Health TrialsbyHealthPanel

Luspatercept + Darbepoetin in MDS

ConditionMDS (Myelodysplastic Syndrome)
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorYale University

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Single group

Treatments tested in this trial

  • 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.

  • 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.

Treatment groups

60 Participants
are divided into 1 treatment group
Group A: Luspatercept + DarbepoetinExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

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

Time frame
24 weeks
2

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.

Time frame
24 weeks

Secondary outcomes

1

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

Mean rate of red blood cell transfusion independence (RBC-TI) for at least 8 consecutive weeks during weeks 1-24 compared to baseline. Assessed as the proportion of participants who achieve RBC-TI within the first 24 weeks of the study.

Time frame
24 weeks
2

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

Mean rate of red blood cell transfusion independence (RBC-TI) for at least 8 consecutive weeks during weeks 1-48 compared to baseline. Assessed as the proportion of participants who achieve RBC-TI within the first 48 weeks of the study.

Time frame
48 weeks
3

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

Mean rate of red blood cell transfusion independence (RBC-TI) for at least 12 consecutive weeks during weeks 1-24 compared to baseline. Assessed as the proportion of participants who achieve RBC-TI within the first 24 weeks of the study.

Time frame
24 weeks
4

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

Mean rate of red blood cell transfusion independence (RBC-TI) for at least 12 consecutive weeks during weeks 1-48 compared to baseline. Assessed as the proportion of participants who achieve RBC-TI within the first 48 weeks of the study.

Time frame
48 weeks

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Yale University

Lead sponsor

Bristol-Myers Squibb

Collaborator

Source ClinicalTrials.gov
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