PET)-diagnostic computed tomography (CT), except when contraindicated or mandated by local practice, then magnetic resonance imaging (MRI) may be used. For subjects with treated central nervous system (CNS) disease, a head CT and/or brain/spinal MRI as clinically appropriate will be required to follow CNS disease response per Lugano Classification response criteria.
• Treatment failure of rituximab or interchangeable commercially available biosimilar monotherapy (C-SOT-R or C-HCT) or rituximab plus any concurrent or sequentially administered chemotherapy regimen (C-SOT-R+C) for treatment of PTLD.
• Males and females of any age.
• Eastern Cooperative Oncology Group performance status ≤ 3 for subjects aged ≥ 16 years; Lansky score ≥ 20 for subjects \< 16 years
• For C-HCT only: If allogeneic HCT was performed as treatment for an acute lymphoid or myeloid malignancy, the underlying primary disease for which the subject underwent transplant must be in morphologic remission
• Adequate organ function
• Absolute neutrophil count ≥ 1000/μL, (C-SOT) or ≥ 500/μL (C-HCT), with or without cytokine support
• Platelet count ≥ 50,000/μL, with or without transfusion or cytokine support. For C-HCT, platelet count \< 50,000/μL but ≥ 20,000/μL, with or without transfusion support, is permissible if the subject has not had grade ≥ 2 bleeding in the prior 4 weeks (where grading of the bleeding is determined per the National Cancer Institute's Common Terminology Criteria for Adverse Events \[CTCAE\], version 5.0)
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin each \< 5 × the upper limit of normal; however, ALT, AST, and total bilirubin each ≤ 10 × upper limit of normal is acceptable if the elevation is considered by the investigator to be due to EBV and/or PTLD involvement of the liver as long as there is no known evidence of significant liver dysfunction
• Subject or subject's representative is willing and able to provide written informed consent

Exclusion Criteria:

• Burkitt lymphoma, classical Hodgkin lymphoma, or any T cell lymphoma
• Daily steroids of \> 0.5 mg/kg prednisone or glucocorticoid equivalent, ongoing methotrexate, or extracorporeal photopheresis
• Untreated CNS PTLD or CNS PTLD for which the subject is actively receiving CNS-directed chemotherapy (systemic or intrathecal) or radiotherapy at enrollment. NOTE:Subjects with previously treated CNS PTLD may enroll if CNS-directed therapy is complete.
• Suspected or confirmed grade ≥ 2 graft-versus-host disease (GvHD) per the Center for International Blood and Marrow Transplant Research consensus grading system at enrollment
• Ongoing or recent use of a checkpoint inhibitor agent (eg, ipilimumab, pembrolizumab, nivolumab) within 3 drug half-lives from the most recent dose to enrollment
• For C-HCT: active adenovirus viremia
• Need for vasopressor or ventilatory support
• Antithymocyte globulin or similar anti-T cell antibody therapy ≤ 4 weeks prior to enrollment
• Treatment with Epstein-Barr virus cytotoxic T lymphocytes or chimeric antigen receptor T cells directed against B cells within 8 weeks of enrollment (C-SOT or C-HCT), or unselected donor lymphocyte infusion within 8 weeks of enrollment (C-HCT only)
• Female who is breastfeeding or pregnant or female of childbearing potential or male with a female partner of childbearing potential unwilling to use a highly effective method of contraception
• Inability to comply with study-related procedures
• Any medical condition or organ system dysfunction that in the investigator\'s opinion, could compromise the participant\'s safety or ability to complete the study

Interventions: BIOLOGICAL: tabelecleucel

Conditions: Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Solid Organ Transplant Complications, Lymphoproliferative Disorders, Allogeneic Hematopoietic Cell Transplant, Stem Cell Transplant Complications

Keywords: Epstein-Barr Virus (EBV)-associated Lymphoproliferative Disease (LPD), Epstein-Barr Virus (EBV), Cytotoxic T lymphocyte (CTL), Cancer After Transplant, Kidney transplant, Renal transplant, Liver transplant, Heart transplant, Lung transplant, Intestinal transplant, Pancreas transplant, Post-transplant Lymphoma, Solid Organ Transplant (SOT), Bone Marrow Transplant Complications, Epstein-Barr Virus-specific Cytotoxic T Lymphocytes (EBV-CTL), Hematopoietic Cell Transplant (HCT), Hematopoietic Stem Cell Transplantation (HSCT), Allogeneic Hematopoietic Cell Transplant, Allogeneic, Off-The-Shelf T-cell Immunotherapy

