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APVO436 Phase 1b/2 Study in Patients With Newly Diagnosed AML
A multi-center, open-label, dose-finding study of five dose levels of APVO436 in combination with venetoclax and azacitidine (ven/aza) in adult patients with newly diagnosed, CD123+ AML.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years to old
PHASE1
NCT06634394
STU-2024-1192
Inclusion Criteria:
* 1. Age ≥18 years. 2. Patient must have confirmation of AML based on 2016 World Health Organization (WHO) criteria and not been previously treated.
• Patients must have CD123-positive AML as confirmed by local flow cytometry (or immunohistochemistry \[IHC\]). Confirmation at diagnosis is acceptable.
• Patient must be considered ineligible for induction therapy defined by at least one of the following:
• ≥75 years of age
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or 3
• Cardiac disorder (e.g., congestive heart failure requiring treatment, ejection fraction ≤ 50%, or chronic stable angina)
• Pulmonary disorder (e.g., DLCO ≤65% or FEV1 ≤65%)
• Creatinine clearance 30-45 mL/min based on Cockcroft-Gault or Modified of Diet in Renal Disease (MDRD) formular
• Hepatic disorder with total bilirubin between 1.5 and 3 times the ULN 5. Patient must have a projected life expectancy of ≥12 weeks
Exclusion Criteria:
• Patient has received treatment with the following:
• A hypomethylating agent, venetoclax, and/or chemotherapeutic agent for AML, myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), or myelodysplastic/myeloproliferative neoplasms (MPS/MPN)
• CAR-T cell therapy or history of allogeneic hematopoietic stem cell transplant (HSCT)
• Experimental therapies for MDS or AML
• Patient is currently participating in another interventional research study.
• Patient has history of MPN including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia (CML) with or without BCR-ABL1 translocation, or AML with BCR-ABL1 translocation.
• Patient has acute promyelocytic leukemia.
• Patient has a current autoimmune disorder requiring immunosuppressive therapy such as systemic (oral or IV) steroid therapy \>10 mg methylprednisolone daily or its equivalent
• Patient is receiving concurrent corticosteroid therapy as an anticancer drug (any dose).
• Patient has known active CNS involvement with AML. Patients who received intrathecal chemotherapy for prophylaxis of AML in the CNS prior to enrollment may enroll in this study.
• Creatinine clearance \<30ml/min based on Cockcroft-Gault or MDRD formular.
• Bilirubin of \>3xULN in the absence of Gilbert's Syndrome.
• AST and/or ALT \>3 times the ULN.
DRUG: APVO436, DRUG: Venetoclax, DRUG: Azacitidine
Acute Myeloid Leukemia (AML), Myeloid and Monocytic Leukemia
Acute Myeloid Leukemia
UT Southwestern
Ivosidenib (IVO) Monotherapy and Azacitidine (AZA) Monotherapy in Patients With Hypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS) With an IDH1 Mutation (PyramIDH)
This study will enroll participants with myelodysplastic syndromes (MDS) with an Isocitrate dehydrogenase protein, 1 (IDH1) mutation, who have not received treatment with a hypomethylating agent previously. Participants will be randomized to receive either ivosidenib (IVO) alone or azacitidine (AZA) alone. IVO will be administered daily throughout the 28-day treatment cycle and AZA will be administered for the first 7 days of each 28-day cycle. Study visits will be conducted every week during Cycle 1 (Days 1, 8, 15, and 22), and Day 1 of each cycle thereafter. After the last dose of treatment, participants will attend an safety follow-up visit and participants will be followed to assess overall survival. Study visits may include a bone marrow aspirate, physical exam, echocardiogram (ECHO), electrocardiogram (ECG), blood and urine analysis, and questionnaires.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years to old
PHASE3
NCT06465953
STU20251131
Inclusion Criteria:
* Diagnosis of HMA naive IDH1 R132 mutated MDS defined according to WHO criteria (5th edition):
* Moderate high, high and very high-risk MDS per IPSS-M score will be eligible regardless of blood counts and with blast counts 0-19%.
