MyeloMATCH MSRP: A Screening Study to Assign People With Myeloid Cancer to a Treatment Study

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

Official Title
-----------------
Master Screening and Reassessment Protocol (MSRP) for the NCI MyeloMATCH Clinical Trials

Conditions
-----------------
Acute Myeloid Leukemia, Myelodysplastic Syndrome

Intervention / Treatment
-----------------
* Drug: Azacitidine
* Procedure: Biospecimen Collection
* Procedure: Bone Marrow Aspiration
* Procedure: Bone Marrow Aspiration and Biopsy
* Drug: Cytarabine
* Drug: Daunorubicin Hydrochloride
* Procedure: Echocardiography
* Drug: Liposome-encapsulated Daunorubicin-Cytarabine
* Procedure: Multigated Acquisition Scan
* Procedure: Mutation Carrier Screening
* Drug: Venetoclax


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants must be suspected to have previously untreated acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). For participants assigned an AML basket protocol, there cannot be a history of previous myeloproliferative neoplasm (MPN) or MDS. Participants must be >= 18 years of age. Participants must agree to have specimens submitted. Note: Email notification of treatment protocol assignment must be received prior to treatment protocol registration. Participants must be offered the opportunity to participate in specimen banking. Note: With participant consent, specimens must be collected and submitted via the Clinical/Correlative Sample Management System (CSMS). Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines. Note: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system. The Master Screening and Reassessment Protocol (MSRP) is only used in sites where the relevant AML clinical trials are open. For example, if a site does not have a myeloMATCH tier 1 study for older AML open for enrollment, such older AML patients should not be consented for the MSRP Exclusion Criteria: Participants must not have received prior anti-cancer therapy for AML or MDS. Note: Hydroxyurea to control the white blood cell count (WBC) is allowed. Participants must not have a prior or concurrent malignancy that requires concurrent anti-cancer therapy Note: active hormonal therapy is allowed

