A Trial Comparing Three Different Treatment Options for Adults With Low-Risk Myelodysplasia and Anemia (A MyeloMATCH Treatment Trial)

NCT07463820 | Not Yet Recruiting Phase 2 FDA Drug

• 3 other identifiers: NCI-2026-01399MM1MDS-CTG02U10CA180863
• Study Type: interventional
• Target: 270
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II MyeloMATCH treatment trial tests luspatercep with or without epoetin alfa or emavusertib for the treatment of low risk myelodysplasia and anemia. Biological therapies, such as luspatercep, use substances made from living organisms that may attack specific cancer cells and stop them from growing or kill them. Epoetin alfa is a substance that is made in the laboratory and stimulates the bone marrow to make red blood cells. Emavusertib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving luspatercep with or without epoetin alfa or emavusertib may be effective for treating patients with low risk myelodysplasia and anemia.

Conditions

Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Erythroid response rate

  Defined by the total number of patients with hematologic improvement-erythroid (HI-E) response divided by the total number of randomized patients in each arm. The comparison of the HI-E rate will be done using a Cochran-Mantel-Haenszel test stratified for the stratification factors at randomization based on the intent-to-treat population. The difference in the response rates and the corresponding one-sided 90% confidence limit will be calculated.

  At 24 weeks

Secondary Outcomes (7)

• Transfusion free survival

  Up to 2 years

• Duration of erythroid response

  From meeting criteria for HI-E response to progression or relapse as defined by IWG 2018 criteria, up to 2 years

• Tri-lineage response

  Up to 2 years

• Bi-lineage response

  Up to 2 years

• Incidence of adverse events

  From the time of first treatment, up to 2 years

Study Arms (3)

Arm 1 (Luspatercept)

EXPERIMENTAL

Patients receive luspatercept SC on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration and blood sample collection throughout the study.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Biological: Luspatercept

Arm 2 (Luspatercept with epoetin alfa)

EXPERIMENTAL

Patients receive luspatercept SC on day 1 and epoetin alfa SC QW for each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration and blood sample collection throughout the study.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Biological: Epoetin Alfa; Biological: Luspatercept

Arm 3 (Luspatercept and emavusertib)

EXPERIMENTAL

Patients receive luspatercept SC on day 1 and emavusertib PO BID on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration and blood sample collection throughout the study.

Procedure: Bone Marrow Aspiration; Biological: Emavusertib; Biological: Luspatercept

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Arm 1 (Luspatercept); Arm 2 (Luspatercept with epoetin alfa)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Arm 1 (Luspatercept); Arm 2 (Luspatercept with epoetin alfa); Arm 3 (Luspatercept and emavusertib)

Emavusertib BIOLOGICAL

Given PO

Also known as: AU 4948, AU-4948, CA 4948, CA-4948, CA4948, Interleukin-1 Receptor-associated Kinase 4 Inhibitor CA-4948, IRAK4 Inhibitor CA-4948

Arm 3 (Luspatercept and emavusertib)

Epoetin Alfa BIOLOGICAL

Given SC

Also known as: EPO, Epoetin alfa-epbx, Epogen, Eprex, Procrit, Retacrit

Arm 2 (Luspatercept with epoetin alfa)

Luspatercept BIOLOGICAL

Given SC

Also known as: ACE 536, ACE-536, ACE536, Luspatercept-aamt, Reblozyl

Arm 1 (Luspatercept); Arm 2 (Luspatercept with epoetin alfa); Arm 3 (Luspatercept and emavusertib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Participants must have pathologically confirmed MDS according to World Health Organization (WHO) 2022 classification, without excess blasts
• Lower risk MDS with a revised international prognostic scoring system (IPSS-R) score of less than or equal to 3.5
• Symptomatic anemia defined as either red blood cell (RBC) transfusion dependent, or hemoglobin \< 95 g/L with subjective fatigue or dyspnea
• Age 18 years or greater
• No prior therapy for myelodysplasia; including no luspatercept, imetelstat, emavusertib, lenalidomide, hypomethylating or immunosuppressive agents. Patients may have received up to 2 prior doses of erythropoietin stimulating agents (epoetin alfa or darbepoetin) if at least 8 weeks have elapsed between the prior therapy and study enrollment
• No concurrent radiotherapy, biological, or any other investigational agents within 30 days prior to enrollment
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
• Absolute neutrophil count ≥ 0.5 x 10\^9/L
• Platelet count ≥ 50 x 10\^9/L
• Bilirubin ≤ 3.0 x upper limit of normal (ULN)
• If confirmed Gilbert's, eligible providing direct bilirubin ≤ 3.0 x ULN
• Alanine aminotransferase (ALT) ≤ 3.0 x ULN
• Erythropoeitin ≤ 500 IU/L
• Creatinine clearance \> 30 mL/min

You may not qualify if:

• Participants 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
• MDS with del(5q)
• Concurrent use of hematopoietic growth factors (other than protocol specified)
• Known hypersensitivity to either luspatercept, erythropoietin, or emavusertib therapy
• Participants who are unable to take oral medication regularly, with active gastroparesis, short gut syndrome, or other malabsorption syndrome
• Active, uncontrolled bacterial, fungal, or viral infection within 14 days prior to enrollment.
• Participants with hepatitis B core antibody positive suggestive of past infection are eligible if they are hepatitis B virus (HBV) deoxyribonucleic acid (DNA) negative and concurrently treated with anti-viral therapy. Participants who are hepatitis B surface antigen positive should be referred for appropriate care and considered eligible if hepatitis B DNA becomes negative.
• Participants with a history of hepatitis C which has been treated and is no longer active are eligible. Patients who have not been treated should be referred for appropriate care.
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• Participants on prophylactic antimicrobials need not be excluded, although specific agents may be excluded for drug-to-drug interactions or overlapping toxicities.
• Participants who do not meet these eligibility criteria should be referred for appropriate care and may be considered in the future if eligibility criteria are met
• Participants with serious illnesses or medical conditions which would not permit the participant to be managed according to protocol including but not limited to:
• Uncontrolled hypertension, defined as repeated systolic blood pressure greater than 160 and/or diastolic greater than 100 mmHg despite adequate treatments,
• 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 II or better
• Iron deficiency defined as ferritin of \< 50 ug/L

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Specimen Handling; CA-4948; Epoetin Alfa; luspatercept

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Rena J Buckstein

  Canadian Cancer Trials Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2026
• First Posted: March 11, 2026
• Study Start (Estimated): June 19, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: May 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share