MYELOMATCH: A Screening Study to Assign People With Myeloid Cancer to a Treatment Study or Standard of Care Treatment Within myeloMATCH (MyeloMATCH Screening Trial)

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05564390
• Other study ID #: NCI-2022-07006
• Secondary ID: NCI-2022-07006MY
• Status: Recruiting
• Phase: Phase 2
• Start date: June 18, 2024
• Est. completion date: May 15, 2029

Study information

• Verified date: June 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 or continue standard of care treatment with their doctor on the Tier Advancement Pathway (TAP).

Description:

PRIMARY OBJECTIVES:

I. Screening and Reassessment (MSRP): To evaluate the feasibility of MATCHBox receiving and organizing all data needed for assignment to a myeloMATCH clinical trial or Tier Advancement Pathway (TAP) within 72 hours of MDNet receipt of all required specimens for initial therapy and within 10 days for subsequent therapy.

II. Tier Advancement Pathway (TAP): To enable participants who are not matched to an investigational myeloMATCH treatment substudy to receive standard of care (SOC) while remaining on the MSRP to maintain access to later tiers of treatment substudies.

SECONDARY OBJECTIVES:

I. Screening and Reassessment (MSRP):

Ia. To describe the time to generation of all data required for treatment substudy (or TAP) assignment, time to treatment substudy (or TAP) assignment, percent assigned to a myeloMATCH treatment substudy, and the percent of screened participants who register to a myeloMATCH investigational treatment substudy or are assigned to TAP:

Iai. Separately within each tier of myeloMATCH treatment substudy and analogous TAP assignment; Ibi. Separately within each clinical basket of myeloMATCH treatment substudies; Ici. Over time, across and within the categories above.

II. Tier Advancement Pathway (TAP):

IIa. To evaluate participants for assignment to higher tier treatment substudies within myeloMATCH; IIb. To describe, within tier- and basket- levels of TAP, measurable residual disease (MRD) rates and clonal evolution; IIc. To describe, within tier- and basket- levels of TAP, remission status and overall survival of participants who receive standard of care therapy; IId. To obtain MDNet specimens for translational medicine and biobanking.

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 substudy containing a therapy targeted to the patient's mutational profile. If there is no targetable mutation, the patient is placed on a substudy testing novel combinations that do not contain a target-specific drug. Patients who are not eligible for any MYELOMATCH substudy are assigned to TAP.

TAP: Patients continue SOC treatment and undergo continued bone marrow aspiration and blood collection for possible future substudy assignment.

TREATMENT: Patients are assigned to a specific treatment substudy.

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 5 arms.

ARM I: Patients receive cytarabine IV continuously on days 1-7 and daunorubicin IV on days 1-3 per standard approach of each cycle. Cycles repeat every 28 days for 1 cycle in the absence of disease progression or unacceptable toxicity. Patients may receive an additional cycle of cytarabine IV continuously on days 1-5 and daunorubicin IV on days 1-2. Patients undergo echocardiography (ECHO) or multigated acquisition (MUGA) scan during screening. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial.

ARM II: Patients receive cytarabine IV continuously on days 2-8 and daunorubicin IV on days 2-4 with venetoclax PO on days 1-11 of each cycle. Cycles repeat every 28 days for 1 cycle in the absence of disease progression or unacceptable toxicity. Patients may receive an additional cycle of cytarabine IV continuously on days 2-6 and daunorubicin IV on days 2-3 with venetoclax PO on days 1-8. Patients undergo ECHO or MUGA scan during screening. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial.

ARM III: Patients receive azacitidine SC or IV on days 1-7 and venetoclax PO on days 1-28 of each cycle. Cycles repeat every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA scan during screening. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial.

