Testing the Effects of Novel Therapeutics for Newly Diagnosed, Untreated Patients With High-Risk Acute Myeloid Leukemia (A MyeloMATCH Treatment Trial)

What this study is about

This phase II MyeloMATCH treatment trial tests whether the standard approach of cytarabine and daunorubicin in comparison to the following experimental regimens works to shrink cancer in patients with high risk acute myeloid leukemia (AML): 1) daunorubicin and cytarabine liposome alone; 2) cytarabine and daunorubicin with venetoclax; 3) azacitidine and venetoclax; 4) daunorubicin and cytarabine liposome and venetoclax. "High-risk" refers to traits that have been known to make the AML harder to treat. Cytarabine is in a class of medications called antimetabolites. It works by slowing or stopping the growth of cancer cells in the body. Daunorubicin is in a class of medications called anthracyclines. It also works by slowing or stopping the growth of cancer cells in the body. Azacitidine is in a class of medications called demethylation agents. It works by helping the bone marrow to produce normal blood cells and by killing abnormal 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. There is evidence that these newer experimental treatment regimens may work better in getting rid of more AML compared to the standard approach of cytarabine and daunorubicin.

Who can join (things the study team will check)

✅ You may be able to join if…

• STEP 1 REGISTRATION:
• 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, prior to registration to this study.
  • Note: Pre-enrollment/diagnosis labs must have already been performed under MYELOMATCH
• Participants must have newly diagnosed, untreated acute myeloid leukemia (AML) per World Health Organization (WHO) criteria
• Participants must have high-risk (adverse) AML per European LeukemiaNet (ELN) 2017 criteria
• Participants with therapy-related AML (t-AML), or with AML evolving from an antecedent hematologic disorder (such as myeloproliferative neoplasm), or AML with myelodysplasia-related changes (AML-MRC) are eligible
• Acute promyelocytic leukemia is excluded
• Participants with favorable or intermediate risk disease are excluded
• Participants with FLT3 mutations (ITD or TKD) are excluded
• Participants with t(9;22) translocation are excluded
• A single dose of intrathecal chemotherapy is allowed prior to study entry
• Prior anthracycline therapy is allowed but must not exceed a cumulative lifetime dose of 200 mg/m\^2 daunorubicin or equivalent. Prior hypomethylating agent (HMA) exposure is allowed, as long as not for AML diagnosis
• Participants must not have received or be currently receiving any prior therapy for acute myeloid leukemia. Hydroxyurea to control the white blood cells (WBC) is allowed prior to registration and initiation of protocol-defined therapy. All trans retinoic acid (ATRA) given until a diagnosis of acute promyelocytic leukemia is ruled out is also allowed.
• Participants must not be receiving or planning to receive any other investigational agents before completing protocol therapy
• Participants must be between 18 and 59 years of age
• Participants must have Zubrod performance status =< 3 as determined by a history and physical (H\&P) completed within 14 days prior to registration
• Participants must have a complete medical history and physical exam within 7 days prior to registration
• Participants must be able to swallow and retain oral medications and have no known gastrointestinal disorders likely to interfere with absorption of oral medications
• Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at time of registration and have undetectable HIV viral load within 6 months prior to registration
• Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load within 28 days prior to registration and be on suppressive therapy, if indicated
• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with active HCV infection who are currently on treatment must have an undetectable HCV viral load within 28 days prior to registration

+ 11 more criteria — see the full checklist in the app.

Where this trial is running

• University of Alabama at Birmingham Cancer Center, Birmingham, Alabama, United States
• Mayo Clinic Hospital in Arizona, Phoenix, Arizona, United States
• Banner University Medical Center - Tucson, Tucson, Arizona, United States
• University of Arizona Cancer Center-North Campus, Tucson, Arizona, United States
• University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
• Alta Bates Summit Medical Center-Herrick Campus, Berkeley, California, United States
• Cedars-Sinai Medical Center, Los Angeles, California, United States
• University of California Davis Comprehensive Cancer Center, Sacramento, California, United States
• UCSF Medical Center-Parnassus, San Francisco, California, United States
• Mills Health Center, San Mateo, California, United States
• Yale University, New Haven, Connecticut, United States
• Mayo Clinic in Florida, Jacksonville, Florida, United States

+ 209 more sites.