* Low and moderate low-risk MDS per IPSS-M score must:
* Have cytopenias related to MDS, defined as: \<100 platelets/microliter, or absolute neutrophil count (ANC) \<1000/mm3, or hemoglobin \<10g/dL AND
* Have a blast count between 5-19% AND
* Be eligible for HMA therapy (very low risk participants are to be excluded)
* Locally or centrally confirmed IDH1 R132 C/G/H/L/S mutation
Exclusion Criteria:
* Received prior anticancer/disease modifying treatment for MDS (including HMA's, cytotoxic chemotherapy, investigational agents, bcl-2 inhibitor based-regimens, hematopoietic stem cell transplant (HSCT), IDH1 inhibitors). For LR-MDS patients, prior treatment with growth factors, luspatercept, lenalidomide, and imetelstat are allowed.
* \>20% blasts by morphology or immunohistochemistry on screening bone marrow aspirate/biopsy DRUG: Ivosidenib, DRUG: Azacitidine
Hypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS), Myelodysplastic Syndromes (MDS)
UT Southwestern
A Study to Investigate the Safety and Tolerability of Ziftomenib in Combination With Venetoclax/Azacitidine, Venetoclax, 7+3, or 7+3+Quizartinib in Patients With AML
Ziftomenib is an investigational drug in development for the treatment of patients with acute myeloid leukemia (AML) with certain genetic alterations. This protocol has 3 separate arms that will investigate the benefits and risks of adding ziftomenib to standard-of-care (SOC) drug treatments in patients who have AML with certain genetic mutations. Both newly diagnosed and relapsed refractory patients with AML will be assigned to different cohorts based on specific study criteria and physician discretion. The purpose of this study is to assess the safety, tolerability, and early signs of efficacy of ziftomenib in combination with SOC drugs to treat AML.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years and over
PHASE1
NCT05735184
STU-2023-0858
Key
Inclusion Criteria:
* Patients must have a documented NPM1 mutation or KMT2A rearrangement and have either newly diagnosed or relapsed/refractory AML
* Those intending treatment with intensive chemotherapy in Arm C should be NPM1-m and FLT3-ITD+ with an allelic ratio ≥0.05 and eligible for FLT3-targeted treatment
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
* Adequate liver, renal, and cardiac function according to protocol defined criteria
* A female of childbearing potential must agree to use adequate contraception as well as a double barrier method from the time of screening through 180 days following the last dose of study intervention. A male of childbearing potential must agree to use abstinence or use a double barrier method of contraception from the time of screening through 180 days following the last dose of study intervention
* Female patients of childbearing potential who receive quizartinib in Arm C should use a highly effective method of contraception during quizartinib treatment and for 7 months after the last dose
Key Exclusion Criteria:
* Diagnosis of either acute promyelocytic leukemia or blast phase chronic myeloid leukemia
* Known history of BCR-ABL alteration
* Advanced malignant hepatic tumor
* Administration of live attenuated vaccines within 14 days prior to, during, or after treatment until B-cell recovery
* Active central nervous system (CNS) involvement by AML.
* Clinical signs/symptoms of leukostasis or WBC \> 25,000 / microliter. Hydroxyurea and/or leukapheresis and/or up to 2 doses of cytarabine if used per institutional SOC for control of leukocytosis are permitted to meet this criterion
* Not recovered to Grade ≤1 (NCI-CTCAE v5.0) from all nonhematological toxicities except for alopecia
* Known clinically active human immunodeficiency virus, active hepatitis B or active hepatitis C infection
* For newly diagnosed cohorts: received prior chemotherapy for leukemia, except hydroxyurea and/or leukapheresis and/or up to 2 doses of cytarabine per institutional standards to control leukocytosis, or prior treatment with all-transretinoic acid for initially suspected acute promyelocytic leukemia
* For relapsed/refractory cohorts: received chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy that is considered to be investigational \< 14 days prior to the first dose of ziftomenib or within 5 drug half-lives prior to the first dose of study drug
* Uncontrolled intercurrent illness including, but not limited to, cardiac illness as defined in the protocol
* Mean QT interval corrected for heart rate by Fredericia's formula (QTcF)
* Arm A and Arm B: \>480 ms on triplicate ECGs
* Arm C: \>450 ms on triplicate ECGs
* Uncontrolled infection
* Women who are pregnant or lactating
* An active malignancy and currently receiving chemotherapy for that malignancy or disease that is uncontrolled/progressing
* Patients who have active GVHD requiring \>0.5 mg/kg prednisone or any new or increase in immunosuppressants in the prior 2 weeks for GVHD treatment DRUG: Ziftomenib, DRUG: Venetoclax, DRUG: Azacitidine, DRUG: Daunorubicin, DRUG: Cytarabine, DRUG: Quizartinib
Acute Myeloid Leukemia, Mixed Lineage Leukemia Gene Mutation, Refractory AML, AML With Mutated NPM1, Acute Myeloid Leukemia Recurrent, Acute Myeloid Leukemia, in Relapse, NPM1 Mutation, KMT2Ar, Myeloid Sarcoma, Nucleophosmin 1-mutated Acute Myeloid Leukemia, Myeloid and Monocytic Leukemia
