Luspatercept + Darbepoetin in MDS

NCT07096297 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2000039532
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

Brief Summary

This is a single arm open-label Phase II trial of luspatercept and darbepoetin alfa in non-mutated SF3B1 , lower-risk, RBC transfusion dependent MDS participants with an endogenous erythropoietin (EPO) level \< 500 IU/L.

Conditions

MDS (Myelodysplastic Syndrome)

Keywords

SF3B1 wild type; RBC transfusion dependent; lower risk; non-mutated SF3B1

Outcome Measures

Primary Outcomes (2)

• Mean Rate of Red Blood Cell Transfusion Independence

  Mean rate of red blood cell transfusion independence (RBC-TI) for at least any consecutive 84 days (≥ 12 consecutive weeks) during weeks 1-24 compared to baseline in non-mutated SF3B1, lower-risk myelodysplastic syndrome patients treated with Luspatercept plus Darbepoetin Alfa

  24 weeks

• Mean Rate of Hemoglobin Increase

  Mean rate of hemoglobin ≥ 1.5 g/dL during weeks 1-24 compared to baseline in non-mutated SF3B1, lower-risk myelodysplastic syndrome patients treated with Luspatercept plus Darbepoetin Alfa.

  24 weeks

Secondary Outcomes (16)

• Mean rate of Red Blood Cell Transfusion Independence for ≥8 Consecutive Weeks During Weeks 1-24

  24 weeks

• Mean rate of Red Blood Cell Transfusion Independence for ≥8 Consecutive Weeks During Weeks 1-48

  48 weeks

• Mean rate of Red Blood Cell Transfusion Independence for ≥12 Consecutive Weeks During Weeks 1-24

  24 weeks

• Mean rate of Red Blood Cell Transfusion Independence for ≥12 Consecutive Weeks During Weeks 1-48

  48 weeks

• Mean rate of Red Blood Cell Transfusion Independence for ≥24 Consecutive Weeks During Weeks 1-24

  24 weeks

Study Arms (1)

Luspatercept + Darbepoetin

EXPERIMENTAL

Each participant will be treated with luspatercept every 21 days (three weeks) in combination with darbepoetin alfa every 21 days (three weeks). Both agents will be administered on day 1 of each 21-day cycle. Based on the individual participant's response to combination therapy of luspatercept and darbepoetin alfa, the doses of luspatercept and/or darbepoetin alfa can be either decreased or increased. The starting dose is luspatercept at 1.0 mg/kg (Dose Level 0) and darbepoetin alfa 300 µg (Dose Level 0).

Drug: Luspatercept; Drug: Darbeopoetin

Interventions

Luspatercept DRUG

Luspatercept will be administered every 3 weeks (21 days) at a starting dose of 1.0 mg/kg (Dose Level 0). Luspatercept will be administered to participants by the study staff at the clinical site and administration will be documented in the participant's source record. Participants must have Hgb, blood pressure and weight assessed (changes of body weight of ≤ ± 5% do not require a dose adjustment) prior to each luspatercept dose administration. Subcutaneous injections will be given in the upper arm, thigh, and/or abdomen. Volume for subcutaneous injection will be per institutional standard/guidelines.

Luspatercept + Darbepoetin

Darbeopoetin DRUG

Darbepoetin alfa will be administered every 3 weeks (21 days), at a starting dose of 300 ug (Dose Level 0). Darbepoetin alfa will be administered to participants by the study staff at the clinical site and administration will be documented in the participant's source record. Darbepoetin alfa will be administered as a subcutaneous injection by the site staff in the upper arm, thigh, and/or abdomen per institutional standard/guidelines.

