[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100659237":3},{"organization":4,"outcomesModule":7,"designInfo":37,"detailedDescription":43,"studyPopulation":16,"armGroups":44,"interventions":63,"overallOfficials":201,"centralContacts":16,"locations":16,"responsibleParty":206,"collaborators":16,"id":208,"slug":209,"hasResults":210,"nctId":211,"briefTitle":212,"officialTitle":213,"acronym":16,"eligibilityCriteria":214,"healthyVolunteers":210,"sex":215,"minAge":216,"maxAge":217,"enrollmentInfo":218,"targetDuration":16,"studyType":221,"phases":222,"briefSummary":224,"conditions":225,"keywords":16,"overallStatus":227,"whyStopped":16,"lastUpdateSubmitDate":228,"lastUpdatePostDateStruct":229,"startDateStruct":232,"completionDateStruct":234,"leadSponsor":236,"locationsCount":16},{"fullName":5,"class":6},"National Cancer Institute (NCI)","NIH",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":16},[9],{"measure":10,"description":11,"timeFrame":12},"Rate of measurable residual disease (MRD) negative complete response (CR)","As measured by multiparameter flow cytometry.","After completion of 2 treatment cycles (cycle length = 28 days)",[14,18,21,23,27,30,34],{"measure":15,"description":16,"timeFrame":17},"Rate of MRD negative CR\u002Fcomplete remission incomplete hematologic recovery (CRi)",null,"Up to 5 years",{"measure":19,"description":20,"timeFrame":17},"MRD negative CR","Measured by Molecular Diagnostic Network next generation sequencing assay.",{"measure":22,"description":16,"timeFrame":17},"MRD negative composite complete response",{"measure":24,"description":25,"timeFrame":26},"Event free survival","Will be calculated using the Kaplan-Meier method.","From randomization to failure to achieve CR\u002FCRi, or to relapse after CR\u002FCRi or to death in remission, assessed up to 5 years",{"measure":28,"description":25,"timeFrame":29},"Overall survival","From randomization to death, assessed up to 5 years",{"measure":31,"description":32,"timeFrame":33},"30-day mortality rate","Will be compared between the treatment arms using Fisher's exact test.","At 30 days",{"measure":35,"description":36,"timeFrame":17},"Incidence of adverse events","Will be determined using the Common Terminology Criteria for Adverse Events.",{"allocation":38,"interventionModel":39,"interventionModelDescription":16,"primaryPurpose":40,"observationalModel":16,"timePerspective":16,"maskingInfo":41},"RANDOMIZED","PARALLEL","TREATMENT",{"masking":42,"maskingDescription":16,"whoMasked":16},"NONE","PRIMARY OBJECTIVE:\n\nI. To determine if measurable residual disease (MRD) negative complete response (CRMRD-) rate, as measured by multiparameter flow cytometry after 2 treatment cycles, for patients with FLT3-ITD mutated acute myeloid leukemia (AML) who receive azacitidine\u002Fvenetoclax\u002Fquizartinib is non-inferior to those who receive quizartinib\u002Fcytarabine\u002Fdaunorubicin during induction.\n\nSECONDARY OBJECTIVES:\n\nI. To compare the MRD- composite complete response rate (CRc) (complete response \\[CR\\]+complete remission incomplete hematologic recovery \\[CRi\\]) in patients who receive azacitidine\u002Fvenetoclax\u002Fquizartinib versus (vs) quizartinib\u002Fcytarabine\u002Fdaunorubicin.\n\nII. To compare the FLT3-ITD mutation undetectable CRc (CR+CRi) rate of patients with FLT3-ITD mutated AML who receive azacitidine\u002Fvenetoclax\u002Fquizartinib to those who receive quizartinib\u002Fcytarabine\u002Fdaunorubicin during induction as measured by Molecular Diagnostic Network (MDNet) next generation sequencing (NGS) assay.\n\nIII. To compare the transplantation rate of MRD- CRc (evaluated by flow cytometry) patients with FLT3-ITD mutated AML who receive azacitidine\u002Fvenetoclax\u002Fquizartinib to those who receive quizartinib\u002Fcytarabine\u002Fdaunorubicin during induction.\n\nIV. To compare the CRc (CR+CRi) rate of patients with FLT3-ITD mutated AML who receive azacitidine\u002Fvenetoclax\u002Fquizartinib vs quizartinib\u002Fcytarabine\u002Fdaunorubicin.