Luspatercept for Myelodysplastic Syndrome

Overseen By Guillermo Garcia-Manero, M D

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Investigational agents, Chemotherapy

Disqualifiers: Active infection, Pregnancy, Active malignancy, others

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

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called luspatercept to determine if it can reduce the need for blood transfusions in individuals with lower-risk myelodysplastic syndrome (LR-MDS). The trial includes two groups: one for patients requiring regular blood transfusions and another for those who do not. The goal is to assess whether luspatercept can improve anemia symptoms in both groups. This trial may suit individuals diagnosed with LR-MDS, particularly if ongoing anemia affects their daily life. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in anemia treatment.

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 be on any other investigational drugs, chemotherapy, radiotherapy, or immunotherapy within 14 days before starting the study treatment.

Is there any evidence suggesting that luspatercept is likely to be safe for humans?

Research has shown that luspatercept is generally well-tolerated by patients with lower-risk myelodysplastic syndromes (MDS). In a study with Asian patients, luspatercept proved both effective and safe, offering an alternative to frequent blood transfusions. Another study found that only 2.1% of 242 patients treated with luspatercept experienced serious side effects. Long-term studies confirmed its safety in 108 patients with lower-risk MDS. These findings suggest that luspatercept is safe and could help reduce the need for blood transfusions in MDS patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for myelodysplastic syndrome?

Luspatercept is unique because it targets the underlying causes of anemia in myelodysplastic syndromes (MDS) by enhancing the maturation of red blood cells. Unlike standard treatments such as erythropoiesis-stimulating agents (ESAs), which aim to boost red blood cell production, Luspatercept works by a different mechanism, helping immature red blood cells develop into fully functional ones. This approach can be particularly beneficial for patients who are transfusion-dependent or have not responded well to ESAs. Researchers are excited about Luspatercept because it offers a new way to potentially reduce the need for blood transfusions and improve quality of life for MDS patients.

What evidence suggests that luspatercept might be an effective treatment for myelodysplastic syndrome?

Research has shown that luspatercept can reduce the need for blood transfusions in patients with lower-risk myelodysplastic syndromes (MDS). Studies indicate that patients taking luspatercept produce more red blood cells, reducing their need for transfusions. One study found that some patients even stopped needing regular blood transfusions altogether. In this trial, participants in Cohort 1, who are transfusion independent, and those in Cohort 2, who are transfusion dependent, will receive luspatercept. These findings suggest that luspatercept could be a promising option for managing anemia in people with lower-risk MDS, leading to fewer transfusions and a better quality of life. ^{1 6 7 8 9}

Who Is on the Research Team?

Guillermo Garcia-Manero

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults diagnosed with low-risk Myelodysplastic Syndromes (MDS) who need fewer blood transfusions. Cohort #1 includes those not needing transfusions for a hemoglobin level under 8.0 g/dL in the past 8 weeks, while Cohort #2 includes those dependent on at least two units of red blood cells within the same period. Participants must have adequate liver and kidney function, an ECOG performance status of ≤2, and agree to use contraception if they can have children.

Inclusion Criteria

I have been diagnosed with MDS and my risk level is low to intermediate-1.

I needed at least 2 blood transfusions due to low hemoglobin in the last 8 weeks.

I have anemia but haven't needed a blood transfusion for low hemoglobin in the last 8 weeks.

Exclusion Criteria

I have an infection that isn't getting better with antibiotics.

I have been treated with luspatercept or sotatercept before.

I am willing to use effective birth control during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive luspatercept. Participants will visit the clinic weekly for the first 3 weeks and then once every 3 weeks for tests and procedures.

12 weeks

3 visits (weekly), then 1 visit every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Luspatercept

Trial Overview The study is testing Luspatercept's effectiveness in reducing the need for blood transfusions in patients with lower risk MDS. It's an open-label pilot trial where all participants receive Luspatercept; there are no comparison groups or placebos involved.

How Is the Trial Designed?

Group I: Cohort 2 Experimental Treatment 1 Intervention

Participants with lower risk MDS that are transfusion dependent (TD). Participants will be asked to come to the study clinic weekly for the first 3 weeks and then 1 time every 3 weeks after that to have tests and procedures (such as physical exams and blood draws). Luspatercept will be administered once every 3 weeks.

Group II: Cohort 1 Experimental Treatment 1 Intervention

Participants with lower risk MDS patients who have symptomatic anemia that are transfusion independent (TI). Participants will be asked to come to the study clinic weekly for the first 3 weeks and then 1 time every 3 weeks after that to have tests and procedures (such as physical exams and blood draws). Luspatercept will be administered once every 3 weeks.

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

Approved in United States as Reblozyl for:

• Anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions
• Anemia in adults with transfusion-dependent anemia due to very low, low and intermediate-risk myelodysplastic syndromes (MDS) with ring sideroblasts

Approved in European Union as Reblozyl for:

• Anemia in adults with transfusion-dependent beta thalassemia
• Anemia in adults with transfusion-dependent anemia due to very low, low and intermediate-risk myelodysplastic syndromes (MDS) with ring sideroblasts

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

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]

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 (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 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]

Citations

1. news.bms.com news.bms.com/news/details/2025/Bristol-Myers-Squibb-Announces-Topline-Results-from-Phase-3-INDEPENDENCE-Trial-for-Reblozyl-luspatercept-aamt-in-Adult-Patients-with-Myelofibrosis-Associated-Anemia/default.aspx

Corporate news details INDEPENDENCE (NCT04717414) is a Phase 3, double-blind, randomized study to compare the efficacy and safety of luspatercept vs placebo in ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10878180/

Treatment patterns and outcomes with luspatercept in ... Treatment patterns and outcomes with luspatercept in patients with lower‐risk myelodysplastic syndromes: A retrospective US cohort analysis

3. 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.

4. reblozyl.com reblozyl.com/mds/how-reblozyl-works/second-line-results

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

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6570

Real-world (RW) outcomes of patients (pts) with lower-risk ... This is the first study assessing RW characteristics and outcomes in pts with LR-MDS receiving 1L LUSPA or ESA after 1L LUSPA approval.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11843707/

Safety and efficacy of luspatercept in treating anemia ... These results support luspatercept as a well-tolerated, efficacious alternative to transfusions for Asian patients with lower-risk MDS, who tend ...

7. reblozylpro.com reblozylpro.com/mds-second-line/safety

REBLOZYL® (luspatercept-aamt) Second Line Safety Among the 242 patients treated with REBLOZYL, 5 (2.1%) had a fatal adverse reaction1; Selected laboratory abnormalities that changed from Grade 0 to 1 at ...

8. 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 ...

9. 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- ...