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Comparing different treatments for younger patients with intermediate risk acute myeloid leukemia

A Measurable Residual Disease (MRD) Focused, Phase II Study of Venetoclax Plus Chemotherapy for Newly Diagnosed Younger Patients With Intermediate Risk Acute Myeloid Leukemia: A Tier 1 MYELOMATCH SubStudy

Phase 2 Interventional National Cancer Institute (NCI) · NCT05554393

This study is testing different treatment combinations for younger patients with intermediate risk acute myeloid leukemia to see which one helps them achieve better remission and has fewer side effects.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment153 (estimated)
Ages18 Years to 59 Years
SexAll
SponsorNational Cancer Institute (NCI) NIH
Drugs / interventionschemotherapy
Locations177 sites (Birmingham, Alabama and 176 other locations)
Trial IDNCT05554393 on ClinicalTrials.gov

What this trial studies

This phase II MyeloMATCH treatment trial evaluates the effectiveness of three treatment regimens for younger patients with intermediate risk acute myeloid leukemia (AML). The study compares cytarabine and daunorubicin therapy against combinations of these drugs with venetoclax and azacitidine. The primary objective is to assess the rates of undetectable measurable residual disease (MRD) in patients achieving complete remission after induction therapy. Secondary objectives include evaluating treatment toxicities and various survival outcomes, while tertiary objectives focus on genomic findings and long-term outcomes.

Who should consider this trial

Good fit: Ideal candidates for this study are younger patients with previously untreated, de novo acute myeloid leukemia and actionable mutations.

Not a fit: Patients with acute myeloid leukemia who have received prior treatment or do not have actionable mutations may not benefit from this study.

Why it matters

Potential benefit: If successful, this trial could lead to more effective treatment options for younger patients with intermediate risk AML, potentially improving remission rates and overall survival.

How similar studies have performed: Other studies have shown promise with similar treatment combinations, suggesting potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Patient must have enrolled onto MYELOMATCH and must have been given a treatment assignment to MyeloMATCH to MM1YA-CTG01 based on the presence of an actionable mutation as defined in MYELOMATCH
* Participants must have been registered to master screening and re-assessment protocol (myeloMATCH MSRP) prior to consenting to this study. Participants must have been assigned to this clinical trial, via MATCHBox Protocol Assignment Team, prior to registration to this study. Participants must have agreed to have specimens submitted for translational medicine (MRD) and must be offered the opportunity to submit biosamples for banking for future research as per the myeloMATCH MSRP

  * Note: Pre-enrollment/diagnosis labs must have already been performed under the MSRP
* Previously untreated, de novo acute myeloid leukemia (AML) defined by \> 20% myeloblasts in the peripheral blood or bone marrow (refer to the 2016 updated World Health Organization \[WHO\] classification of myeloid neoplasms and acute leukemia) excluding all the following categories of AML:

  * Favorable cytogenetics: (t(8;21)q22;q22.1); RUNX1-RUNX1T1, inversion 16(p13.1;q22), t(16;16)(p13.1;q22); CBFB-MYH11
  * CEBPA biallelic mutations
  * NPM1 mutation
  * AML with PML-RARalpha
  * AML with any adverse cytogenetics, TP53 mutation, RUNX1 mutation, ASXL1, 11q23/KMT2 rearrangements
  * AML with FLT3-ITD or FLT3-TKD mutations
  * Therapy related AML, or AML following a diagnosis of myelodysplasia or myeloproliferative neoplasm Participants with central nervous system (CNS) disease are eligible for this trial and will be treated according to institutional guidelines with intrathecal chemotherapy for this aspect of their disease
* Age 18-59 years at time of induction therapy
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 3
* Total bilirubin =\< 2 x institutional upper limit of normal (ULN) (must be done within 7 days of enrollment)
* Aspartate aminotransferase (AST) (serum glutamate pyruvate transaminase \[SGPT\]) +/or alanine aminotransferase (ALT) (serum glutamic-oxaloacetic transaminase \[SGOT\]) =\< 3 × institutional ULN (must be done within 7 days of enrollment)
* Cardiac ejection fraction \>= 50% (echocardiography or multigated acquisition scan \[MUGA\]) (if clinically indicated must be done within 14 days of enrollment)
* Calculated creatinine clearance \>= 30 mL/min/ 1.73m\^2; Clearance to be calculated using Cockcroft formula (must be done within 7 days of enrollment)
* White blood cells (WBC) must be \< 25 x 10\^9/L. Hydroxyurea and leukapheresis are permitted to control the WBC prior to enrollment and initiation of protocol-defined therapy but must be stopped at least 24 hours prior to the initiation of protocol therapy. 1 dose of cytarabine at 1 mg/m\^2 for urgent cytoreduction is also permitted
* 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
* Males and females of reproductive potential must have agreed to use a highly effective contraceptive method while on treatment and for 6 months after stopping study drug. A woman is considered to be of "childbearing 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, or vasectomy/vasectomized partner. 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.

Women of childbearing potential will have a pregnancy test to determine eligibility as part of the pre-study evaluation; this may include an ultrasound to rule-out pregnancy if a false-positive is suspected. Patient will be considered eligible if an ultrasound is negative for pregnancy

* Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate
* Patients must be accessible for treatment, response assessment and follow up. Patients enrolled on this trial must be treated and followed at the participating centre. Investigators must assure themselves the patients enrolled on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.

Patients must agree to return to their primary care facility for any adverse events which may occur through the course of the trial

* In accordance with Canadian Cancer Trials Group (CCTG) policy, protocol treatment is to begin within 7 working days of patient enrollment
* Participants receiving strong or moderate CYP3A inhibitors must agree to discontinue use at least 48 hours prior to start of study treatment if assigned to arm 1 or 2
* Patients with known human immunodeficiency virus (HIV) infection who are on effective anti-retroviral therapy and have undetectable viral load within 6 months of enrollment are eligible for this trial
* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load within 28 days of enrollment. Patients need to be on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection who have been treated and cured are eligible. Patients who with active HCV infection who are currently being treated must have an undetectable HCV viral load within 28 days of enrollment to be eligible

Exclusion Criteria:

* Prior therapy for AML except for hydroxyurea and leukapheresis to control blood counts. The use of all-trans retinoic acid (ATRA) is permitted until a diagnosis of acute promyelocytic leukemia, if suspected, is ruled out
* Patients who are receiving any other investigational agents
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to cytarabine, daunorubicin, azacitidine, venetoclax
* Pregnant women are excluded from this study because venetoclax, cytarabine and azacitidine have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with venetoclax, cytarabine and azacitidine breastfeeding should be discontinued if the mother is treated with venetoclax, cytarabine and azacitidine. These potential risks may also apply to other agents used in this study
* Patients with isolated myeloid sarcoma are not eligible
* Any other serious intercurrent illness, life threatening condition, organ system dysfunction, or medical condition judged by the local investigator to compromise the subject's safety (for example):

  * Active, uncontrolled bacterial, fungal, or viral infection

Where this trial is running

Birmingham, Alabama and 176 other locations

+127 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 → Find more trials like this →
Conditions Acute Myeloid Leukemia
Last reviewed 2026-06-13 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.