Leukemia, Myeloid, AML, Hematological malignancy, KMT2A, NPM1, Menin, Acute Leukemia, Newly diagnosed AML, Untreated AML, venetoclax, cytarabine, daunorubicin, KMT2A-r, NPM1 mutation, Refractory AML, Acute Myeloid Leukemia, in Relapse, quizartinib
UT Southwestern
Canakinumab for the Prevention of Progression to Cancer in Patients With Clonal Cytopenias of Unknown Significance, IMPACT Study
This phase II trial tests how well canakinumab works to prevent progression to cancer in patients with clonal cytopenias of unknown significance (CCUS). CCUS is a blood condition defined by a decrease in blood cells. Blood cells are composed of either red blood cells, white blood cells, or platelets. In patients with CCUS, blood counts have been low for a long period of time. Patients with CCUS also have a mutation in one of the genes that are responsible for helping blood cells develop. The combination of genetic mutations and low blood cell counts puts patients with CCUS at a higher risk to develop blood cancers in the future. This transformation from low blood cell counts to cancer may be caused by inflammation in the body. Canakinumab is a monoclonal antibody that may block inflammation in the body by targeting a specific antibody called the anti-human interleukin-1beta (IL-1beta).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years to old
PHASE2
NCT05641831
STU-2024-0699
Inclusion Criteria:
* Patients with age \>= 18 with high-risk CCUS
* Must meet ALL the following criteria:
* Unexplained, clinically meaningful cytopenias (greater than 4 months) in one or more of the following lineages: erythroid cells, neutrophils, platelets. Clinically meaningful cytopenia is institution specific and threshold may vary on age, sex, and race. Decision-making should depend upon lab values specific to the institution and supersede public works. Based upon published work, significant cytopenias are defined as the following (must meet criteria in at least one lineage):
* Erythroid Cells:
* Hemoglobin \< 11 g/dL
* White Blood Cells:
* Absolute Neutrophil Count \< 1800/microL and \> 500/microL
* Platelets:
* Platelet Count \< 150,000/microL and \> 50,000/microL
* MDS criteria not fulfilled
* No other evidence of hematological malignancy
* No or only mild (\< 10%) bone marrow dysplasia
* Blast cells \< 5% detected via morphologic examination of blood and/or bone marrow smears which can also be supported by flow cytometry and/or immunohistochemical studies
* Any of the following:
* Isolated somatic spliceosome mutation at any VAF (SRSF2, SF3B1, U2AF1, or ZRSR2)
* Isolated TP53 mutation greater than 5% VAF
* At least 1 mutation in TET2, DMNT3A, or ASXL1 at any VAF coupled with at least 1 other known myeloid pathogenic somatic mutation or known pathogenic germline mutation that predisposes to myeloid malignancy as determined by next generation sequencing and bone marrow biopsy
* A TET2, DMNT3A, or ASXL1 greater than 10% VAF coupled with another TET2, DMNT3A, or ASXL1 greater than 10% VAF
* The presence of two or more known myeloid pathogenic somatic or germline mutations (other than TET2, ASXL1, DMNT3A, TP53, or spliceosome mutations) greater than 10% VAF
* Ability to understand and willingness to sign the written informed consent document
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
* Patients with a history of hypertension or active hypertension are strongly encouraged to optimize blood pressure control
* Creatinine clearance greater than 45 ml/min using Cockcroft-Gault
* Total bilirubin =\< 1.5 x ULN
* Aspartate transaminase (AST) \< 3 x ULN
* Alanine transaminase (ALT) \< 3 x ULN
Exclusion Criteria:
* Concurrent malignancy requiring active systemic therapy
* Diagnosis of MDS or any other myeloid malignancy in the patient's lifetime
* History of Hypersensitivity to canakinumab or drug of a similar class
* Active infection requiring prompt evaluation and treatment or history of recurrent infections
* Known active or recurrent hepatic disorder including cirrhosis, hepatitis B and C (via positive or indeterminate central laboratory \[lab\] results)
* Subjects with active tuberculosis. In subjects with a history of tuberculosis but without active tuberculosis, if the results of the evaluation require treatment per local guidelines, then the treatment should be initiated before randomization (unless otherwise required by Health Authorities or Institutional Review Board (IRB) in which case curative treatment must be completed prior to screening)
* Subjects with suspected or proven immunocompromised state or infections. If the results of this screening per local treatment guidelines or clinical practice require treatment for said infection then the patient is not eligible. Suspected or proven immunocompromised states or infections include:
* Those with any other medical condition such as active infection, treated or untreated, which in the opinion of the investigator places the subject at an unacceptable risk for participation in immunomodulatory therapy. If in the opinion of the investigator, the patient's immunocompromised state does not pose an unacceptable risk for participation, in the absence of uncontrolled infection, and the patient does not have a history of serious infections (such as tuberculosis); then the patient may participate in this study.
