RecruitingPhase 2

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

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years to 59 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Time periods mentioned: 1 year
  • Procedures mentioned: Blood draws

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "Patients also undergo bone marrow aspiration and collection of blood samples on study and as clinically indicated."
  • "After completion of study treatment, patients are followed up at 4 weeks, every 3 months for 1 year every 6 months for the second year and yearly thereafter."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study is for adults ages 18–59 with untreated, intermediate-risk acute myeloid leukemia (AML), a cancer of the blood and bone marrow. It compares three drug combinations: cytarabine plus daunorubicin, those two drugs plus venetoclax, and venetoclax plus azacitidine. Doctors want to see if the combinations with venetoclax clear AML better than the usual two-drug treatment.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be ages 18–59 when starting treatment, with newly diagnosed AML and at least 20% immature leukemia cells in the blood or bone marrow.
  • Complete MYELOMATCH screening, be assigned to this study, and agree to provide research samples.
  • Meet limits for daily activity and self-care, and pass required liver, kidney, and heart checks.
  • Have a white blood cell count of 25 billion per liter or less. Certain treatments to lower this count are allowed before study treatment.
  • If you have HIV or hepatitis B or C, meet the study’s treatment and virus-level rules.
  • If you or your partner could become pregnant, agree to use highly effective birth control during treatment and for 6 months after stopping study drugs. Pregnancy testing is required for those who could become pregnant.
  • Sign a consent form and be able to attend treatment, testing, and follow-up at the study center. Treatment must start within 7 working days after enrollment.
  • AML in the brain or spinal cord is allowed. Another cancer is allowed if it will not affect study safety or results.

Who can't join

  • AML with certain gene or chromosome changes that the study rules out. Screening tests check for these changes.
  • AML caused by past cancer treatment, or AML that developed after certain other bone marrow diseases.
  • Prior AML treatment, except certain short-term treatments allowed by the study to lower blood counts or while checking for another type of leukemia.
  • Taking another experimental drug.
  • A past allergic reaction to drugs similar to any of the study drugs.
  • Being pregnant. Breastfeeding must stop during study treatment.
  • Having only myeloid sarcoma—a tumor of leukemia cells outside the bone marrow.
  • A serious illness or organ problem that makes treatment unsafe, including an active infection that is not controlled.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

Inclusion Criteria: * 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 * 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

Study sites (175)

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AR

AZ

CA

CT

FL

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IA

  • University of Iowa/Holden Comprehensive Cancer Center · Iowa City, IA 52242Site Public Contact · Study contact · 800-237-1225Prajwal Dhakal · Principal investigatorMore trials in Iowa City

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IL

IN

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KY

LA

MA

MD

  • Walter Reed National Military Medical Center · Bethesda, MD 20889-5600Site Public Contact · Study contact · 301-319-2100Ryan Jones · Principal investigatorMore trials in Bethesda

ME

MI

MN

MO

MS

MT

NC

NE

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NJ

NM

NV

NY

OH

OK

OR

PA

RI

SC

TN

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VT

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WI