\n\nV. To compare the event free survival (EFS) of patients with FLT3-ITD mutated AML who receive azacitidine\u002Fvenetoclax\u002Fquizartinib to those who receive quizartinib\u002Fcytarabine\u002Fdaunorubicin and intermediate dose cytarabine\u002Fquizartinib during consolidation.\n\nVI. To compare the overall survival (OS) of patients with FLT3-ITD mutated AML who receive azacitidine\u002Fvenetoclax\u002Fquizartinib to those who receive quizartinib\u002Fcytarabine\u002Fdaunorubicin during induction and intermediate dose cytarabine\u002Fquizartinib during consolidation.\n\nVII. To compare the 30-day mortality of azacitidine\u002Fvenetoclax\u002Fquizartinib to quizartinib\u002Fcytarabine\u002Fdaunorubicin during induction and consolidation in this patient population.\n\nVIII. To compare the toxicities of quizartinib plus standard therapy during induction and consolidation in this patient population in the form of total hospital days and total intensive care unit (ICU) days in cycle 1 and cycle 2 to the total hospital days and total ICU days in cycle 1 and cycle 2 azacitidine\u002Fvenetoclax\u002Fquizartinib.\n\nOUTLINE: Patients are randomized to 1 of 2 arms.\n\nARM A:\n\nINDUCTION: Patients receive cytarabine intravenously (IV), over 24 hours, on days 1-7, daunorubicin IV on days 1-3, and quizartinib orally (PO) once daily (QD) on days 8-21 in the absence of disease progression or unacceptable toxicity. Patients then undergo bone marrow aspiration\u002Fbiopsy. Patients with ≥ 20% bone marrow cellularity and \\> 5% bone marrow leukemic blasts may repeat induction as described starting on day 28-45. Patients with ≥ 20% bone marrow cellularity and ≤ 5% bone marrow leukemic blasts proceed to consolidation, following count recovery, by 30 days post-confirmation of CR\u002FCRi. Patients with \\\u003C 20% bone marrow cellularity and \\> 5% bone marrow leukemic blasts repeat the bone marrow aspiration\u002Fbiopsy 1 week later and then either repeat induction or proceed to consolidation, based on results. Patients with \\\u003C 20% bone marrow cellularity and ≤ 5% bone marrow leukemic blasts proceed to consolidation.\n\nCONSOLIDATION: Patients receive cytarabine IV, over 1-3 hours, every 12 hours on days 1, 3 and 5 and quizartinib PO QD on days 6-19 in the absence of disease progression or unacceptable toxicity.\n\nARM B:\n\nCYCLE 1: Patients receive azacitidine IV or subcutaneously (SC) on days 1-7 or days 1-5 and 8-9, venetoclax PO QD on days 1-28, and quizartinib PO QD on days 1-28 in the absence of disease progression or unacceptable toxicity and based on bone marrow findings. Patients undergo bone marrow aspiration\u002Fbiopsy on day 14 of cycle 1. Patients with ≥ 20% bone marrow cellularity and \\> 5% bone marrow leukemic blasts continue treatment as described through day 28 of cycle 1 and then proceed to cycle 2 without interruption or delay, as long as repeat bone marrow aspiration\u002Fbiopsy on day 28 of cycle 1 is consistent with persistent blasts \\> 5%. Patients with ≥ 20% bone marrow cellularity and ≤ 5% bone marrow leukemic blasts interrupt venetoclax and quizartinib for the remainder of the cycle (through day 28) and then proceed to cycle 2 of treatment as described following count recovery. Patients without count recovery by day 42 undergo repeat bone marrow aspiration\u002Fbiopsy. Patients with count recovery by day 42 proceed to cycle 2 (by day 50). For patients without count recovery by day 50 whose repeat bone marrow aspiration\u002Fbiopsy shows no blasts, initiation of cycle 2 will be discussed with the study chairs. Patients with \\\u003C 20% bone marrow cellularity and \\> 5% bone marrow leukemic blasts interrupt venetoclax and quizartinib, undergo repeat bone marrow aspiration\u002Fbiopsy 1 week later, and proceed based on repeat biopsy results as described. Patients with \\\u003C 20% bone marrow cellularity and ≤ 5% bone marrow leukemic blasts interrupt venetoclax and quizartinib for the remainder of the cycle (through day 28) and then proceed to cycle 2 of treatment as described following count recovery. Patients without count recovery by day 42 undergo repeat bone marrow aspiration\u002Fbiopsy. Patients with count recovery by day 42 proceed to cycle 2 (by day 50). For patients without count recovery by day 50 whose repeat bone marrow aspiration\u002Fbiopsy shows no blasts, initiation of cycle 2 will be discussed with the study chairs.