* Known history of testing positive for human immunodeficiency virus (HIV) infections. For countries where HIV status is mandatory: testing positive for HIV during screening using a local test.
* Allogeneic bone marrow or solid organ transplant (history of any or within a certain period of time?)
* Those requiring systemic or local treatment in doses with systemic effects e.g.:
* Prednisone \> 20 mg (or equivalent) oral or intravenous daily for \> 14 days
* Prednisone \> 5 mg and =\< 20 mg (or equivalent) daily for \> 30 days
* Equivalent dose of methotrexate \> 15 mg weekly
* Note: Azathioprine is allowed. Daily glucocorticoid-replacement for conditions such as adrenal or pituitary insufficiency is allowed. Topical, inhaled or local steroid use in doses that are not considered to cause systemic effects are permitted. Steroids for pre-medication related to chemotherapy as per local standard of care are permitted.
* Live or attenuated vaccination within 3 months prior to first dose of study drug (e.g. Measles/Mumps/Rubella \[MMR\], Yellow Fever, Rotavirus, Smallpox, etc.) and after initiation of canakinumab treatment
* Use of erythropoietin stimulating agents (ESA) or growth factors within four weeks prior to the start of the study
* Pregnant or nursing women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using basic methods of contraception during dosing of study treatment and for up to 130 days after last dose of study drug. Basic contraception methods include:
* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least 6 weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
* Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject
* Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps). For UK: with spermicidal foam/gel/film/cream/ vaginal suppository
* Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate \< 1%), for example hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS). In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Prior to entry into this study, cisplatin-based chemotherapy, which may be toxic to the fetus, may be given. The time between the end of cisplatin-based chemotherapy and the start canakinumab/placebo treatment is variable, resulting in a variable need for continuation of highly effective contraception. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (i.e. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks prior to first dose of study drug. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the Informed Consent Form (ICF). PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration and Biopsy, DRUG: Canakinumab, PROCEDURE: Chest Radiography, PROCEDURE: Echocardiography, DRUG: Placebo Administration, OTHER: Quality-of-Life Assessment
Clonal Cytopenia of Undetermined Significance, Myeloid and Monocytic Leukemia, Leukemia, Not Otherwise Specified, Leukemia, Other
UT Southwestern
Pemigatinib After Chemotherapy for the Treatment of Newly Diagnosed Acute Myeloid Leukemia
This phase I trial identifies the best dose and clinical benefit of giving pemigatinib following standard induction chemotherapy in patients with newly diagnosed acute myeloid leukemia. Pemigatinib selectively inhibits FGFR (fibroblast growth factor receptor) activity, a receptor that may contribute to the growth of leukemia cells. The genetic changes responsible for activating the growth of leukemia cells can be unique to each patient and can change during the course of the disease. Chemotherapy drugs, such as cytarabine and daunorubicin 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.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years to old
PHASE1
NCT04659616
STU-2023-0606
Inclusion Criteria:
* PRE-SCREENING INCLUSION CRITERIA: Ability to understand and the willingness to sign a written informed consent document
* PRE-SCREENING INCLUSION CRITERIA: Age \>= 18 years at time of informed consent. Both men and women of all races and ethnic groups will be included
* PRE-SCREENING INCLUSION CRITERIA: Participants must consent to a bone marrow aspirate/biopsy that will be collected prior to start of planned 7+3 induction therapy. Patients with known favorable risk AML (2022 European Leukemia Net \[ELN\] Guidelines) or FLT3 mutations should not be pre-screened. If the risk category is unknown, then it is okay to pre-screen patients for study. Adverse or intermediate risk needs to be confirmed prior to treatment with pemigatinib (during screening period) as outlined below