Sites: Children’s Health

I'm interested

Share via email

See this study on ClinicalTrials.gov

Study Evaluating Safety and Efficacy of JCAR017 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)

Description:

This is a Phase 1/2, open-label, multicenter study to determine the efficacy and safety of JCAR017 in adult subjects with relapsed or refractory CLL or SLL. The study will include a Phase 1 part to determine the recommended dose of JCAR017 monotherapy in subjects with relapsed or refractory CLL or SLL, followed by a Phase 2 part to further assess the efficacy and safety of JCAR017 monotherapy treatment at the recommended dose. A separate Phase 1 cohort will assess the combination of JCAR017 and concurrent ibrutinib. Another separate Phase 1 cohort will assess the combination of JCAR017 and concurrent venetoclax. In all subjects, the safety, efficacy, and pharmacokinetics (PK) of JCAR017 will be evaluated.

Contact(s):

Call 833-722-6237
canceranswerline@utsouthwestern.edu

Principal Investigator: Farrukh Awan

Gender: ALL

Age: 18 Years and over

Phase: PHASE1

Healthy Volunteers:

This study is NOT accepting healthy volunteers

System ID: NCT03331198

IRB Number: STU-2019-0562

Show full eligibility criteria

Inclusion Criteria:

* Diagnosis of:
• CLL with an indication for treatment based on the Investigator's opinion and measurable disease, or
• SLL (lymphadenopathy and/or splenomegaly and \< 5×10\^9 CD19+ CD5+ clonal B lymphocytes/L \[\< 5000/µL\] in the peripheral blood at diagnosis with measurable disease that is biopsy-proven SLL) * Subjects (other than those in the ibrutinib + JCAR017 combination therapy and DEME cohort) must have received and failed Bruton tyrosine kinase inhibitor (BTKi) treatment or have been deemed ineligible for BTKi therapy. * Subjects in the JCAR017 monotherapy cohorts must have received previous treatment as follows:
• Monotherapy cohorts EXCEPT DEME cohort: Subjects with CLL or SLL and high-risk features must have failed at least 2 lines of prior therapy.
• Monotherapy cohorts EXCEPT DEME cohort: Subjects with CLL or SLL and standard-risk features must have failed at least 3 lines of prior therapy.
• DEME cohort ONLY: Subjects with relapsed or refractory CLL or SLL, irrespective of cytogenetic risk features, must have received at least 2 lines of prior therapy including a BTKi and a BCL2i. * Subjects in the ibrutinib + JCAR017 combination therapy cohort must either:
• be receiving ibrutinib and progressing at the time of study enrollment
• be receiving ibrutinib for at least 6 months with a response less than complete response/remission (CR) and have high-risk features as defined in inclusion criterion 5a
• have BTK or PLCgamma2 mutations per local laboratory assessment, with or without progression on ibrutinib
• have previously received ibrutinib and have no contraindications to restarting ibrutinib * Eastern Cooperative Oncology Group performance status of ≤ 1 * Assessed by the Investigator to have adequate bone marrow function to receive lymphodepleting chemotherapy * Adequate organ function, defined as:
• Serum creatinine ≤ 1.5 × age-adjusted upper limit of normal (ULN) OR calculated creatinine clearance \> 30 mL/min
• Alanine aminotransferase ≤ 5 × ULN and total bilirubin \< 2.0 mg/dL (or \< 3.0 mg/dL for subjects with Gilbert's syndrome or leukemic infiltration of the liver)
• Adequate pulmonary function, defined as ≤ Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 dyspnea and saturated oxygen (SaO2) ≥ 92% on room air
• Adequate cardiac function, defined as left ventricular ejection fraction ≥ 40% as assessed by echocardiogram or multiple uptake gated acquisition scan performed within 30 days prior to determination of eligibility * Subject either currently has central vascular access or is a candidate to receive central vascular access or peripheral vascular access for leukapheresis procedure. * If prior CD19-targeted therapy has been administered, subject must have CD19-positive disease confirmed by immunohistochemistry or flow cytometry since completing the prior CD19-targeted therapy. * Subjects in ibrutinib + JCAR017 combination cohort must have progressed on a BTKi and have received prior therapy with venetoclax * Subjects in venetoclax + JCAR017 combination cohort must:
• have failed at least 1 prior line of therapy, including failed BTKi therapy or have been deemed ineligible to receive BTKi
• be venetoclax naive (required for dose expansion) or
• if prior venetoclax (only for dose escalation)
• have no contraindictions to re-initiation of venetoclax based on prior intolerance and have had at least 6 months elapsed since the last dose of venetoclax, if either, best response was stable disease, or subject experienced disease progression on venetoclax, or within 6 months of venetoclax discontinuation * subjects in the venetoclax + JCAR017 combination must have hemoglobin \>=9 g/dL, absolute neutrophil count \>=500mm3 and platelets\>= 75,000/mm3, unless cytopenias are judged by investigator to be due to CLL infiltration of the bone marrow * must have diagnosis of CLL or SLL with an indication for treatment based on the investigator's opinion and measurable disease (any of the following measurable lymph nodes ≥1.5 cm in the greatest transverse diameter and/or hepatomegaly or splenomegaly) and demonstration of CLL cells in the peripheral blood by flow cytometry

