Comparing Cytarabine + Daunorubicin Therapy Versus Cytarabine + Daunorubicin + Venetoclax Versus Venetoclax + Azacitidine in Younger Patients With Intermediate Risk AML (A MyeloMATCH Treatment Trial)

Recruiting now · Phase 2

Conditions studied: Acute Myeloid Leukemia

In brief

This phase II MyeloMATCH treatment trial compares cytarabine with daunorubicin versus cytarabine with daunorubicin and venetoclax versus venetoclax with azacitidine for the treatment of younger patients with intermediate risk acute myeloid leukemia (AML). Cytarabine is a drug that inhibits some of the enzymes needed for deoxyribonucleic acid (DNA) replication and repair and can slow or stop the growth of cancer cells. Daunorubicin is a drug that blocks a certain enzyme needed for cell division and DNA repair, and it may kill cancer cells. 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. Azacitidine is a drug that interacts with DNA to activate tumor-suppressing genes, resulting in an anti-tumor effect. Adding venetoclax to cytarabine and daunorubicin, and adding venetoclax to azacitidine, may work better than the usual treatment of cytarabine with daunorubicin alone. To decide if they are better, the study doctors are looking to see if venetoclax increases the rate of elimination of AML in participants by 20% or more compared to the usual approach.

Key facts

Study ID

NCT05554393

Run by

National Cancer Institute (NCI)

People needed

153

Starts

2024-09-13

Expected to finish

2027-12-31

Last updated by the study team

2026-08-05

Who can join

Age: 18 and older, up to 59. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Participants must have been registered to master screening and re-assessment protocol (MYELOMATCH) 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 and must be offered the opportunity to submit biosamples for banking for future research as per MYELOMATCH
• Note: Pre-enrollment/diagnosis labs must have already been performed under MYELOMATCH
• Previously untreated, de novo acute myeloid leukemia (AML) defined by >= 20% myeloblasts in the peripheral blood or bone marrow (as defined by the current 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 mutation
• 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 10 days of enrollment)
• Aspartate aminotransferase (AST) (serum glutamate pyruvate transaminase [SGPT]) and/or alanine aminotransferase (ALT) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 3 × institutional ULN (must be done within 10 days of enrollment)
• Cardiac ejection fraction >= 50% (echocardiography or MUGA) (if clinically indicated must be done within 14 days of enrollment)
• Calculated creatinine clearance >= 30 mL/min; Clearance to be calculated using Cockcroft formula (must be done within 10 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 prior to the initiation of protocol therapy. Hydroxyurea +/- no more than a total of 2500 mg cytarabine over a total of multiple days 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

You may not qualify if…

• 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 it is running

• University of Alabama at Birmingham Cancer Center — Birmingham, Alabama, United States (enrolling)
• University of Arizona Cancer Center-North Campus — Tucson, Arizona, United States (enrolling)
• University of Arkansas for Medical Sciences — Little Rock, Arkansas, United States (enrolling)
• Banner University Medical Center - Tucson — Tucson, Arizona, United States (enrolling)
• Cedars-Sinai Medical Center — Los Angeles, California, United States (enrolling)
• UCSF Medical Center-Parnassus — San Francisco, California, United States (enrolling)
• Miami Cancer Institute — Miami, Florida, United States (enrolling)
• Memorial Hospital West — Pembroke Pines, Florida, United States (enrolling)
• Phoebe Putney Memorial Hospital — Albany, Georgia, United States (enrolling)
• Saint Alphonsus Cancer Care Center-Boise — Boise, Idaho, United States (enrolling)
• Saint Luke's Cancer Institute - Boise — Boise, Idaho, United States (enrolling)
• Saint Alphonsus Cancer Care Center-Caldwell — Caldwell, Idaho, United States (enrolling)
• Kootenai Health - Coeur d'Alene — Coeur d'Alene, Idaho, United States (enrolling)
• Saint Luke's Cancer Institute - Fruitland — Fruitland, Idaho, United States (enrolling)
• Saint Luke's Cancer Institute - Meridian — Meridian, Idaho, United States (enrolling)
• Saint Alphonsus Cancer Care Center-Nampa — Nampa, Idaho, United States (enrolling)
• Saint Luke's Cancer Institute - Nampa — Nampa, Idaho, United States (enrolling)
• Kootenai Clinic Cancer Services - Post Falls — Post Falls, Idaho, United States (enrolling)
• Kootenai Clinic Cancer Services - Sandpoint — Sandpoint, Idaho, United States (enrolling)
• Centralia Oncology Clinic — Centralia, Illinois, United States (enrolling)
• Northwestern University — Chicago, Illinois, United States (enrolling)
• University of Chicago Comprehensive Cancer Center — Chicago, Illinois, United States (enrolling)
• Cancer Care Specialists of Illinois - Decatur — Decatur, Illinois, United States (enrolling)
• Decatur Memorial Hospital — Decatur, Illinois, United States (enrolling)
• Crossroads Cancer Center — Effingham, Illinois, United States (enrolling)

Full record on ClinicalTrials.gov

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