* TREATMENT INCLUSION CRITERIA: Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* TREATMENT INCLUSION CRITERIA: For both the dose-determining and dose-expansion cohort, study population is limited to: Newly diagnosed, morphologically documented AML, based on the World Health Organization (WHO) 2008 classification, with wild-type FLT3 and cytogenetics or mutations associated with intermediate or adverse prognostic risk per European Leukemia Net (ELN) guidelines. These include:
* t(9;11)(p21.3;q23.3); MLLT3-KMT2A
* Cytogenetic abnormalities not classified as favorable
* t(6;9)(p23;q34.1); DEK-NUP214
* t(v;11q23.3); KMT2A rearranged
* t(9;22)(q34.1;q11.2); BCR-ABL1
* inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2,MECOM(EVI1)
* -5 or del(5q); -7; -17/abn(17p)
* Complex karyotype - defined as three or more unrelated chromosome abnormalities in the absence of 1 of the WHO-designated recurring translocations or inversions, that is, t(8;21), inv(16) or t(16;16), t(9;11), t(v;11)(v;q23.3), t(6;9), inv(3) or t(3;3); AML with BCR-ABL1
* Monosomal karyotype - defined by the presence of 1 single monosomy (excluding loss of X or Y) in association with at least 1 additional monosomy or structural chromosome abnormality (excluding core-binding factor AML)
* Mutated RUNX1 (without favorable risk cytogenetics/mutations)
* Mutated BCOR (without favorable risk cytogenetics/mutations)
* Mutated EZH2 (without favorable risk cytogenetics/mutations)
* Mutated ASXL1 (without favorable risk cytogenetics/mutations)
* Mutated SF3B1 (without favorable risk cytogenetics/mutations)
* Mutated SRSF2 (without favorable risk cytogenetics/mutations)
* Mutated STAG2 (without favorable risk cytogenetics/mutations)
* Mutated U2AF1, (without favorable risk cytogenetics/mutations)
* Mutated ZRSR2 (without favorable risk cytogenetics/mutations)
* Mutated TP53 (mono- or biallelic) at a variant allele fraction of at least 10%
* TREATMENT INCLUSION CRITERIA: Serum creatinine clearance \>= 30 mL/min (as calculated by Cockcroft-Gault formula) (on or by day 8 of induction therapy, prior to starting pemigatinib)
* TREATMENT INCLUSION CRITERIA: Serum phosphate within institutional upper limit of normal (ULN) or can be corrected with supplementation/ phosphate binders to be within institutional ULN (on or by day 8 of induction therapy, prior to starting pemigatinib)
* TREATMENT INCLUSION CRITERIA: Serum electrolytes within institutional ULN: potassium, calcium (total, or corrected for serum albumin in case of hypoalbuminemia) and magnesium. If outside of normal limits, participant will be eligible when electrolytes are corrected (on or by day 8 of induction therapy, prior to starting pemigatinib)
* TREATMENT INCLUSION CRITERIA: Total serum bilirubin =\< 3 x ULN (on or by day 8 of induction therapy, prior to starting pemigatinib)
* TREATMENT INCLUSION CRITERIA: Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) =\< 3 x ULN (on or by day 8 of induction therapy, prior to starting pemigatinib)
* TREATMENT INCLUSION CRITERIA: Participants must consent to standard of care bone marrow aspirate/biopsies during treatment. Bone marrow biopsies will be obtained prior to study, on day 21 (+/- 3 days, if considered institutional standard of care), after recovery from induction therapy, and at the end of consolidation and/or prior to allogeneic stem cell transplant
* TREATMENT INCLUSION CRITERIA: Female participants of childbearing potential must agree to use effective contraception (2 forms of contraception or abstinence) from the screening visit until 6 months following the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
* TREATMENT INCLUSION CRITERIA: Male patients of childbearing potential having intercourse with females of childbearing potential must agree to abstain from heterosexual intercourse or have their partner use 2 forms of contraception from the screening visit until 3 months following the last dose of study treatment. The male participant must also refrain from sperm donation from the screening visit until 3 months following the last dose of study treatment
Exclusion Criteria:
