Venetoclax and HMA Treatment for FLT3 Mutated AML
This study is for older adults, or adults under 60 who can't tolerate intensive chemotherapy, with acute myeloid leukemia (AML) that has FLT3 mutations. It compares the usual treatment of azacitidine and venetoclax to a new combination that adds gilteritinib. Azacitidine helps activate genes that control cell growth, venetoclax blocks a protein cancer cells need to survive, and gilteritinib works by blocking a substance that helps cancer cells multiply. The main goal is to see if adding gilteritinib leads to more patients achieving a complete remission (when the cancer is no longer detectable) without measurable residual disease (MRDneg) after up to four cycles of treatment. The study plans to enroll 147 participants.
- Study design
- This is an interventional study, comparing different drug combinations. It aims to enroll 147 participants.
- What's involved
- You would undergo blood sample collection, bone marrow biopsies, and bone marrow aspirations. You would receive azacitidine (given intravenously or subcutaneously) and gilteritinib (taken by mouth).
- Compensation
- Not stated in the trial record.
- Follow-up
- The primary outcome measures are assessed up to 4 cycles of treatment.
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NCT06317649
Venetoclax and HMA Treatment of Older and Unfit Adults With FLT3 Mutated Acute Myeloid Leukemia (AML) (A MyeloMATCH Treatment Trial)
Recruiting
PHASE2Ages 18+InterventionalTreatmentNational Cancer Institute (NCI)Government-funded
~147 participants
Updated 2026-08-24 on ClinicalTrials.gov
What's tested:AzacitidineBiospecimen CollectionBone Marrow AspirationBone Marrow BiopsyGilteritinibVenetoclax
At a glance
Recruiting sites
218 of 227 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Rate of measured residual disease (MRD) negative complete remission (CR)
Measured over Up to 4 cycles of treatment (1 cycle = 28 days)
Conditions
Where it's being run
227 sites across 43 statesIllinois29
California24
Michigan15
Wisconsin14
Minnesota11
Idaho10
New Jersey9
New York8
Study leadership
- Jessica K Altman · PRINCIPAL_INVESTIGATOR · ECOG-ACRIN Cancer Research Group
Who to contact
Site Public Contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Patient must be ≥ 60 years of age or adults ˂ 60 who in the opinion of the treating physician are better served by azanucleoside-based therapy rather than intensive, cytarabine-based induction based on clinical status (i.e., performance status), organ dysfunction, or disease biology
Patient must have a morphologically confirmed diagnosis of AML as determined by the site and confirmed by the treatment verification team, excluding acute promyelocytic leukemia (APL) with PML-RARA, AML with RUNX1-RUNX1T1, or AML with CBFB-MYH11
Patient must have no prior therapy for AML with the exception of hydroxyurea, all-trans retinoic acid (ATRA), cytarabine-based emergency therapy or leukapheresis to ensure white blood cells (WBC) \< 25,000/mm\^3 prior to starting venetoclax treatment
Patient must have no prior therapy with hypomethylating agents or FLT3 inhibitors
Patient must have the FLT3-ITD, D835, or I836del mutation based on MYELOMATCH Protocol
Patient must be assigned to this protocol by the MYELOMATCH Protocol
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)
Patients 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 30 days after the last dose of venetoclax for all patients who are able to conceive or father children and for 6 months after the last dose of gilteritinib for patients of childbearing potential and for 4 months after the last dose of gilteritinib for male patients with partners of childbearing potential. Patient must not breastfeed during treatment and for 2 months after treatment ends
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/or family member available will also be considered eligible
Total bilirubin ≤ 2 X institutional upper limit of normal (ULN), unless thought to be elevated due to disease involvement or Gilbert's syndrome, in which case bilirubin ≤ 3 x ULN is allowed (must be obtained ≤ 14 days prior to randomization)
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x institutional ULN (must be obtained ≤ 14 days prior to randomization)
Creatinine clearance ≥ 30 mL/min (must be obtained ≤ 14 days prior to randomization)
Either measured or estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation (2021)
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
Patients who meet the criteria below must have had an electrocardiogram (ECG) performed with a corrected QT interval using Fridericia's correction (QTcF) interval within normal limits:
Patient \< 75 years old with a history of cardiac arrythmia, atrial fibrillation, or irregular QTcF interval OR
Patient \< 75 years old with known genetic predisposition to long QT syndrome OR
Any patient ≥ 75 years old OR
Any patient at risk for electrolyte abnormalities, including tumor lysis syndrome
Normal limits are QTcF ≤ 450 ms for males and QTcF ≤ 460 ms for females. Corrected QT interval method (QTcF) may follow institutional standards
NOTE: Since older patients and patients with cardiac disease are at risk for prolonged QTcF and many will require supportive care with agents that affect the QTcF, an ECG is recommended if clinically indicated as noted above. If the QTcF is prolonged (\> 450 ms for males and \> 460 ms for females), they should be treated on the Tier Advancement Pathway (TAP) instead of MM1OA-EA02. In patients where ECG is not clinically indicated, QTcF does not need to be documented
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
Patient must not have the medical necessity for ongoing treatment with a strong CYP3A4 inducing drug
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
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2 or better
Patient must not have an uncontrolled infection
What this trial measures
- Rate of measured residual disease (MRD) negative complete remission (CR)Up to 4 cycles of treatment (1 cycle = 28 days)
Will be assessed by multiparameter flow cytometry at a level of ≤ 1 residual blast / 1,000 leukocytes (≤ 10\^-3). Patients achieved MRD negative CR at any time up to 4 cycles will count as a responder. The MRD negative CR frequencies will be compared between each triplet regimen and the control regimen using Fisher's exact test with one-sided alpha of 0.05 for each comparison. Test results with one-sided p-value \< 0.05 will be considered statistically significant.