\n\nCYCLE 2: Patients receive azacitidine IV or SC on days 1-7 or days 1-5 and 8-9, venetoclax PO QD on days 1-28, and quizartinib PO QD on days 1-28 in the absence of disease progression or unacceptable toxicity and based on bone marrow findings. Patients who do not achieve response after completion of cycle 1 undergo bone marrow aspiration\u002Fbiopsy on day 14 of cycle 2. Patients with ≥ 20% bone marrow cellularity and \\> 5% bone marrow leukemic blasts continue venetoclax and quizartinib as described through day 28 of cycle 2. Patients with ≥ 20% bone marrow cellularity and ≤ 5% bone marrow leukemic blasts interrupt venetoclax and quizartinib for the remainder of the cycle (through day 28). Patients with \\\u003C 20% bone marrow cellularity and \\> 5% bone marrow leukemic blasts interrupt venetoclax and quizartinib, undergo repeat bone marrow aspiration\u002Fbiopsy 1 week later, and proceed based on repeat aspiration\u002Fbiopsy results as described. Patients with \\\u003C 20% bone marrow cellularity and ≤ 5% bone marrow leukemic blasts interrupt venetoclax and quizartinib for the remainder of the cycle (through day 28).\n\nUpon completion of two cycles of therapy on either Arm A or Arm B, patients who are eligible can proceed to allogeneic stem cell transplant; while awaiting allogeneic stem cell transplant, patients should continue standard of care therapy.\n\nPatients undergo echocardiography or multigated acquisition (MUGA) scan during screening and undergo bone marrow aspiration and biopsy as well as blood sample collection throughout the study.\n\nAfter completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for years 2-5.",[45,58],{"label":46,"type":47,"description":48,"interventionNames":49},"Arm A (cytarabine, daunorubicin, quizartinib)","EXPERIMENTAL","See Detailed Description.",[50,51,52,53,54,55,56,57],"Procedure: Biospecimen Collection","Procedure: Bone Marrow Aspiration","Procedure: Bone Marrow Biopsy","Drug: Cytarabine","Drug: Daunorubicin","Procedure: Echocardiography Test","Procedure: Multigated Acquisition Scan","Drug: Quizartinib",{"label":59,"type":47,"description":48,"interventionNames":60},"Arm B (azacitidine, venetoclax, quizartinib)",[61,50,51,52,55,56,57,62],"Drug: Azacitidine","Drug: Venetoclax",[64,81,91,95,102,139,149,156,174,187],{"type":65,"name":66,"description":67,"armGroupLabels":68,"otherNames":69},"DRUG","Azacitidine","Given IV or SC",[59],[70,71,72,73,74,75,76,77,78,79,80],"5 AZC","5-AC","5-Azacitidine","5-Azacytidine","5-AZC","Azacytidine","Azacytidine, 5-","Ladakamycin","Mylosar","U-18496","Vidaza",{"type":82,"name":83,"description":84,"armGroupLabels":85,"otherNames":86},"PROCEDURE","Biospecimen Collection","Undergo blood sample collection",[46,59],[87,88,89,90],"Biological Sample Collection","Biospecimen Collected","Sample Collection","Specimen Collection",{"type":82,"name":92,"description":93,"armGroupLabels":94,"otherNames":16},"Bone Marrow Aspiration","Undergo bone marrow aspiration",[46,59],{"type":82,"name":96,"description":97,"armGroupLabels":98,"otherNames":99},"Bone Marrow Biopsy","Undergo bone marrow biopsy",[46,59],[100,101],"Biopsy of Bone Marrow","Biopsy, Bone Marrow",{"type":65,"name":103,"description":104,"armGroupLabels":105,"otherNames":106},"Cytarabine","Given IV",[46],[107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138],".beta.-Cytosine arabinoside","1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone","1-.beta.-D-Arabinofuranosylcytosine","1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone","1-Beta-D-arabinofuranosylcytosine","1.beta.-D-Arabinofuranosylcytosine","2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-","2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-","Alexan","Ara-C","ARA-cell","Arabine","Arabinofuranosylcytosine","Arabinosylcytosine","Aracytidine","Aracytin","Aracytine","Beta-Cytosine Arabinoside","CHX-3311","Cytarabinum","Cytarbel","Cytosar","Cytosine Arabinoside","Cytosine-.beta.