* PRE-SCREENING EXCLUSION CRITERIA: Diagnosis of acute promyelocytic leukemia (APL, or AML M3 subtype) per WHO classification
* PRE-SCREENING EXCLUSION CRITERIA: AML with FLT3 mutations that qualify for standard of care treatment with 7+3 and midostaurin (e.g. FLT3 ITD or TKD with allelic ratio \> 0.05)
* PRE-SCREENING EXCLUSION CRITERIA: Favorable risk AML: inv(16), t(8;21), NPM1 mutations without FLT3-ITD, or in-frame mutations (mono- or biallelic) affecting the basic leucine zipper region of CEBPA
* PRE-SCREENING EXCLUSION CRITERIA: Any cancer-directed therapy within 2 weeks prior to starting planned 7+3 induction regimen, with the exception of hydroxyurea, which is allowed to control white blood cell count, or empiric all-trans retinoic acid (ATRA) for suspected APL
* PRE-SCREENING EXCLUSION CRITERIA: Prior receipt of a selective FGFR inhibitor
* PRE-SCREENING EXCLUSION CRITERIA: Known liver disease
* PRE-SCREENING EXCLUSION CRITERIA: History of calcium and phosphate hemostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues
* Except for commonly observed calcifications in soft tissues such as the skin, kidney tendon, or vessels due to injury, disease, or aging in the absence of systemic mineral imbalance)
* PRE-SCREENING EXCLUSION CRITERIA: History of hypovitaminosis D being actively treated with supraphysiologic doses (e.g., 50,000 IU/weekly) to replenish the deficiency. Supraphysiologic doses of vitamin D need to be discontinued prior to starting pemigatinib. Vitamin D supplements are allowed
* PRE-SCREENING EXCLUSION CRITERIA: Untreated human immunodeficiency virus (HIV) or active hepatitis C detectable by PCR, or chronic hepatitis B
* Individuals positive for hepatitis B core antibody who are receiving intravenous immunoglobulin (IVIg) are eligible if HepB PCR is negative
* PRE-SCREENING EXCLUSION CRITERIA: History of cerebrovascular accident or intracranial hemorrhage within 2 months of enrollment
* PRE-SCREENING EXCLUSION CRITERIA: Unwillingness to receive infusion of blood products
* PRE-SCREENING EXCLUSION CRITERIA: Inability to take oral medication
* PRE-SCREENING EXCLUSION CRITERIA: Gastrointestinal condition/disorders that may raise gastric and/or small intestinal pH that could interfere with absorption, metabolism, or excretion of pemigatinib
* PRE-SCREENING EXCLUSION CRITERIA: Known history and/or current evidence of ectopic mineralization/calcification, including (but not limited to): soft tissue, kidneys, intestine, myocardia, or lung, excepting calcified lymph nodes and asymptomatic arterial or cartilage/tendon calcification
* PRE-SCREENING EXCLUSION CRITERIA: Concurrent active malignancy with expected survival of \< 1 year
* PRE-SCREENING EXCLUSION CRITERIA: Active central nervous system involvement with AML
* TREATMENT EXCLUSION CRITERIA: Clinically significant coagulation abnormality (e.g., disseminated intravascular coagulation) that is present on or by day 8 of induction therapy prior to starting pemigatinib
* TREATMENT EXCLUSION CRITERIA: Clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months from day 1 of planned induction therapy, New York Heart Association class III or IV congestive heart failure, and uncontrolled arrhythmia (participants with pacemaker or with atrial fibrillation and well controlled heart rate are allowed). History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful.
* A screening QT interval by Fridericia's Correction Formula (QTcF) interval \> 480 ms will result in exclusion.
* For participants with an intraventricular conduction delay (QRS interval \> 120 ms), the JTc interval may be used in place of the QTc with approval from Sponsor-Investigator. The JTc must be =\< 340 ms if JTc is used in place of the QTc.
* TREATMENT EXCLUSION CRITERIA: Left ventricular ejection fraction (LVEF) by echocardiogram \< 45% prior to initiating pemigatinib
* TREATMENT EXCLUSION CRITERIA: Active infection that is not well-controlled by antibacterial or antiviral therapy
* TREATMENT EXCLUSION CRITERIA: Current use of prohibited medications including use of any potent CYP3A4 inducers within 14 days or five half-lives (whichever is longer) before the first dose of study drug.
* Use of CYP3A4 inhibitors should be avoided but, if medically necessary, is permitted with a dose reduction of study drug
* Use of moderate CYP3A4 inhibitors are permitted.
