Luspatercept and Lenalidomide (L2) in Lower-risk, Non-del(5q) MDS Patients

NCT04539236 | Suspended Phase 1 DMC FDA Drug

• 2 other identifiers: 20201503CASE2920
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to evaluate if the combination of drugs, Lenalidomide and Luspatercept, will help improve the treatment of anemia in patients with lower-risk Myelodysplastic Syndrome (MDS).

Conditions

Myelodysplastic Syndromes

Keywords

non-del(5q) MDS

Outcome Measures

Primary Outcomes (4)

• MTD/RP2D of Luspatercept combined with Lenalidomide

  Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of Luspatercept combined with Lenalidomide (reported in mg/kg) from Phase Ib portion of study

  Up to 15 weeks

• DLT Rate for Phase Ib

  DLT rate is defined as the percentage of participants with Dose Limiting Toxicities (DLT) as evaluated by treating physician using the National Cancer Center (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. DLTs are non-hematologic events grade 3 or higher that are at least possibly related to the investigational product and do not resolve to grade 1 or lower within 21 days.

  Up to 15 weeks

• Percentage of participants with RBC-TI response

  Red Blood Cell Transfusion Independence (RBC-TI) response is defined as participants who are RBC transfusion free over any consecutive 56-day period

  Up to 5 years

• Toxicity Rate for Phase II

  Toxicity rate is defined as the percentage of participants with treatment emergent adverse events (TE-AEs) as evaluated by treating physician using the National Cancer Center (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  Up to 5 years

Secondary Outcomes (8)

• Percentage of participants with relevant reduction in RBC transfusion requirement

  Up to 5 years

• Percentage of participants with Erythroid Response

  Up to 5 years

• Duration of RBC-TI

  Up to 5 years

• Percentage of participants with Platelet Response

  Up to 5 years

• Percentage of participants with Neutrophil Response

  Up to 5 years

Study Arms (1)

Luspatercept + Lenalidomide Group

EXPERIMENTAL

Phase 1B: Luspatercept will be administered at starting dose 1.0 mg/kg and can be titrated to 1.33 and 1.75 mg/kg dependent on participant response. Lenalidomide will be administered in a dose escalation design between 3 cohorts to determine MTD (2.5 mg, 5 mg and 10 mg daily dose on a 21-day cycle). MTD will be defined as the dose level with 0 or 1 DLT out of 6 participants. MTD will be declared as the RP2D for the Phase II portion of the study. Phase II: Luspatercept will be administered at 1.0 mg/kg and can be titrated to 1.33 and 1.75 mg/kg dependent on participant response. Lenalidomide will be administered with the RP2D daily for 21 days on a 21 day cycle. Treatment with combination of Lenalidomide and Luspatercept will continue as long as a participant is deriving clinical benefit, in the opinion of the treating physician, for up to 5 years or until disease progression or treatment intolerance.

Drug: Lenalidomide; Drug: Luspatercept

Interventions

Lenalidomide DRUG

Administered daily by mouth on a 21 day cycle. Doses will be administered at 2.5 mg, 5 mg and 10 mg.

Also known as: Revlimid

Luspatercept + Lenalidomide Group

Luspatercept DRUG

Administered subcutaneously in the upper arm, thigh and/or abdomen on Day 1 of a 21 day cycle. Starting dose will be at 1.0 mg/kg and can be titrated, dependent on participant response, to doses of 1.33 mg/kg, and 1.75 mg/kg.

Also known as: Reblozyl, ActRIIB-IgG, ACE-536, 1373715-00-4

Luspatercept + Lenalidomide Group

Eligibility Criteria

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

You may qualify if:

• Subject is ≥ 18 years of age the time of signing the informed consent form (ICF).
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Documented diagnosis of MDS according to World Health Organization (WHO) / French-American-British (FAB) classification that meets International Prognostic Scoring System Revised (IPSS-R) classification (Greenberg, 2012) of very low, low, or intermediate risk disease; intermediate patients must have a blast percentage \<5% to be enrolled.
• Subjects can be ESA-naïve, or refractory or intolerant to, or ineligible for, prior ESA treatment, as defined by any one of the following:
• Refractory to prior ESA treatment - documentation of non-response or response that is no longer maintained to prior ESA-containing regimen, either as single agent or combination (eg, with G-CSF); ESA regimen must have been either:
• recombinant human erythropoietin (rHu EPO) ≥ 40,000 IU/wk for at least 8 doses or equivalent; OR
• darbepoetin alpha ≥ 200-500 μg Q1-3W for at least 4 doses or equivalent;
• Intolerant to prior ESA treatment - documentation of discontinuation of prior ESAcontaining regimen, either as single agent or combination (eg, with G-CSF), at any time after introduction due to intolerance or an adverse event
• ESA ineligible - Low chance of response to ESA based on endogenous serum erythropoietin level \> 200 U/L for subjects not previously treated with ESAs
• If previously treated with ESAs, agents must have been discontinued ≥ 4 weeks prior to date of C1D1.
• Requires RBC transfusions, as documented by the following criteria:
• average transfusion requirement of ≥ 2 units/8 weeks of packed Red Blood Cells (pRBC)s preceding C1D1.
• Hemoglobin levels at the time of or within 7 days prior to administration of a RBC transfusion must have been ≤ 10.0 g/dL for the transfusion to be counted towards meeting eligibility criteria. Red blood cell transfusions administered when Hgb levels were \> 10.0 g/dL and/or RBC transfusions administered for elective surgery will not qualify as a required transfusion for the purpose of meeting eligibility criteria.
• Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 (Appendix 1)
• Females of childbearing potential (FCBP), defined as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months), must:

You may not qualify if:

• Prior therapy with Lenalidomide.
• Previously treated with either luspatercept (ACE-536) or sotatercept (ACE-011)
• MDS associated with del 5q cytogenetic abnormality
• Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding
• iron deficiency to be determined by serum ferritin ≤ 15 μg/L and additional testing if clinically indicated (eg, calculated transferrin saturation \[iron/total iron binding capacity ≤ 20%\] or bone marrow aspirate stain for iron).
• Prior allogeneic stem cell transplant
• Known history of diagnosis of AML
• Use of any of the following within 4 weeks prior to C1D1:
• anticancer cytotoxic chemotherapeutic agent or treatment
• other RBC hematopoietic growth factors (eg, Interleukin-3)
• investigational drug or device, or approved therapy for investigational use. If the half-life of the previous investigational product is known, use within 5 times the half-life prior to C1D1 or within 5 weeks, whichever is longer is excluded.
• Uncontrolled hypertension, defined as repeated elevations of diastolic blood pressure (DBP) ≥ 100 mmHg despite adequate treatment.
• Prior history of malignancies, other than MDS, unless the subject has been free of the disease (including completion of any active or adjuvant treatment for prior malignancy) for ≥ 1 year. However, subjects with the following history/concurrent conditions involving in situ cancer (or similar) are allowed:
• Basal or squamous cell carcinoma of the skin
• Carcinoma in situ of the cervix

Sponsors & Collaborators

• Mikkael Sekeres, MD: lead
• Celgene: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (5)

University of Miami

Miami, Florida, 33136, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Lenalidomide; luspatercept

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Mikkael Sekeres, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 31, 2020
• First Posted: September 4, 2020
• Study Start: November 9, 2021
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: August 5, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)