Luspatercept for Myelodysplastic Syndrome

Recruiting in Houston (>99 mi)

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

Trial Summary

What is the purpose of this trial?

To learn if luspatercept is more effective in helping to reduce the number of blood transfusions needed by patients with LR-MDS.

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.

What data supports the effectiveness of the drug Luspatercept for treating myelodysplastic syndrome?

Luspatercept has been shown to significantly reduce the need for red blood cell transfusions in patients with myelodysplastic syndromes, with 38% of patients achieving transfusion independence compared to 13% with a placebo. This suggests that Luspatercept can effectively help manage anemia in these patients. ^{1 2 3 4 5}

Research Team

Guillermo Garcia-Manero

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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 am 18 years old or older.

I needed at least 2 blood transfusions due to 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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 (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 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 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]

References

1. 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]

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

Luspatercept: First Approval. [2020]

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

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

4. United States 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. [2021]

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

Role of Luspatercept in the Management of Lower-Risk Myelodysplastic Syndromes. [2023]