Luspatercept + Lenalidomide for Myelodysplastic Syndrome

Not currently recruiting at 7 trial locations

Overseen By Mikkael Sekeres, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Mikkael Sekeres MD

Must not be taking: Lenalidomide, Luspatercept, Sotatercept, others

Disqualifiers: AML, Uncontrolled hypertension, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining Lenalidomide (Revlimid) and Luspatercept (Reblozyl) can more effectively treat anemia in individuals with lower-risk Myelodysplastic Syndrome (MDS), a type of blood disorder. The study explores different doses of these drugs to identify the most effective one. Suitable participants have MDS, require regular blood transfusions, and have not succeeded with or cannot take certain anemia treatments. As a Phase 1, Phase 2 trial, this research aims to understand the treatment's mechanism and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken certain treatments like anticancer drugs or investigational drugs within 4 weeks before starting the trial. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using Luspatercept and Lenalidomide together is generally safe for patients with lower-risk Myelodysplastic Syndrome (MDS). Most patients tolerate this drug combination well. Some experienced side effects, but these were manageable. The most common side effects included tiredness and nausea, while serious problems were rare.

These results come from studies on patients with non-del(5q) MDS, a specific type of MDS. The treatment demonstrated promising safety and early effectiveness in these patients, suggesting the combination could improve anemia (low red blood cell levels) in MDS without causing severe side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Luspatercept and Lenalidomide for treating Myelodysplastic Syndrome because of their distinct mechanisms of action. Unlike traditional treatments like azacitidine or decitabine, which primarily target cancer cells by interfering with DNA synthesis, Luspatercept works by enhancing red blood cell production, potentially reducing the need for transfusions. Lenalidomide, on the other hand, modulates the immune system and inhibits the growth of abnormal blood cells. Together, these drugs offer a novel approach that not only addresses the disease's symptoms but also targets its underlying causes, giving hope for improved patient outcomes.

What evidence suggests that the combination of Lenalidomide and Luspatercept could be effective for treating anemia in lower-risk Myelodysplastic Syndrome?

Research has shown that using Lenalidomide and Luspatercept together can improve anemia in patients with lower-risk Myelodysplastic Syndrome (MDS). One study found that half of the patients experienced improved blood cell counts. In this trial, participants will receive the combination of Lenalidomide and Luspatercept. Luspatercept alone has also lessened anemia in some types of MDS, potentially reducing the need for blood transfusions and greatly enhancing quality of life. Overall, early research suggests that this drug combination might effectively treat anemia in MDS patients. ^{1 2 3 4 6}

Who Is on the Research Team?

Mikkael A Sekeres, MD, MS

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

Adults with lower-risk Myelodysplastic Syndrome (MDS) who haven't responded to or can't take Erythropoiesis-stimulating agents, and need regular blood transfusions. Participants must not be pregnant, agree to contraception if of childbearing potential, have no severe medical conditions or recent major surgeries, and cannot have had certain prior treatments like stem cell transplants.

Inclusion Criteria

Subject must have a negative Coronavirus Disease of 2019 (COVID-19) test completed ≤7 days prior to administration of protocol therapy.

I am able to care for myself and perform daily activities.

- no consecutive 56-day period that was RBC transfusion-free during the 16 weeks immediately preceding C1D1.

Exclusion Criteria

My MDS is linked to a specific genetic change (del 5q).

I am not taking any red blood cell growth factors like Interleukin-3.

I have anemia caused by a deficiency or bleeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase Ib Treatment

Luspatercept and Lenalidomide are administered in a dose escalation design to determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)

15 weeks

Phase II Treatment

Luspatercept and Lenalidomide are administered at the RP2D for 21 days on a 21-day cycle, continuing as long as clinical benefit is derived, up to 5 years

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lenalidomide
• Luspatercept

Trial Overview

The trial is testing whether combining two drugs, Luspatercept and Lenalidomide (referred to as L2), is effective in treating anemia in patients with MDS that doesn't involve chromosome 5q deletion. The study aims to see if this drug combo improves upon current anemia treatments.

How Is the Trial Designed?

Group I: Luspatercept + Lenalidomide Group Experimental Treatment 2 Interventions

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.

Lenalidomide is already approved in European Union, United States for the following indications:

Approved in European Union as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Approved in United States as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Who Is Running the Clinical Trial?

Mikkael Sekeres MD

Lead Sponsor

Trials

2

Recruited

90+

Mikkael Sekeres, MD

Lead Sponsor

Trials

1

Recruited

50+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Celgene

Industry Sponsor

Trials

649

Recruited

130,000+

Top Products

>- **Revlimid (lenalidomide)**: Multiple myeloma, myelodysplastic syndromes, and mantle cell lymphoma treatment. - **Pomalyst (pomalidomide)**: Relapsed/refractory multiple myeloma treatment. - **Otezla (apremilast)**: Psoriatic arthritis treatment. - **Thalomid (thalidomide)**: Erythema nodosum leprosum and multiple myeloma treatment.

Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Published Research Related to This Trial

Luspatercept is effective in treating transfusion-dependent anemia in patients with myelodysplastic syndromes (MDS) and beta thalassemia, showing a significantly higher percentage of patients achieving transfusion independence compared to placebo (37.91% vs 13.16% for MDS and 21.4% vs 4.5% for beta thalassemia, both P < 0.0001).

