Luspatercept vs Epoetin Alfa for MDS-related Anemia

(COMMANDS Trial)

Not currently recruiting at 518 trial locations

Overseen By rami komrokji, Site 108

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, luspatercept (Reblozyl) and epoetin alfa, to determine which better reduces red blood cell transfusion dependence in people with anemia related to myelodysplastic syndromes (a group of blood disorders). The trial aims to discover if these treatments can maintain higher hemoglobin levels, increasing oxygen in the blood. Suitable candidates for this trial include those diagnosed with certain lower-risk types of myelodysplastic syndromes, who require regular blood transfusions, and have not previously received similar anemia medications. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that luspatercept is already FDA-approved for treating anemia in patients with blood disorders like β-thalassemia, indicating its safety for people. Studies have also found that luspatercept effectively treats anemia related to myelodysplastic syndromes (MDS). In earlier research, patients tolerated luspatercept well, with most side effects being mild to moderate.

Epoetin alfa, another well-known treatment, helps the body produce more red blood cells. Its long history of use in treating anemia across various conditions supports its safety.

Both luspatercept and epoetin alfa have proven safety records, making them promising options for those considering participation in a clinical trial for MDS-related anemia. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for MDS-related anemia?

Researchers are excited about Luspatercept for MDS-related anemia because it offers a novel approach compared to standard treatments like Epoetin alfa. Most anemia treatments work by stimulating the production of red blood cells, but Luspatercept works differently by enhancing the maturation of red blood cells. This unique mechanism could potentially lead to more effective management of anemia with fewer side effects. Additionally, Luspatercept might reduce the need for frequent blood transfusions, which can be a significant advantage for patients.

What evidence suggests that this trial's treatments could be effective for MDS-related anemia?

Research has shown that luspatercept, one of the treatments studied in this trial, effectively treats anemia related to myelodysplastic syndromes (MDS). It outperforms traditional treatments like erythropoiesis-stimulating agents (ESAs), such as epoetin alfa, the comparator treatment in this trial, which helps increase red blood cell production. In clinical trials, luspatercept reduced the need for blood transfusions in patients with MDS. Additionally, the U.S. FDA has approved luspatercept as a first-choice treatment for this condition, highlighting its proven effectiveness. Patients using luspatercept are likely to experience significant improvements in managing anemia compared to those using traditional therapies like epoetin alfa. ^{2 6 7 8 9}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

>- **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

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+

Published Research Related to This Trial

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]

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]

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 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]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03900715

An Efficacy and Safety Study of Luspatercept (ACE-536) for ...

The goal of this study is to assess the efficacy, safety and PK of luspatercept in anemic patients who are categorized as International Prognostic Scoring ...

2.

reblozyl.com

reblozyl.com/mds/how-reblozyl-works/first-line-results

First Line Results - REBLOZYL® (luspatercept-aamt)

Learn about the first-line treatment results and side effects of REBLOZYL® (luspatercept-aamt) for patients with anemia in myelodysplastic syndromes (MDS).

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S0145212624001905

Real-world impact of luspatercept on red blood cell ...

Myelodysplastic syndromes (MDS) are associated with anemia and the need for blood transfusions. In clinical trials, luspatercept reduced transfusion ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9671752/

Long-Term Efficacy and Safety of Luspatercept for Anemia ...

This study highlights luspatercept's effects across LR-MDS subtypes, including untreated MDS-RS, serving as a platform for future trials.

5.

news.bms.com

news.bms.com/news/details/2023/U.S.-FDA-Approves-Bristol-Myers-Squibbs-Reblozyl-luspatercept-aamt-as-First-Line-Treatment-of-Anemia-in-Adults-with-Lower-Risk-Myelodysplastic-Syndromes-MDS-Who-May-Require-Transfusions/default.aspx

U.S. FDA Approves Bristol Myers Squibb's Reblozyl® ...

Reblozyl is the first and only therapy to demonstrate superiority compared to an erythropoiesis stimulating agent (ESA) in MDS-related anemia.

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/35998303/

Long-Term Efficacy and Safety of Luspatercept for Anemia ...

We report long-term luspatercept safety and efficacy in 108 patients with LR-MDS in the PACE-MDS study, including 44 non-RS and 34 non- ...

7.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK560635/

Luspatercept - StatPearls - NCBI Bookshelf - NIH

Luspatercept is an FDA-approved recombinant fusion protein used to manage anemia in patients with β-thalassemia who require regular blood transfusions.

8.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03682536

NCT03682536 | A Study to Compare the Efficacy and ...

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.

9.

ashpublications.org

ashpublications.org/bloodadvances/article/8/17/4511/516341/Safety-and-efficacy-of-luspatercept-for-the

Safety and efficacy of luspatercept for the treatment of anemia ...

Median time to anemia response was 63.0 days (range, 41-68) and 63.5 days (range, 42-85) in cohort 1 and cohort 3A, respectively.