ARM IV: Patients receive daunorubicin and cytarabine liposome IV over 90 minutes on days 1, 3, and 5 of each cycle. Cycles repeat every 28 days for 1 cycle in the absence of disease progression or unacceptable toxicity. Patients may receive an additional cycle of daunorubicin and cytarabine liposome IV over 90 minutes on days 1 and 3. Patients undergo ECHO or MUGA scan during screening. 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 ECHO and/or 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.

MM1OA-EA02: Patients are randomized to 1 of 3 regimens.

REGIMEN 1:

INDUCTION: Patients receive azacitidine IV or SC on days 1-7 and venetoclax PO on days 1-28 of each cycle. Treatment repeats every 28 days for up to 2 cycles or until patient achieves remission, whichever comes first, in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Patients receive azacitidine IV or SC on days 1-7 and venetoclax PO on days 1-28 of each cycle. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.

REGIMEN 2:

INDUCTION: Patients receive azacitidine IV or SC on days 1-7 and venetoclax and gilteritinib PO on days 1-28 of each cycle. Treatment repeats every 28 days for up to 2 cycles or until patient achieves remission, whichever comes first, in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Patients receive azacitidine IV or SC on days 1-5, venetoclax PO on days 1-7 and gilteritinib PO on days 1-28 of each cycle. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.

REGIMEN 3:

INDUCTION: Patients receive azacitidine IV or SC on days 1-7 and venetoclax PO on days 1-28, and gilteritinib PO on days 8-21 of each cycle. Treatment repeats every 28 days for up to 2 cycles or until patient achieves remission, whichever comes first, in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Patients receive azacitidine IV or SC on days 1-5, venetoclax PO on days 1-14 and gilteritinib PO on days 8-21 of each cycle. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.

All patients undergo bone marrow biopsy and aspiration as well as blood sample collection on the trial.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: May 15, 2029
• Est. primary completion date: May 15, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participants must be suspected to have previously untreated acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Participants with AML cannot have a history of previously treated myeloproliferative neoplasms (MPN) or MDS.

• Participants must be >= 18 years of age.

• 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.

• Note: Prior erythroid stimulating agent (ESA) is not considered prior therapy for the purposes of eligibility. Participants must not be currently receiving any cytarabine-containing therapy other than up to 1 g/m^2 of cytarabine, which is allowed for urgent cytoreduction.

• Participants are allowed prior use of hydroxyurea, all-trans retinoic acid (ATRA), BCR-ABL directed tyrosine kinase inhibitor, erythropoiesis-stimulating agent, thrombopoietin receptor agonist and lenalidomide, with a maximum limit of 1 month of exposure.

• Note: Participants receiving hydroxyurea prior to treatment substudy or TAP assignment must agree to discontinue hydroxyurea within 24 hours before beginning substudy or TAP treatment.

• Participants must not have a prior or concurrent malignancy that requires concurrent anti-cancer therapy

• Note: active hormonal therapy is allowed

• Participants must have a Zubrod Performance Status evaluation within 28 days prior to registration.

• Participants must agree to have translational medicine specimens submitted.

• Participants must be offered the opportunity to participate in specimen banking.

• Note: Specimens must be collected and submitted following the initial paper-based process and subsequently via the Precision Medicine Specimen Tracking Forms in Medidata Rave instance for the MyeloMATCH MSRP.

• 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) should only be used in sites where the relevant AML treatment substudies are open or if the site is willing to follow the MSRP Tier Advancement Pathway (TAP) for patients in the event that the site does not have the relevant study open and transfer to another site that does have the study 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 only be consented for the MSRP if the site is willing to treat the patient with standard of care on TAP or is willing to transfer the patient to a center with a study open that the patient would otherwise match to.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes

Intervention

Drug:
• Azacitidine
Given IV or SC

Other:
• Best Practice
Receive SOC treatment

Procedure:
• Biopsy
Undergo biopsy
• Biospecimen Collection
Undergo collection of blood samples
• Bone Marrow Aspiration
Undergo bone marrow aspiration