Exclusion Criteria:

* Subjects with known active central nervous system (CNS) involvement by malignancy. Those with prior CNS disease that has been effectively treated will be eligible if treatment was completed at least 3 months prior to enrollment with no evidence of symptomatic disease and stable abnormalities on repeat imaging. * History of another primary malignancy that has not been in remission for at least 2 years. (The following are exempt from the 2-year limit: nonmelanoma skin cancer, completely resected stage 1 solid tumor with low risk for recurrence, curatively treated localized prostate cancer, cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Pap smear, and in situ breast cancer that has been completely resected.) * Subjects with Richter's transformation * Prior treatment with any gene therapy product * Active hepatitis B, active hepatitis C, or active human immunodeficiency virus (HIV) infection * Systemic fungal, bacterial, viral, or other infection that is not controlled * Presence of acute or extensive chronic graft versus host disease (GVHD) * History of any one of the following cardiovascular conditions within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease * History or presence of clinically relevant CNS pathology such as epilepsy, generalized seizure disorder, aphasia, stroke with current neurologic sequelae, severe brain injuries, dementia, Parkinson's disease, cerebellar disease,cerebral edema, or psychosis * Pregnant or nursing (lactating) women * Use of any of the following medications or treatments within the noted time prior to leukapheresis:
• Alemtuzumab within 6 months prior to leukapheresis
• Allogeneic hematopoietic stem cell transplant within 100 days prior to leukapheresis
• Cladribine within 3 months prior to leukapheresis
• Donor lymphocyte infusions (DLI) within 2 months prior to leukapheresis
• Radiation including large bone marrow fields such as sternum or pelvis within 6 weeks prior to leukapheresis
• Fludarabine within 4 weeks prior to leukapheresis
• GVHD therapies such as calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolate mofetil, rapamycin, or immunosuppressive antibodies (such as anti-tumor necrosis factor-α \[TNFα\], anti-interleukin-6 \[IL-6\], or anti-interleukin-6 receptor \[IL 6R\]) within 4 weeks prior to leukapheresis
• Cyclophosphamide, ifosfamide, bendamustine, chlorambucil, or melphalan within 2 weeks prior to leukapheresis
• Therapeutic doses of corticosteroids (defined as \> 20 mg/day prednisone or equivalent) within 7 days prior to leukapheresis
• Anti-CD20 monoclonal antibodies within 7 days prior to leukapheresis
• Venetoclax within 4 days prior to leukapheresis
• Idelalisib or duvelisib within 2 days prior to leukapheresis
• Lenalidomide or covalent and non-covalent BTKi within 1 day prior to leukapheresis
• Experimental agents, including off-label use of approved drugs (with the exception of acalabrutinib which may be continued up to the day before leukapheresis), within 4 weeks prior to leukapheresis unless progression is documented on the experimental therapy and at least 3 half-lives have elapsed prior to leukapheresis * Uncontrolled medical, psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol, as judged by the Investigator; or subject unwillingness or inability to follow the procedures required in the protocol * Progressive vascular tumor invasion, thrombosis, or embolism * Deep vein thrombosis or embolism not managed on a stable regimen of anticoagulation * Use of any of the following medications or treatments within the noted time prior to leukapheresis lenalidomide or acalabrutinib within 1 day prior to leukapheresis experimental agents, including off-label use of approved drugs, within 4 weeks prior to leukapheresis. * Venous thrombosis or embolism requiring treatment but not managed on a stable regimen of anticoagulation * For subjects in the venetoclax + JCAR017 combination cohorts only, concomitant treatment with CYP3A moderate/strong inducers or moderate/strong inhibitors which cannot be discontinued