Luspatercept + Darbepoetin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent document.
• Participant is 18 years or older at the time of signing informed consent.
• Participant has lower-risk myelodysplastic syndrome (MDS) defined as very low, low and intermediate risk by International Prognostic Scoring System-Revised (IPSS-R) criteria (3).
• Bone marrow biopsy within 90 days of screening demonstrated less than 5% blasts in the aspirate and/or core biopsy. If no bone marrow biopsy was done within 90 days of screening it is mandatory to repeat it at screening. Otherwise, bone marrow biopsy is optional at screening to obtain correlative study samples.
• Absence of SF3B1 mutation and del5q.
• Endogenous serum erythropoietin alfa (EPO) level \< 500 IU/L.
• Participant is transfusion dependent defined as ≥ 2 packed red blood cell (PRBC) units/8 weeks for a minimum of eight weeks immediately prior to screening. The maximum consecutive timeframe participants may be RBC transfusion-free within this 8-week time period is six weeks.
• a. Red blood cell transfusions administered when hemoglobin levels were \> 9.0 g/dL and/or RBC transfusions administered for elective surgery, infections or bleeding events will not be counted in above.
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3 (Appendix 1. ECOG Performance Status Scale).
• Participant has adequate organ function defined as:
• Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 3 x ULN, unless considered due to organ involvement by the participant's myeloid malignancy (in that case a cut off ≤ 5 x ULN will be used).
• Serum direct bilirubin \< 1.5 x ULN.
• Creatinine clearance \> 30 mL/min based on the Cockroft-Gault glomerular filtration rate (GFR) estimation.
• Participants must adhere to the following reproductive and contraceptive requirements while on study treatment and for three months after the last dose of luspatercept and darbepoetin alfa:
• a. General Requirements: i. Participants must not be pregnant or breastfeeding. ii. Participants must not donate gametes (i.e., eggs or sperm) or freeze gametes for future use related to assisted reproduction.

You may not qualify if:

• Prior treatment with ESA, luspatercept, hypomethylating agents or lenalidomide/thalidomide/other immunomodulating drug (IMiDs).
• Exception 1: Participants can have received ≤ 2 doses of prior epoetin alfa or ≤ 1 dose darbepoetin alfa if ≥ 8 weeks from date of consent.
• Exception 2: Participants can have received ≤ 1 week of treatment with lenalidomide ≥ 8 weeks from the date of consent, at the sponsor-investigator's discretion.
• After signing consent, the participants are not allowed to receive any of these drugs: other RBC hematopoietic growth factors (e.g., Interleukin-3), granulocyte colony stimulating factors (i.e., G-CSF, GM-CSF), except in cases of neutropenic fever, cytotoxic, chemotherapeutic, targeted or investigational agents/therapies, azacitidine, decitabine or other hypomethylating agents, lenalidomide, thalidomide and other immunomodulating drugs (IMiDs), hydroxyurea, androgens, unless to treat hypogonadism, oral retinoids (topical retinoids are permitted), arsenic trioxide, interferon and interleukins.
• Participants with history of seizures at any time.
• Participants with any of the following conditions within six months prior to screening:
• Stroke.
• Thrombosis/thromboembolism.
• Myocardial infarction.
• Uncontrolled angina.
• Acute decompensated cardiac failure or New York Heart Association (NYHA) Class III-IV heart failure.
• Uncontrolled cardiac arrhythmia as determined by the investigator.
• Participant has immediate life-threatening, severe complications of their myeloid malignancy such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.
• Participants with uncontrolled hypertension defined as systolic blood pressure (SBP) of ≥ 150 mmHg and/or diastolic blood pressure (DBP) ≥ 100 mmHg despite adequate treatment. Participant with history of cerebrovascular accident (including ischemic, embolic, and hemorrhagic cerebrovascular accident), transient ischemic attack.
• Participant has active viral infection with human immunodeficiency virus (HIV), or active infection with hepatitis B virus (HBV) or active infection with hepatitis C virus (HCV). Participants with HIV that is controlled (not detectable viral load) with highly active antiretroviral therapy (HAART) are eligible to participate.

Sponsors & Collaborators

• Yale University: lead
• Bristol-Myers Squibb: collaborator

Study Sites (3)

Yale University

New Haven, Connecticut, 06510, United States

RECRUITING

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois, 60611, United States

NOT YET RECRUITING

Harold C. Simmons Comprehensive Cancer Center of UT Southwestern

Dallas, Texas, 75235, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Anemia, Refractory, with Excess of Blasts

Interventions

luspatercept

Condition Hierarchy (Ancestors)

Anemia, Refractory; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases

Study Officials

• Maximilian Stahl, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephanie Ladd

CONTACT

9548950576; stephanie.ladd@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: July 20, 2025
• First Posted: July 31, 2025
• Study Start: December 16, 2025
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): August 1, 2030
• Last Updated: March 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)