Drug:
• Cytarabine
Given
• Daunorubicin Hydrochloride
Given IV

Procedure:
• Echocardiography
Undergo ECHO

Drug:
• Gilteritinib
Given PO
• Liposome-encapsulated Daunorubicin-Cytarabine
Given IV

Procedure:
• Multigated Acquisition Scan
Undergo MUGA
• Mutation Carrier Screening
Undergo rapid genetic testing

Drug:
• Venetoclax
Given PO

Locations

Country	Name	City	State
Puerto Rico	Centro Comprensivo de Cancer de UPR	San Juan
Puerto Rico	San Juan City Hospital	San Juan
United States	Trinity Health Saint Joseph Mercy Hospital Ann Arbor	Ann Arbor	Michigan
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	OSF Saint Joseph Medical Center	Bloomington	Illinois
United States	Trinity Health IHA Medical Group Hematology Oncology - Brighton	Brighton	Michigan
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Trinity Health IHA Medical Group Hematology Oncology - Canton	Canton	Michigan
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital	Chelsea	Michigan
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	Illinois CancerCare-Dixon	Dixon	Illinois
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Genesee Cancer and Blood Disease Treatment Center	Flint	Michigan
United States	Genesee Hematology Oncology PC	Flint	Michigan
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Siteman Cancer Center at Christian Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Illinois CancerCare - Washington	Washington	Illinois
United States	Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Timing of treatment Substudy or Tier Advancement Pathway (TAP) 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 needed 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	Time to MDNet generating all data required for treatment substudy or TAP assignment	Will be assessed within each tier of clinical trials, within each clinical basket of clinical trials, and over time (since last report and in 6 month intervals from study opening).	Within 72 hours of MDNet receipt of specimens for initial therapy or within 10 days for subsequent therapy
Secondary	Time to treatment substudy or TAP assignment	Will be assessed within each tier of clinical trials, within each clinical basket of clinical trials, and over time (since last report and in 6 month intervals from study opening).	Within 72 hours of MDNet receipt of specimens for initial therapy or within 10 days for subsequent therapy
Secondary	Percent assigned to a myeloMATCH clinical trial	Will be assessed within each tier of clinical trials, within each clinical basket of clinical trials, and over time (since last report and in 6 month intervals from study opening).	Within 72 hours of MDNet receipt of specimens for initial therapy or within 10 days for subsequent therapy
Secondary	Percent of screened participants who register to a treatment substudy	Will be assessed within each tier of clinical trials, within each clinical basket of clinical trials, and over time (since last report and in 6 month intervals from study opening).	Within 72 hours of MDNet receipt of specimens for initial therapy or within 10 days for subsequent therapy
Secondary	Assignment to higher tier treatment substudies within myeloMATCH	Will be assessed within each tier of clinical trials, within each clinical basket of clinical trials, and over time (since last report and in 6 month intervals from study opening).	Within 72 hours of MDNet receipt of specimens for initial therapy or within 10 days for subsequent therapy
Secondary	Adverse events	Will be assessed within each tier of clinical trials, within each clinical basket of clinical trials, and over time (since last report and in 6 month intervals from study opening).	Within 72 hours of MDNet receipt of specimens for initial therapy or within 10 days for subsequent therapy
Secondary	Minimal residual disease (MRD) response	MRD response is based on flow cytometry studies performed by the MDnet.	Within 72 hours of MDNet receipt of specimens for initial therapy or within 10 days for subsequent therapy
Secondary	Time-to-event outcomes for exploratory analysis	Will be assessed within each tier of clinical trials, within each clinical basket of clinical trials, and over time (since last report and in 6 month intervals from study opening).	Within 72 hours of MDNet receipt of specimens for initial therapy or within 10 days for subsequent therapy
Secondary	Performance status	Participants will be graded according to the Zubrod performance status scale.	Within 72 hours of MDNet receipt of specimens for initial therapy or within 10 days for subsequent therapy