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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the drug luspatercept (also known as Reblozyl, Luspatercept-aamt, ACE-536, or BMS-986346) can reduce the need for regular blood transfusions in individuals with myelodysplastic syndrome (MDS) or MDS/myeloproliferative neoplasms (MDS/MPN). The study focuses on the safety and effects of this treatment on anemia, a condition where the body lacks enough healthy red blood cells. Participants will be divided into two groups: one with specific gene mutations other than SF3B1, and another with the SF3B1 mutation. Suitable candidates for this trial include those with MDS who require frequent blood transfusions and have not responded to other treatments like ESAs (medications used to treat anemia). As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group of people.

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.

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

Research shows that luspatercept is generally well-tolerated. The FDA has approved it for treating anemia in people with β-thalassemia, indicating it has passed safety checks for that use. In studies involving patients with myelofibrosis, a bone marrow disorder, luspatercept improved anemia with manageable side effects.

Another study compared luspatercept to a placebo (a substance with no active ingredients) in patients with anemia, providing more evidence of its safety. The most common side effects were tiredness, headaches, and joint pain, which were usually mild to moderate.

Overall, luspatercept has been studied in various contexts, and results suggest it is generally safe with some minor side effects. ^{1 2 3 4 5}

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

Researchers are excited about luspatercept for treating myelodysplastic syndrome-related anemia because it offers a unique approach compared to current options like erythropoiesis-stimulating agents, hypomethylating agents, and lenalidomide. Unlike these standard treatments, which mainly boost red blood cell production or modify the immune response, luspatercept works by targeting the TGF-beta superfamily signaling pathways. This mechanism is designed to enhance late-stage red blood cell maturation, potentially leading to more effective anemia management. Additionally, luspatercept has shown promise in helping patients with specific gene mutations, such as SF3B1, who have not responded well to other therapies. This targeted action provides hope for improved outcomes in a group of patients with limited options.

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

Research has shown that luspatercept can help manage anemia in people with myelodysplastic syndromes (MDS). Studies have found that patients using luspatercept achieve better hemoglobin levels, reducing their need for blood transfusions. In this trial, participants with lower-risk MDS or non-proliferative MDS/MPN will receive luspatercept. One group will have gene mutations other than SF3B1, while another group will have the SF3B1 mutation. For those with lower-risk MDS, luspatercept has effectively reduced anemia symptoms, improving quality of life. This treatment is already approved for anemia in conditions like β-thalassemia, which also requires frequent blood transfusions. Overall, luspatercept shows promise for treating anemia related to MDS, offering hope for better management of the condition. ^{1 2 3 6 7}

Who Is on the Research Team?

Rami Komrokji, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

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

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

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

My cancer has a specific gene mutation related to splicing.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 (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]

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]

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]

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]

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]

Citations

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Corporate news details “It is promising to see that Reblozyl led to clinically relevant improvement of anemia for patients with myelofibrosis, where patients often ...

2. 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.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02631070

NCT02631070 | A Study of Luspatercept (ACE-536) to ... This is a Phase 3, double-blind, randomized, placebo-controlled, multicenter study to determine the efficacy and safety of luspatercept (ACE-536) versus placebo ...

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Anemia in MDS & Beta Thalassemia (BT) Treatment ... REBLOZYL® (luspatercept-aamt) is a prescription medicine used to treat patients with anemia in myelodysplastic syndromes (MDS) & anemia in beta thalassemia ...

5. reblozylpro.com reblozylpro.com/mds-first-line/hgb-data

REBLOZYL® (luspatercept-aamt) First Line HGB Data - LR-MDS On the Anemia Subscale, results include: 1.54 (1.23, 1.84) for change from baseline in Hgb (continuous); 1.76 (1.13, 2.38) for change from baseline in Hgb (≥1.5 ...

6. reblozylpro.com reblozylpro.com/

REBLOZYL® (luspatercept-aamt) | For HCPs REBLOZYL: the only FDA approved first-line treatment for patients with MDS associated anemia · Explore results from the only head-to-head study vs an ESA in ...

7. 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 ... Luspatercept improved anemia in patients with MF with/without transfusion dependence, particularly those receiving ruxolitinib.