Home › Trials › NCT06317649

Combination treatment for older adults with FLT3 mutated acute myeloid leukemia

A Randomized Phase II Study of Venetoclax and HMA-Based Therapies for the Treatment of Older and Unfit Adults With Newly Diagnosed FLT3-Mutated Acute Myeloid Leukemia (AML): A MyeloMATCH Treatment Trial

PHASE2 · National Cancer Institute (NCI) · NCT06317649

This study is testing a new combination treatment for older adults with a specific type of leukemia to see if it helps them achieve better remission compared to the standard treatment.

Quick facts

PhasePHASE2
Study typeInterventional
Enrollment147 (estimated)
Ages18 Years and up
SexAll
SponsorNational Cancer Institute (NCI) (nih)
Drugs / interventionsgilteritinib
Locations221 sites (Tucson, Arizona and 220 other locations)
Trial IDNCT06317649 on ClinicalTrials.gov

What this trial studies

This phase II MyeloMATCH treatment trial evaluates the effectiveness of a combination therapy involving azacitidine, venetoclax, and gilteritinib compared to the standard treatment of azacitidine and venetoclax alone in older and unfit patients with acute myeloid leukemia (AML) harboring FLT3 mutations. The study aims to determine if the triplet regimen can achieve a higher rate of measurable residual disease negative complete remission within four cycles of therapy. Additionally, it will assess the safety and tolerability of the combination treatment and explore the optimal sequence and duration of gilteritinib. The trial also includes exploratory objectives to measure the reduction in FLT3 mutation burden using advanced sequencing techniques.

Who should consider this trial

Good fit: Ideal candidates are adults aged 60 and older, or younger patients deemed unsuitable for intensive therapy, with a confirmed diagnosis of FLT3 mutated acute myeloid leukemia.

Not a fit: Patients with acute promyelocytic leukemia or those who have received prior therapy with hypomethylating agents or FLT3 inhibitors may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could lead to improved remission rates and better outcomes for older patients with FLT3 mutated AML.

How similar studies have performed: Other studies have shown promising results with similar combination therapies in treating acute myeloid leukemia, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* 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, age \> 75 years), organ dysfunction, or disease biology
* Patient must have a morphologically confirmed diagnosis of AML according to the World Health Organization (WHO) 2016 classification 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 and all-trans retinoic acid (ATRA), or leukapheresis. Patients with cytarabine-based emergency therapy prior to the start of therapy on this trial are eligible
* Patient must have no prior therapy with hypomethylating agents or FLT3 inhibitors
* Patient must have the FLT3-ITD or D835 mutation based on MyeloMATCH Master Screening and Reassessment Protocol (MSRP)
* Patient must be assigned to this protocol by the myeloMATCH MSRP
* 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 registration to rule out pregnancy.
  * A patient of childbearing potential is defined as anyone, regardless of sexual orientation or 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)
* Patient of childbearing potential and/or sexually active patients must not expect to conceive or father children by using an 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 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 2X ≤ institutional upper limit of normal (ULN) (unless thought to be elevated due to disease involvement or Gilbert's syndrome)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x institutional ULN

  * Either measured or estimated by Cockcroft-Gault equation
* Creatinine clearance of ≥ 30 mL/min/1.73m\^2
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration/randomization are eligible for this trial
* Patients must not have a baseline corrected QT interval ≥ 480 msec using Fredericia correction (QTcF).

NOTE: Since older patients are at risk for prolonged QTc and many will require supportive care with agents that affect the QTc, an ECG is recommended if clinically indicated. If the QTc is prolonged, they should be treated on tier advancement process (TAP) instead of EA02

* 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 2B or better
* Patients must not have an active or uncontrolled infection

Where this trial is running

Tucson, Arizona and 220 other locations

+171 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Acute Myeloid Leukemia

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.