-arabinoside","Cytosine-beta-arabinoside","Erpalfa","Starasid","Tarabine PFS","U 19920","U-19920","Udicil","WR-28453",{"type":65,"name":140,"description":104,"armGroupLabels":141,"otherNames":142},"Daunorubicin",[46],[143,144,145,146,147,148],"Daunomycin","Daunorrubicina","DNR","Leukaemomycin C","Rubidomycin","Rubomycin C",{"type":82,"name":150,"description":151,"armGroupLabels":152,"otherNames":153},"Echocardiography Test","Undergo echocardiography",[46,59],[154,155],"EC","Echocardiography",{"type":82,"name":157,"description":158,"armGroupLabels":159,"otherNames":160},"Multigated Acquisition Scan","Undergo MUGA scan",[46,59],[161,162,163,164,165,166,167,168,169,170,171,172,173],"Blood Pool Scan","Equilibrium Radionuclide Angiography","Gated Blood Pool Imaging","Gated Heart Pool Scan","MUGA","MUGA Scan","Multi-Gated Acquisition Scan","Radionuclide Ventriculogram Scan","Radionuclide Ventriculography","RNV Scan","RNVG","SYMA Scanning","Synchronized Multigated Acquisition Scanning",{"type":65,"name":175,"description":176,"armGroupLabels":177,"otherNames":178},"Quizartinib","Given PO",[46,59],[179,180,181,182,183,184,185,186],"AC 220","AC-220","AC010220","AC220","ASP 2689","ASP-2689","ASP2689","Vanflyta",{"type":65,"name":188,"description":176,"armGroupLabels":189,"otherNames":190},"Venetoclax",[59],[191,192,193,194,195,196,197,198,199,200],"ABT 199","ABT-0199","ABT-199","ABT199","GDC 0199","GDC-0199","GDC0199","RG7601","Venclexta","Venclyxto",[202],{"name":203,"affiliation":204,"role":205},"Keith W Pratz","ECOG-ACRIN Cancer Research Group","PRINCIPAL_INVESTIGATOR",{"type":207,"investigatorFullName":16,"investigatorTitle":16,"investigatorAffiliation":16,"oldNameTitle":16,"oldOrganization":16},"SPONSOR","100659237","phase-2-testing-the-investigational-medication-combination-of-azacitidine-venetoclax-and-quizartinib-compared-to-the-usual-treatment-of-cytarabine-daunorubicin-and-quizartinib-for-patients-with-flt3-itd-mutant-acute-myeloid-leukemia-a-myelomatch-treatment-trial-100659237",false,"NCT07862517","Testing the Investigational Medication Combination of Azacitidine, Venetoclax, and Quizartinib Compared to the Usual Treatment of Cytarabine, Daunorubicin, and Quizartinib for Patients With FLT3-ITD Mutant Acute Myeloid Leukemia (A MyeloMATCH Treatment Trial)","A Phase II Randomized Study of Induction Therapy Comparing Cytarabine, Daunorubicin, and Quizartinib vs Azacitidine, Venetoclax, and Quizartinib in FLT3-ITD Mutant Acute Myeloid Leukemia: A MyeloMATCH Substudy","Inclusion Criteria:\n\n* Patient must be ≥ 18 and ≤ 59 years of age\n* Patient must be assigned to this protocol by the MYELOMATCH Protocol\n* Patient must have newly diagnosed acute myeloid leukemia (AML) with FLT3 ITD mutation as assessed by central myeloMATCH testing with variant allele frequency (VAF) over 5%\n* Patient must not have any contraindications to the conventional chemotherapy used in this study\n* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2\n* Patient must not have Core-binding factor \\[inv(16), t(16;16) or t(8;21)\\] leukemia\n* Patient must not have acute promyelocytic leukemia\n* Patient must not have had prior therapy with deoxyribonucleic acid (DNA) methyltransferase inhibitors (DNMTi) for myelodysplastic syndrome (MDS)\n* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy. A patient of childbearing potential is defined as anyone, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)\n* Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study. Contraception measures must continue for:\n\n  * 7 months after the last dose of quizartinib for patients of childbearing potential and for 4 months after the last dose of quizartinib for patients who are able to father children\n  * 6 months after the last dose of daunorubicin for all patients\n  * 30 days after the last dose of venetoclax for patients of childbearing potential\n  * 6 months after the last dose of azacitidine for patients of childbearing potential and for 4 months after the last dose of azacitidine for patients who are able to father children In addition, patient must not breastfeed during