Luspatercept for Myelodysplastic Syndrome-related Anemia

Overseen By Rami Komrokji, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Luspatercept, Sotatercept

Disqualifiers: Stem cell transplant, Hypertension, Renal impairment, 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: Unknown

Duration: 18 months

70 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to see if participants with anemia due to their type of MDS or MDS/MPN will experience a more decreased need for regular blood transfusions if they take luspatercept plus best supportive care, and what effect, good and/or bad, luspatercept has on them and their anemia due to MDS or MDS/MPN. The safety and tolerability of luspatercept will also be evaluated in this study.

Do I need to stop my current medications for the trial?

The trial requires that you stop taking ESAs (erythropoiesis-stimulating agents), G-CSF (granulocyte colony-stimulating factor), and GM-CSF (granulocyte-macrophage colony-stimulating factor) at least 4 weeks before starting the study treatment.

What data supports the effectiveness of the drug Luspatercept for treating anemia related to myelodysplastic syndromes?

Luspatercept has been shown to significantly reduce the need for red blood cell transfusions in patients with myelodysplastic syndromes (MDS) and beta-thalassemia, as demonstrated in phase III trials. In these studies, a higher percentage of patients achieved transfusion independence or a reduction in transfusion burden compared to those receiving a placebo. ^{1 2 3 4 5}

What makes the drug Luspatercept unique for treating Myelodysplastic Syndrome-related Anemia?

Luspatercept is unique because it works by enhancing the maturation of red blood cells, which is different from traditional treatments that often focus on stimulating the production of these cells. This novel mechanism can help reduce the need for blood transfusions in patients with anemia related to Myelodysplastic Syndrome. ^{6 7 8 9 10}

Research Team

Rami Komrokji, MD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

This trial is for adults with certain types of bone marrow disorders (MDS or MDS/MPN) that cause anemia and require regular blood transfusions. Participants must have specific genetic mutations, not be pregnant or breastfeeding, and cannot have severe kidney issues or other active cancers. They should not have had prior stem cell transplants and must agree to contraception if applicable.

Inclusion Criteria

I am 18 years old or older.

My condition is classified as very low, low, or intermediate risk.

I have an SF3B1 mutation and was treated with hypomethylating agents or lenalidomide.

Exclusion Criteria

ALT or AST ≥ 3 × ULN

Platelet count ˂50,000/μL (50 x 109/L)

My MDS is linked to a specific genetic change and I haven't had lenalidomide.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive luspatercept plus best supportive care to evaluate its effect on anemia and the need for blood transfusions

18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

Treatment Details

Interventions

• Luspatercept

Trial Overview The study tests whether Luspatercept plus supportive care reduces the need for blood transfusions in patients with anemia due to MDS or MDS/MPN. It also assesses the safety and side effects of Luspatercept in these patients.

Participant Groups

Group I: Participants with gene mutations other than SF3B1 Experimental Treatment 1 Intervention

Participants with lower risk MDS or non-proliferative MDS/MPN with somatic splicing gene mutations other than SF3B1

Group II: Participants with SF3B1 mutation Experimental Treatment 1 Intervention

Participants with lower risk MDS or non-proliferative MDS/MPN with SF3B1 mutation who had received hypomethylating agents and or lenalidomide.

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?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

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

Findings from Research

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]

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 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 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]

A highly sensitive and rapid method for measuring bepotastine in human plasma was developed using ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS), achieving a quantitation limit of 0.2 ng/mL.

The method demonstrated high accuracy and precision, making it suitable for pharmacokinetic studies of bepotastine, which is important for understanding its absorption and effects in the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

UPLC-MS/MS method for determination of bepotastine in human plasma. Choi, YK., Chung, YH., Nam, YS., et al.[2016]

In a study involving 177 patients with active mild to moderate ulcerative colitis, the oral formulation of beclometasone dipropionate (BDP) was found to be as effective as 5-ASA in reducing disease activity, with 63% of BDP patients achieving clinical remission compared to 62.5% for 5-ASA.

Both treatments were well tolerated, and while BDP did lower mean plasma cortisol levels, there were no signs of significant adrenal function depletion, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral beclometasone dipropionate in the treatment of extensive and left-sided active ulcerative colitis: a multicentre randomised study. Campieri, M., Adamo, S., Valpiani, D., et al.[2019]

In a phase 2 clinical trial involving 362 patients, mesalazine micropellets were found to be as effective as traditional tablet formulations in achieving clinical remission for mild-to-moderate ulcerative colitis within 8 weeks.

The micropellet formulation allows for less frequent dosing and easier swallowing, which may enhance patient compliance and overall treatment experience without increasing the risk of adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesalazine (5-aminosalicylic acid) micropellets show similar efficacy and tolerability to mesalazine tablets in patients with ulcerative colitis--results from a randomized-controlled trial. Raedler, A., Behrens, C., Bias, P.[2022]

A review of four randomized controlled trials involving 428 patients with ulcerative colitis found that beclomethasone dipropionate (BDP) is as effective as 5-aminosalicylic acid (5-ASA) in controlling symptoms of left-sided mild to moderate ulcerative colitis.

Specifically, 69.9% of patients treated with 5-ASA showed improvement or remission compared to 65.3% of those treated with BDP, indicating that both treatments are similarly effective for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis: the efficacy of rectal beclomethasone dipropionate vs. 5-aminosalicylic acid in mild to moderate distal ulcerative colitis. Manguso, F., Balzano, A.[2013]

Oral beclomethasone dipropionate (BDP) significantly reduced Crohn's Disease Activity Index (CDAI) scores in 34 patients over 24 weeks, indicating its efficacy in treating mild-to-moderate Crohn's disease.

BDP was well tolerated with minimal adverse effects, suggesting it is a safer alternative to conventional glucocorticosteroids for managing Crohn's disease, especially in female non-smokers who showed the best treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral beclomethasone dipropionate for ileal or ileal-right colon Crohn's disease of mild-to-moderate activity or in remission: Retrospective study. Astegiano, M., Pagano, N., Sapone, N., et al.[2013]

References

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

Luspatercept: First Approval. [2020]

2. 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]

3. 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]

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

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

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

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

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

UPLC-MS/MS method for determination of bepotastine in human plasma. [2016]

7. England pubmed.ncbi.nlm.nih.gov

Oral beclometasone dipropionate in the treatment of extensive and left-sided active ulcerative colitis: a multicentre randomised study. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Mesalazine (5-aminosalicylic acid) micropellets show similar efficacy and tolerability to mesalazine tablets in patients with ulcerative colitis--results from a randomized-controlled trial. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Meta-analysis: the efficacy of rectal beclomethasone dipropionate vs. 5-aminosalicylic acid in mild to moderate distal ulcerative colitis. [2013]

10. France pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral beclomethasone dipropionate for ileal or ileal-right colon Crohn's disease of mild-to-moderate activity or in remission: Retrospective study. [2013]