PRIMARY OBJECTIVE:~I. To evaluate the feasibility of MATCHBox generating all data needed for assignment to a myeloMATCH clinical trial or determination that no assignment is available, within 72 hours of MDNet receipt of specimens for initial therapy and within 10 days for subsequent therapy.~SECONDARY OBJECTIVES:~I. To describe the time to generation of all treatment assignment data, time to treatment assignment, percent assigned to a myeloMATCH clinical trial, and the percent of screened participants who register to a myeloMATCH clinical trial:~Ia. For the first Tier 1 myeloMATCH clinical trial assignment; Ib. For Tiers 2, 3, and 4 myeloMATCH clinical trial assignment; Ic. Within each tier of myeloMATCH clinical trials; Id. Within each clinical basket of myeloMATCH clinical trials; Ie. Over time, across and within the categories above.~OUTLINE:~REGISTRATION: Patients undergo bone marrow aspiration and collection of blood on study. Patients' bone marrow and blood specimens undergo rapid genetic testing. Patients are then assigned to a specific protocol containing a therapy targeted to the patient's mutational profile. If there is no targetable mutation, the patient is placed on a protocol testing novel combinations that do not contain a target-specific drug.~TREATMENT: Patients are assigned to a specific treatment protocol.~MM1YA-CTG01: Younger patients (age 18-59 years) with intermediate risk acute myeloid leukemia (AML) are randomized to 1 of 3 arms.~ARM I: Patients receive daunorubicin intravenously (IV), cytarabine IV, and venetoclax orally (PO) on study and undergo bone marrow aspiration and collection of blood samples on study and as clinically indicated.~ARM II: Patients receive azacitidine IV or subcutaneously (SC) and venetoclax PO on study and undergo bone marrow aspiration and collection of blood samples on study and as clinically indicated.~ARM III: Patients receive daunorubicin IV and cytarabine IV on study and undergo bone marrow aspiration and collection of blood samples on study and as clinically indicated.~MM1YA-S01: Younger patients (age 18-59 years) with high-risk AML are randomized to 1 of 4 arms.~ARM I: Patients receive cytarabine IV and daunorubicin IV per standard approach on study. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial.~ARM II: Patients receive cytarabine IV and daunorubicin IV with venetoclax PO on study. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial.~ARM III: Patients receive azacitidine SC or IV and venetoclax PO on study. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial.~ARM IV: Patients receive daunorubicin and cytarabine liposome (Vyxeos) IV on study. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial.~MM2YA-EA01: Younger patients (age 18-59 years) with AML or secondary AML who have completed a tier 1 MyeloMATCH treatment study with complete remission (CR) or CR with partial hematologic recovery (CRh) and have detectable minimal residual disease (MRD) (> 0.1%) are randomized to 1 of 4 arms.~ARM A: Patients receive cytarabine IV on study. Patients undergo bone marrow aspiration and biopsy on study. Patients may also undergo echocardiogram (ECHO) and/or multigated acquisition scan (MUGA) as clinically indicated.~ARM B: Patients receive cytarabine IV and venetoclax PO on study. Patients undergo bone marrow aspiration and biopsy on study. Patients may also undergo ECHO and/or MUGA as clinically indicated.~ARM C: Patients receive Vyxeos IV and venetoclax PO on study. Patients undergo bone marrow aspiration and biopsy on study. Patients may also undergo ECHO and/or MUGA as clinically indicated.~ARM D: Patients receive azacitidine IV or SC and venetoclax PO on study. Patients undergo bone marrow aspiration and biopsy on study. Patients may also undergo ECHO and/or MUGA as clinically indicated.
This MyeloMATCH Master Screening and Reassessment Protocol (MSRP) evaluates the use of a screening tool and specific laboratory tests to help improve participants' ability to register to clinical trials throughout the course of their myeloid cancer (acute myeloid leukemia or myelodysplastic syndrome) treatment. This study involves testing patients' bone marrow and blood for certain biomarkers. A biomarker (sometimes called a marker) is any molecule in the body that can be measured. Doctors look at markers to learn what is happening in the body. Knowing about certain markers can give doctors more information about what is driving the cancer and how to treat it. Testing patients' bone marrow and blood will show doctors if patients have markers that specific drugs can target. The marker testing in this study will let doctors know if they can match patients with a treatment study (myeloMATCH clinical trial) that tests treatment for the type of cancer they have.