Luspatercept for Clonal Cytopenia

Overseen By Ameenah Sukkur, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Weill Medical College of Cornell University

Must not be taking: ESA, Growth factors

Disqualifiers: Concurrent malignancy, MDS, AML, 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

Compensation: Varies

Number of Visits: 8

Duration: 24 weeks

50 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this clinical trial is to test how well the drug luspatercept works in improving low blood cell counts in people with clonal cytopenias of uncertain significance (CCUS). The main questions the study seeks to answer include: * How many patients experience improvements in their low blood counts (red cells, platelets, or white cells) within 24 weeks, based on specific criteria for blood conditions like myelodysplastic syndromes (MDS)? * How long these improvements last before the condition worsens or changes. * The percentage of participants showing improvements at 12, 24, and 48 weeks. * How long it takes for the condition to progress to more severe diseases like myeloid disorders. * How long red blood cell responses last and how quickly these responses are seen. * The average change in hemoglobin levels over 24 weeks. * How many patients need blood transfusions during the study and how soon transfusions are required. * Changes in participants' well-being and energy levels based on a standardized questionnaire. * Monitoring for any side effects, including progression to MDS or leukemia, heart-related issues, or sudden increases in hemoglobin. Participants will: * Receive luspatercept as an injection every three weeks. * Visit the clinic every three weeks for treatment and monitoring.

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

The trial does not specify if you need to stop taking your current medications. However, you cannot have used ESA (erythropoiesis-stimulating agents) or growth factors within four weeks before starting the study.

What data supports the effectiveness of the drug Luspatercept for treating clonal cytopenia?

Luspatercept has been shown to be effective in reducing the need for blood transfusions in patients with certain types of anemia, such as those caused by myelodysplastic syndromes and beta-thalassemia. In clinical trials, a significant percentage of patients achieved transfusion independence or a reduction in transfusion burden when treated with Luspatercept compared to a placebo. ^{1 2 3 4 5}

How does the drug Luspatercept differ from other treatments for clonal cytopenia?

Luspatercept is unique because it is designed to specifically target and improve red blood cell production, which can be beneficial for conditions like clonal cytopenia where blood cell production is impaired. Unlike other treatments that may focus on suppressing the immune system or managing symptoms, Luspatercept works by enhancing the maturation of red blood cells, offering a novel approach to treatment. ^{6 7 8 9 10}

Research Team

Pinkal Desai, MD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

This trial is for people with clonal cytopenias of uncertain significance (CCUS), which means they have low counts of red cells, platelets, or white cells without a clear reason. Participants should not have progressed to more severe blood disorders and must be able to attend clinic visits every three weeks.

Inclusion Criteria

I can have children, have had two negative pregnancy tests, and will use effective birth control or abstain from sex.

Documentation of a CCUS diagnosis

My blood or bone marrow test shows specific gene mutations related to myeloid cancer.

Exclusion Criteria

I am currently receiving treatment for another cancer.

I haven't used any blood cell growth boosters in the last 4 weeks.

I am at risk for blood clots.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive luspatercept as an injection every three weeks to improve low blood cell counts

24 weeks

8 visits (in-person, every 3 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including progression to myeloid disorders and changes in quality of life

24 weeks

Long-term Follow-up

Participants are monitored for long-term outcomes such as transfusion dependence and quality of life changes

48 weeks

Treatment Details

Interventions

• Luspatercept

Trial Overview The study tests luspatercept injections given every three weeks to see if it improves blood counts in CCUS patients. It measures the number of patients who improve within 24 weeks, duration of improvement, time until disease progression, changes in hemoglobin levels, transfusion needs, and overall well-being.

Participant Groups

Group I: Luspatercept Experimental Treatment 1 Intervention

Luspatercept administered at 1 mg/kg IV once every 3 weeks

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

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 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]

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]

References

1. 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]

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

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

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

Population Pharmacokinetics and Exposure-Response of Luspatercept, an Erythroid Maturation Agent, in Anemic Patients With Myelodysplastic Syndromes. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): interim analysis of a phase 3, open-label, randomised controlled trial. [2023]

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

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

6. England pubmed.ncbi.nlm.nih.gov

The effect of treatment with Campath-1H in patients with autoimmune cytopenias. [2019]

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

Autoimmune thrombocytopenia: a complication of fludarabine therapy in lymphoproliferative disorders. [2019]

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

Eltrombopag Improves Refractory Thrombocytopenia in a Patient with Systemic Lupus Erythematosus. [2020]

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

Treatment of autoimmune cytopenia complicating progressive chronic lymphocytic leukemia/small lymphocytic lymphoma with rituximab, cyclophosphamide, vincristine, and prednisone. [2021]

10. Greece pubmed.ncbi.nlm.nih.gov

Lupus thrombocytopenia: pathogenesis and therapeutic implications. [2020]