* Based on the low overall bioavailability of topical ketoconazole, there are no restrictions on topical ketoconazole
* TREATMENT EXCLUSION CRITERIA: Current use of prohibited medication
* TREATMENT EXCLUSION CRITERIA: Hypersensitivity to pemigatinib, or its excipients, when administered alone
* TREATMENT EXCLUSION CRITERIA: Current evidence of corneal disorder/keratopathy, including (but not limited to): bullous/band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivitis, etc., as confirmed by ophthalmologic examination.
* TREATMENT EXCLUSION CRITERIA: Pregnancy or breastfeeding at the time of enrollment
* TREATMENT EXCLUSION CRITERIA: Any concurrent condition that, in the investigator's opinion, would jeopardize the safety of the participant or compliance with the protocol
* TREATMENT EXCLUSION CRITERIA: Active central nervous system involvement with AML
* TREATMENT EXCLUSION CRITERIA: Patients with FLT mutations PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspirate, PROCEDURE: Bone Marrow Biopsy, DRUG: Cytarabine, DRUG: Daunorubicin, PROCEDURE: Electrocardiography, DRUG: Pemigatinib
Acute Myeloid Leukemia, Myeloid and Monocytic Leukemia
UT Southwestern
Study of Biomarker-Based Treatment of Acute Myeloid Leukemia
This screening and multi-sub-study Phase 1b/2 trial will establish a method for genomic screening followed by assigning and accruing simultaneously to a multi-study "Master Protocol (BAML-16-001-M1)." The specific subtype of acute myeloid leukemia will determine which sub-study, within this protocol, a participant will be assigned to evaluate investigational therapies or combinations with the ultimate goal of advancing new targeted therapies for approval. The study also includes a marker negative sub-study which will include all screened patients not eligible for any of the biomarker-driven sub-studies.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
All
60 Years and over
Phase 1/Phase 2
NCT03013998
STU 012017-028
Inclusion Criteria:
• Adults, age 60 years or older at the time of diagnosis
• Subjects or their legal representative must be able to understand and provide written informed consent
• Cohort Inclusion Criteria - Group A: Subjects must have previously untreated acute myeloid leukemia (AML) according to the WHO classification with no prior treatment other than hydroxyurea. Prior therapy for myelodysplastic syndrome (MDS), myeloproliferative syndromes (MPD), or aplastic anemia is permitted but not with hypomethylating agents.
• Cohort Inclusion Criteria - Group B: Subjects must have relapsed or refractory AML according to the WHO classification. For study purposes, refractory AML is defined as failure to ever achieve CR or recurrence of AML within 6 months of achieving CR; relapsed AML is defined as all others with disease after prior remission. (Group B is not currently recruiting. Expected to begin recruiting in 3rd quarter 2017.)
Exclusion Criteria:
• Isolated myeloid sarcoma (meaning, patients must have blood or marrow involvement with AML to enter the study)
• Acute promyelocytic leukemia
• Symptomatic central nervous system (CNS) involvement by AML
• Signs of leukostasis requiring urgent therapy
• Disseminated intravascular coagulopathy with active bleeding or signs of thrombosis
• Patients with psychological, familial, social, or geographic factors that otherwise preclude them from giving informed consent, following the protocol, or potentially hamper compliance with study treatment and follow-up
• Any other significant medical condition, including psychiatric illness or laboratory abnormality, that would preclude the patient participating in the trial or would confound the interpretation of the results of the trial
Biological: Samalizumab (BAML-16-001-S1), Biological: BI 836858 (BAML-16-001-S2), Other: Laboratory Biomarker Analysis, Drug: Daunorubicin (BAML-16-001-S1), Drug: Cytarabine (BAML-16-001-S1), Drug: Azacitidine (BAML-16-001-S2), Drug: AG-221 (BAML-16-001-S3), Drug: Azacitidine (BAML-16-001-S3), Drug: Entospletinib (BAML-16-001-S4), Drug: Azacitidine (BAML-16-001-S4), Drug: Entospletinib (BAML-16-001-S5), Drug: Decitabine (BAML-16-001-S5), Drug: Entospletinib (BAML-16-001-S6), Drug: Azacitidine (BAML-16-001-S6), Drug: Daunorubicin (BAML-16-001-S6), Drug: Cytarabine (BAML-16-001-S6), Drug: Pevonedistat (BAML-16-001-S9), Drug: Azacitidine (BAML-16-001-S9)
Previously Untreated Acute Myeloid Leukemia, Leukemia, Other
UT Southwestern
Study of R289 in Patients With Lower-risk Myelodysplastic Syndromes (LR MDS)
The study will be an open-label, Phase 1b study of R289 to determine tolerability and preliminary efficacy in patients with LR MDS who are relapsed, refractory/resistant, intolerant, or have inadequate response to prior therapies such as erythropoietin (EPO), thrombopoietin (TPO), luspatercept, or hypomethylating agents (HMAs) for MDS.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
All
18 Years and over
Phase 1/Phase 2
NCT05308264
STU-2022-0561
Inclusion Criteria:
• Patient must be ≥ 18 years of age at the time of signing the informed consent.