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MM1YA-CTG01 Arm I (daunorubicin, cytarabine, venetoclax)<br>Patients receive daunorubicin IV, cytarabine IV, and venetoclax PO on study and undergo bone marrow aspiration and collection of blood samples on study and as clinically indicated. | Procedure: Biospecimen Collection<br>* Undergo collection of blood samples<br>* Other names: Specimen Collection;Procedure: Bone Marrow Aspiration<br>* Undergo bone marrow aspiration<br>Drug: Cytarabine<br>* Given<br>* Other names: WR-28453;Drug: Daunorubicin Hydrochloride<br>* Given IV<br>* Other names: Rubilem;Drug: Venetoclax<br>* Given PO<br>* Other names: Venclyxto;|
| Experimental: MM1YA-CTG01 Arm II (azacitidine, venetoclax)<br>Patients receive azacitidine IV or SC and venetoclax PO on study and undergo bone marrow aspiration and collection of blood samples on study and as clinically indicated. | Drug: Azacitidine<br>* Given IV or SC<br>* Other names: Vidaza;Procedure: Biospecimen Collection<br>* Undergo collection of blood samples<br>* Other names: Specimen Collection;Procedure: Bone Marrow Aspiration<br>* Undergo bone marrow aspiration<br>Drug: Venetoclax<br>* Given PO<br>* Other names: Venclyxto;|
| Active Comparator: MM1YA-CTG01 Arm III (daunorubicin, cytarabine)<br>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. | Procedure: Biospecimen Collection<br>* Undergo collection of blood samples<br>* Other names: Specimen Collection;Procedure: Bone Marrow Aspiration<br>* Undergo bone marrow aspiration<br>Drug: Cytarabine<br>* Given<br>* Other names: WR-28453;Drug: Daunorubicin Hydrochloride<br>* Given IV<br>* Other names: Rubilem;|
| Active Comparator: MM1YA-S01 Arm I (cytarabine, daunorubicin)<br>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. | Procedure: Biospecimen Collection<br>* Undergo collection of blood samples<br>* Other names: Specimen Collection;Procedure: Bone Marrow Aspiration<br>* Undergo bone marrow aspiration<br>Drug: Cytarabine<br>* Given<br>* Other names: WR-28453;Drug: Daunorubicin Hydrochloride<br>* Given IV<br>* Other names: Rubilem;|
| Experimental: MM1YA-S01 Arm II (cytarabine, daunorubicin, venetoclax)<br>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. | Procedure: Biospecimen Collection<br>* Undergo collection of blood samples<br>* Other names: Specimen Collection;Procedure: Bone Marrow Aspiration<br>* Undergo bone marrow aspiration<br>Drug: Cytarabine<br>* Given<br>* Other names: WR-28453;Drug: Daunorubicin Hydrochloride<br>* Given IV<br>* Other names: Rubilem;Drug: Venetoclax<br>* Given PO<br>* Other names: Venclyxto;|
| Experimental: MM1YA-S01 Arm III (azacitidine, venetoclax)<br>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. | Drug: Azacitidine<br>* Given IV or SC<br>* Other names: Vidaza;Procedure: Biospecimen Collection<br>* Undergo collection of blood samples<br>* Other names: Specimen Collection;Procedure: Bone Marrow Aspiration<br>* Undergo bone marrow aspiration<br>Drug: Venetoclax<br>* Given PO<br>* Other names: Venclyxto;|
| Experimental: MM1YA-S01 Arm IV (Vyxeos)<br>Patients receive Vyxeos IV on study. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial. | Procedure: Biospecimen Collection<br>* Undergo collection of blood samples<br>* Other names: Specimen Collection;Procedure: Bone Marrow Aspiration<br>* Undergo bone marrow aspiration<br>Drug: Liposome-encapsulated Daunorubicin-Cytarabine<br>* Given IV<br>* Other names: Vyxeos;|
| Active Comparator: MM2YA-EA01 Arm A (cytarabine)<br>Patients receive cytarabine IV on study. Patients undergo bone marrow aspiration and biopsy on study. Patients may also undergo ECHO and/or MUGA as clinically indicated. | Procedure: Bone Marrow Aspiration and Biopsy<br>* Undergo bone marrow aspiration and biopsy<br>Drug: Cytarabine<br>* Given<br>* Other names: WR-28453;Procedure: Echocardiography<br>* Undergo ECHO<br>* Other names: EC;Procedure: Multigated Acquisition Scan<br>* Undergo MUGA<br>* Other names: Synchronized Multigated Acquisition Scanning;|
| Experimental: MM2YA-EA01 Arm B (cytarabine, venetoclax)<br>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. | Procedure: Bone Marrow Aspiration and Biopsy<br>* Undergo bone marrow aspiration and biopsy<br>Drug: Cytarabine<br>* Given<br>* Other names: WR-28453;Procedure: Echocardiography<br>* Undergo ECHO<br>* Other names: EC;Procedure: Multigated Acquisition Scan<br>* Undergo MUGA<br>* Other names: Synchronized Multigated Acquisition Scanning;Drug: Venetoclax<br>* Given PO<br>* Other names: Venclyxto;|
| Experimental: MM2YA-EA01 Arm C (Vyxeos, venetoclax)<br>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. | Procedure: Bone Marrow Aspiration and Biopsy<br>* Undergo bone marrow aspiration and biopsy<br>Procedure: Echocardiography<br>* Undergo ECHO<br>* Other names: EC;Drug: Liposome-encapsulated Daunorubicin-Cytarabine<br>* Given IV<br>* Other names: Vyxeos;Procedure: Multigated Acquisition Scan<br>* Undergo MUGA<br>* Other names: Synchronized Multigated Acquisition Scanning;Drug: Venetoclax<br>* Given PO<br>* Other names: Venclyxto;|
| Experimental: MM2YA-EA01 Arm D (azacitidine, venetoclax)<br>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. | Drug: Azacitidine<br>* Given IV or SC<br>* Other names: Vidaza;Procedure: Bone Marrow Aspiration and Biopsy<br>* Undergo bone marrow aspiration and biopsy<br>Procedure: Echocardiography<br>* Undergo ECHO<br>* Other names: EC;Procedure: Multigated Acquisition Scan<br>* Undergo MUGA<br>* Other names: Synchronized Multigated Acquisition Scanning;Drug: Venetoclax<br>* Given PO<br>* Other names: Venclyxto;|
| Experimental: Screening (mutation carrier screening)<br>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. | Procedure: Mutation Carrier Screening<br>* Undergo rapid genetic testing<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Timing of treatment assignment | Will 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. For first treatment assignment and separately for each subsequent treatment assignments: every 50 participants for the first 250 participants and then every 100 participants thereafter, the proportion of participants (cumulative and new participants since prior analysis) with all MDNet data need to determine a treatment assignment within 72 hours for first assignment and 10 days for subsequent assignments after the MDNet receives specimens will be tallied. | Within 72 hours of MDNet receipt of specimens for initial therapy or within 10 days for subsequent therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to MDNet generating all data required for treatment assignment | Will be assessed for the first (induction) treatment assignment, for post-induction treatment assignment, within each tier of clinical trials, within each clinical basket of clinical trials, and over time (since last report and in 6 months intervals). | Within 72 hours of MDNet receipt of specimens for initial therapy or within 10 days for subsequent therapy | 
| Time to treatment assignment | Will be assessed for the first (induction) treatment assignment, for post-induction treatment assignment, within each tier of clinical trials, within each clinical basket of clinical trials, and over time (since last report and in 6 months intervals). | Within 72 hours of MDNet receipt of specimens for initial therapy or within 10 days for subsequent therapy | 
| Percent assigned to a myeloMATCH clinical trial | Will be assessed for the first (induction) treatment assignment, for post-induction treatment assignment, within each tier of clinical trials, within each clinical basket of clinical trials, and over time (since last report and in 6 months intervals). | Within 72 hours of MDNet receipt of specimens for initial therapy or within 10 days for subsequent therapy | 
| Percent of screened participants who register to a protocol | Will be assessed for the first (induction) treatment assignment, for post-induction treatment assignment, within each tier of clinical trials, within each clinical basket of clinical trials, and over time (since last report and in 6 months intervals). | Within 72 hours of MDNet receipt of specimens for initial therapy or within 10 days for subsequent therapy |