Interventions: BIOLOGICAL: JCAR017 (lisocabtagene maraleucel), BIOLOGICAL: JCAR017 (lisocabtagene maraleucel) + ibrutinib, BIOLOGICAL: JCAR017 (lisocabtagene maraleucel) + venetoclax

Conditions: Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Small Lymphocytic

Keywords: TRANSCEND_CLL_004

Sites: UT Southwestern

I'm interested

Share via email

See this study on ClinicalTrials.gov

Search Results

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 2 Study of Firi-cel in Patients With Relapsed/Refractory Large B-cell Lymphoma (FIRCE-1)

A Safety and Efficacy Study of HCB101, Fc-fusion Protein Targeting SIRPα-CD47 Pathway, in Solid or Hematological Tumors

A Study of AC676 for the Treatment of Relapsed/Refractory B-Cell Malignancies

A Study to Compare Standard Therapy to Treat Hodgkin Lymphoma to the Use of Two Drugs, Brentuximab Vedotin and Nivolumab

A Trial to Study if REGN5837 in Combination With Odronextamab is Safe for Participants With Aggressive B-cell Non-Hodgkin Lymphomas (ATHENA-1)

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)

Study of SGR-1505 in Mature B-Cell Neoplasms

A Study to Evaluate Adverse Events of Subcutaneous (SC) Epcoritamab Administered in the Outpatient Setting in Adult Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma and Classic Follicular Lymphoma

A Study of CNTY-101 in Participants With CD19-Positive B-Cell Malignancies (ELiPSE-1)

Study of the Adverse Events and Change in Disease State of Pediatric Participants (and Young Adults Between the Ages of 18-25) With Relapsed/Refractory Aggressive Mature B-cell Neoplasms Receiving Subcutaneous (SC) Injections of Epcoritamab

Study of ONO-4685 in Patients With Relapsed or Refractory T Cell Lymphoma

An Open-Label, Phase 2 Trial of Nanatinostat in Combination With Valganciclovir in Patients With Epstein-Barr Virus-Positive (EBV+) Relapsed/Refractory Lymphomas (NAVAL-1)

CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma

DALY II USA/ MB-CART2019.1 for DLBCL

Nivolumab in Combination With Chemo-Immunotherapy for the Treatment of Newly Diagnosed Primary Mediastinal B-Cell Lymphoma

Efficacy and Safety of Nemtabrutinib (MK-1026) in Participants With Hematologic Malignancies (MK-1026-003)

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

Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome (EPCORE™ CLL-1)

Testing the Addition of Lenalidomide and Nivolumab to the Usual Treatment for Primary CNS Lymphoma

Safety and Efficacy Trial of Epcoritamab Combinations in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL) (EPCORE™ NHL-2)

A Study of Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP) with or Without Selinexor in Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma

Testing Early Treatment for Patients With High-Risk Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL), EVOLVE CLL/SLL Study

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

A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations

A Clinical Trial of BP1002 in Patients With Advanced Lymphoid Malignancies

Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy

Mevrometostat Treatment of Relapsed/Refractory SCLC, Castration Resistant Prostate Cancer, and Follicular Lymphoma

Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Participants with Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab or Rituximab and Chemotherapy (ALLELE)

Study Evaluating Safety and Efficacy of JCAR017 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)

Email this study information to me

Contact the study team