• Must have definitive diagnosis of MDS with very low, low, or intermediate-1 risk (International Prognostic Scoring System (IPSS)-R ≤ 3.5) and ≤5% bone marrow myeloblasts.
• Must be relapsed, refractory/resistant, intolerant, or have inadequate response to therapies with known clinical benefits for MDS, such as TPOs, EPOs, luspatercept, and HMAs(i.e., azacytidine or decitabine). Patients with del (5q) must have failed prior lenalidomide therapy.
• Must meet at least one of the disease-related criteria for RBC transfusion, or platelet count within 8 weeks prior to initial administration of study treatment:
• Symptomatic anemia untransfused with hemoglobin < 9.0 g/dL within 8 weeks of registration or red blood cell (RBC) transfusion dependent defined as receiving ≥ 2 units of packed red blood cells (PRBCs) within 8 weeks in the preceding 16 weeks for a hemoglobin <9.0 g/dL.
• Clinically relevant thrombocytopenia (platelet counts of <100 × 109/L in at least 2 blood counts prior to study treatment and transfusion dependence). All subjects must have documented marrow iron stain. If marrow iron stain is not available, the transferrin saturation must be >20% or a serum ferritin > 100ng/100mL
• Must have Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 at screening.
• Must have adequate organ function, defined as:
• Hepatic function:
• aspartate amino transferase (AST) or alanine aminotransferase (ALT) ≤ 1.5 × upper limit of normal (ULN)
• total bilirubin ≤ 1.5 × ULN
• Renal function defined as creatinine clearance > 60 mL/min (using Cockcroft-Gault), or blood creatine < 1.5 mg/dL
Exclusion Criteria:
• Prior treatment for MDS (i.e., TPOs, EPOs, HMAs) concluded < 2 weeks, luspatercept < 3 weeks, prior to study treatment
• Clinically significant anemia resulting from iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis, or GI bleeding.
• MDS secondary to treatment with radiotherapy, chemotherapy, and/or immunotherapy for malignant or autoimmune diseases.
• Diagnosis of chronic myelomonocytic leukemia.
• History of uncontrolled seizures.
• Uncontrolled bacterial or viral infection (i.e., documented HIV, hepatitis B or hepatitis C).
• History of an active malignancy within the past 2 years prior to study entry, with the exception of:
• Adequately treated in situ carcinoma of the cervix uteri
• Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin, or
• Any other malignancy with a life expectancy of more than 2 years
• History of or active, clinically significant, cardiovascular, respiratory, GI, renal, hepatic, neurological, psychiatric, musculoskeletal, genitourinary, dermatological, or other disorder that, in the Investigator's opinion, could affect the conduct of the study or the absorption, metabolism or excretion of the study treatment.
• Prior history of bone marrow transplantation.
• Marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval > 480 milliseconds [msec]) (Common Terminology Criteria for Adverse Events [CTCAE] Grade 1) using Fridericia's QT correction formula.
• History of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
• Receiving any other concurrent chemotherapy, radiotherapy, or immunotherapy (within 2 weeks of initiating study treatment), or the toxicity of the relevant prior treatment has not been resolved yet.
• Use of concomitant medications that prolong the QT/QTc interval during study treatment
• Use of concomitant medications that are strong CYP3A or CYP2B6 inhibitors or inducers during study treatment
Drug: R906289 Monosodium (R289 Na)
Low Risk Myelodysplastic Syndromes, Myeloid and Monocytic Leukemia
MDS, LR MDS, Myelodysplastic Syndromes, Hematology Oncology, Hem/ Onc
UT Southwestern