treatment and for 1 month after treatment ends\n* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and\u002For family member available will also be considered eligible\n* Total bilirubin ≤ 2 x institutional upper limit of normal (ULN). Patients with Gilbert's Syndrome must have total bilirubin ≤ 3 x institutional ULN (labs must be obtained ≤ 7 days prior to protocol randomization)\n* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \\[SGOT\\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) ≤ 3.0 × institutional ULN (labs must be obtained ≤ 7 days prior to protocol randomization)\n* Creatinine Clearance (CrCL) ≥ 30 mL\u002Fmin calculated using the Cockcroft-Gault equation (labs must be obtained ≤ 7 days prior to protocol randomization)\n* Left ventricular ejection fraction \\> 45% (which must be obtained ≤ 2 weeks prior to randomization)\n\n  * NOTE: Since quizartinib can increase corrected QT interval (QTc) and many patients will require supportive care agents that affect QTc, a baseline electrocardiogram (ECG) ≤ 2 weeks prior to randomization is recommended if clinically indicated\n* Patient must not have Common Terminology Criteria for Adverse Events (CTCAE) \\> grade 3 hypokalemia, hypomagnesemia, or hypocalcemia. Patients with grade 1-2 electrolyte abnormalities are eligible while electrolytes are being corrected\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* 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\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* Patients must not have had history of treatment with cardiotoxic agents unless total anthracycline lifetime dose is \\\u003C 450 mg\u002Fm\\^2 doxorubicin equivalents\n* Patients must not have uncontrolled or significant cardiovascular disease, including any of the following:\n\n  * Fridericia's formula-corrected QT (QTcF) interval \\> 450 ms;\n  * Diagnosis of or suspicion of long QT syndrome (including family history of long QT syndrome);\n  * Systemic blood pressure \\> 180 mmHg or diastolic blood pressure \\> 110 mmHg;\n  * History of clinically relevant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes);\n  * History of second (Mobitz II) or third degree heart block (patients with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker);\n  * History of uncontrolled angina pectoris or myocardial infarction within 6 months prior to randomization;\n  * History of New York Heart Association class 3 or 4 heart failure;\n  * Complete left bundle branch block\n* Patient must not require treatment with concomitant strong or moderate CYP3A4 inducers\n* Patient must not require treatment with concomitant strong CYP3A4 inhibitors (e.g., antifungal azoles) unless considered necessary for the prevention or treatment of infections - in which a quizartinib dose reduction will be required\n* Patient must not have any known gastrointestinal (GI) disease or prior GI procedure that could interfere with the oral absorption or tolerance of quizartinib or venetoclax, including difficulty swallowing\n* Patient must not have any uncontrolled intercurrent illness or any other significant condition(s) that would make this protocol unreasonably hazardous","ALL","18 Years","59 Years",{"count":219,"type":220},122,"ESTIMATED","INTERVENTIONAL",[223],"PHASE2","This phase II MyeloMATCH treatment trial compares the combination of azacitidine, venetoclax and quizartinib to the standard treatment of cytarabine, daunorubicin and quizartinib for the treatment of patients with FLT3-ITD mutant acute myeloid leukemia. Azacitidine and quizartinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. 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. 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. Giving azacitidine, venetoclax and quizartinib may be more effective than giving cytarabine, daunorubicin and quizartinib for the treatment of patients with FLT3-ITD mutant acute myeloid leukemia.",[226],"Acute Myeloid Leukemia","NOT_YET_RECRUITING","2026-10-06",{"date":230,"type":231},"2026-10-07","ACTUAL",{"date":233,"type":220},"2027-01-15",{"date":235,"type":220},"2027-12-31",{"name":5,"class":6}]