Luspatercept vs Epoetin Alfa for MDS-related Anemia

(COMMANDS Trial)

Recruiting at 454 trial locations

Overseen By BMS Study Connect Contact www.BMSStudyConnect.com

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Celgene

Disqualifiers: Iron deficiency, B12 deficiency, Folate deficiency, Autoimmune anemia, AML, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

363 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine the effectiveness of luspatercept (ACE-536) compared to epoetin alfa on red blood cell (RBC) transfusion independence (for at least 12 weeks) with a concurrent hemoglobin increase of at least 1.5 g/dL in participants with anemia due to revised international prognostic scoring system (IPSS-R) very low, low, or intermediate risk myelodysplastic syndromes (MDS) who require RBC transfusions and have never been exposed to erythropoiesis stimulating agent (ESA).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Luspatercept for treating MDS-related anemia?

Luspatercept has shown promising results in reducing the need for red blood cell transfusions in patients with myelodysplastic syndromes (MDS) who have not responded to other treatments. In clinical trials, it has been effective in promoting late-stage red blood cell development, helping some patients achieve hematologic improvement and even transfusion independence. ^{1 2 3 4 5}

Is Luspatercept safe for humans?

Luspatercept has been generally well-tolerated in clinical trials, but some people experienced side effects like blood clots, high blood pressure, and bone pain. ^{1 3 4 5 6}

How is the drug Luspatercept different from other treatments for MDS-related anemia?

Luspatercept is unique because it is an erythroid maturation agent that helps mature red blood cells at a later stage, unlike traditional treatments that stimulate early red blood cell production. It is administered subcutaneously (under the skin) every three weeks and has shown durable efficacy in reducing the need for blood transfusions in patients with myelodysplastic syndromes. ^{1 3 4 6 7}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for people with very low to intermediate risk Myelodysplastic Syndromes (MDS) who need regular blood transfusions and have never used an ESA. They should have less than 5% bone marrow blasts, be relatively active (ECOG score of 0-2), and not suffer from other causes of anemia or conditions like uncontrolled high blood pressure or Acute myeloid leukemia.

Inclusion Criteria

I have a type of blood disorder called MDS, with a low to intermediate risk and less than 5% cancer cells in my bone marrow.

I've needed 2-6 blood transfusions every 8 weeks for the last 2 months.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I have been diagnosed with Acute myeloid leukemia (AML).

My high blood pressure is not controlled even with treatment.

I have anemia caused by a deficiency, autoimmune condition, or medication.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either luspatercept or epoetin alfa to assess red blood cell transfusion independence and hemoglobin increase

24 weeks

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

42 days post last dose

Long-term Follow-up

Participants are monitored for progression to acute myeloid leukemia and overall survival

Up to 5 years

Treatment Details

Interventions

• Epoetin alfa
• Luspatercept

Trial Overview The study compares Luspatercept (ACE-536) with Epoetin alfa in treating anemia caused by MDS. It aims to see if patients can avoid red blood cell transfusions for at least 12 weeks while also increasing their hemoglobin levels by at least 1.5 g/dL.

Participant Groups

Group I: Luspatercept Experimental Treatment 1 Intervention

Group II: Epoetin alfa Active Control 1 Intervention

Who Is Running the Clinical Trial?

Celgene

Lead Sponsor

Trials

649

Recruited

130,000+

Top Products

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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

Acceleron Pharma Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)

Industry Sponsor

Trials

33

Recruited

4,300+

Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA

Industry Sponsor

Trials

33

Recruited

4,300+

Findings from Research

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 (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 (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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Luspatercept in Myelodysplastic Syndromes: Who and When? [2021]

2. England pubmed.ncbi.nlm.nih.gov

Luspatercept in combination with recombinant erythropoietin in patients with myelodysplastic syndrome with ring sideroblasts: Stimulating early and late-stage erythropoiesis. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): interim analysis of a phase 3, open-label, randomised controlled trial. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

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

5. England 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. [2019]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Luspatercept: First Approval. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics and Exposure-Response of Luspatercept, an Erythroid Maturation Agent, in Anemic Patients With Myelodysplastic Syndromes. [2021]