While luspatercept has a similar overall incidence of adverse events compared to placebo, it is associated with higher rates of grade ≥3 adverse events and serious adverse events, with common side effects including headache, back pain, and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency Review of Luspatercept for the Treatment of Adult Patients With Transfusion-dependent Anemia Caused by Low-risk Myelodysplastic Syndromes With Ring Sideroblasts or Beta-thalassemia. Delgado, J., Voltz, C., Stain, M., et al.[2021]

Luspatercept is a novel treatment that targets anemia in patients with myelodysplastic syndrome (MDS), particularly effective for those with ring sideroblast subtypes.

This agent works by addressing the impaired red blood cell production seen in MDS, offering a new option for patients who have not responded to traditional erythroid-stimulating agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Luspatercept in Myelodysplastic Syndromes: Who and When? Komrokji, RS.[2021]

Luspatercept is a newly approved treatment for anemia in patients with lower-risk myelodysplastic syndromes (LR-MDS), showing significant efficacy in a phase III trial where 38% of patients achieved transfusion independence compared to only 13% in the placebo group.

The treatment has a favorable safety profile, with common side effects like fatigue and dizziness occurring more frequently in the initial treatment cycles but decreasing over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of Luspatercept in the Management of Lower-Risk Myelodysplastic Syndromes. Tinsley-Vance, SM., Davis, M., Ajayi, O.[2023]

Luspatercept (Reblozyl®) is an effective treatment for adults with transfusion-dependent anemia due to myelodysplastic syndromes (MDS) or β-thalassemia, significantly reducing the need for red blood cell transfusions in pivotal phase III trials.

The treatment has a generally manageable safety profile, although patients may experience specific adverse events such as thromboembolic events, hypertension, and bone pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Luspatercept: A Review in Transfusion-Dependent Anaemia due to Myelodysplastic Syndromes or β-Thalassaemia. Kang, C., Syed, YY.[2021]

In a phase 2 study involving 58 patients with lower-risk myelodysplastic syndromes, luspatercept demonstrated significant efficacy, with 63% of patients receiving higher doses (0.75-1.75 mg/kg) achieving hematological improvement compared to only 22% in the lower dose group (0.125-0.5 mg/kg).

Luspatercept was well tolerated, with only three treatment-related grade 3 adverse events reported, indicating a favorable safety profile for this novel therapy in treating anemia associated with myelodysplastic syndromes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Luspatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes (PACE-MDS): a multicentre, open-label phase 2 dose-finding study with long-term extension study. Platzbecker, U., Germing, U., Götze, KS., et al.[2019]

Luspatercept-aamt, approved by the FDA in April 2020, effectively promotes erythroid maturation and demonstrated significant efficacy in the MEDALIST trial, achieving transfusion independence in patients with refractory myelodysplastic syndromes.

Decitabine/cedazuridine, approved in July 2020, acts as a nucleoside metabolic inhibitor and showed comparable safety and efficacy to IV decitabine in the ASCERTAIN study, making it a viable treatment option for patients with intermediate or high-risk myelodysplastic syndromes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel agents for myelodysplastic syndromes. Xu, K., Hansen, E.[2022]

Luspatercept (REBLOZYL®) is an erythroid maturation agent approved for treating anemia linked to beta-thalassemia, myelodysplastic syndromes, and myelofibrosis.

The approval was primarily based on the positive results from the phase III BELIEVE trial, highlighting its efficacy in improving hemoglobin levels in patients with beta-thalassemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Luspatercept: First Approval. Markham, A.[2020]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11814532/

Response to luspatercept can be predicted and improves ...

Response to luspatercept can be predicted and improves overall survival in the real‐life treatment of LR‐MDS

2.

ashpublications.org

ashpublications.org/blood/article/144/Supplement%201/1821/529874/A-Multicenter-Phase-Ib-II-Study-That-Combines

A Multicenter, Phase Ib/II Study That Combines Luspatercept ...

Real-World Outcomes of Patients with Lower-Risk Myelodysplastic Syndromes (LR-MDS) Treated with Luspatercept: An Evaluation of US Clinical ...

3.

onclive.com

onclive.com/view/luspatercept-lenalidomide-combo-demonstrates-safety-and-early-efficacy-in-lower-risk-non-del-5q-mds

Luspatercept/Lenalidomide Combo Demonstrates Safety ...

Efficacy data showed that among evaluable patients (n = 10), 50% experienced hematologic improvement. The rates of hematologic improvement– ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04539236

Luspatercept and Lenalidomide (L2) in Lower-risk, Non-del ...

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 ...

5.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1908892

Luspatercept in Patients with Lower-Risk Myelodysplastic ...

Luspatercept reduced the severity of anemia in patients with lower-risk myelodysplastic syndromes with ring sideroblasts who had been receiving regular red- ...

6.

cancer.gov

cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-12641

Luspatercept and Lenalidomide for the Treatment of ...

This phase Ib/II trial tests the safety, side effects, and best dose of luspatercept in combination with lenalidomide and whether they work in treating anemia