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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well the drug luspatercept helps people with clonal cytopenias of uncertain significance (CCUS), a condition characterized by low blood cell counts without a clear cause. Researchers aim to determine if luspatercept can improve blood counts and the duration of these improvements. The trial will also assess whether the drug can alleviate symptoms like fatigue and reduce the need for blood transfusions. Individuals diagnosed with CCUS who experience significant issues, such as requiring blood transfusions or frequent infections, might be suitable candidates for this study. Participants will receive luspatercept injections every three weeks and visit the clinic regularly for monitoring. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that luspatercept is generally well-tolerated. Most side effects were mild and manageable. Serious side effects occurred in about 31% of patients taking luspatercept, similar to those taking a placebo (a substance with no active drug). Importantly, no new safety concerns have appeared over three years of follow-up. Luspatercept has not shown any unexpected risks, making it a promising treatment option. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Luspatercept for clonal cytopenia because it offers a new approach by targeting the TGF-beta superfamily signaling pathway, which is different from current treatments like blood transfusions or erythropoiesis-stimulating agents. This novel mechanism aims to enhance red blood cell production more directly and effectively. Additionally, Luspatercept's administration as an intravenous treatment every three weeks could provide a more convenient option compared to more frequent treatments, potentially improving patients' quality of life.

What evidence suggests that luspatercept might be an effective treatment for clonal cytopenia?

Studies have shown that luspatercept, the treatment being tested in this trial, can increase blood cell counts in patients with clonal cytopenias of uncertain significance (CCUS). In a previous study, 83.3% of patients experienced improvements in their blood counts within the first 24 weeks of treatment. Luspatercept has also proven effective for patients with lower-risk myelodysplastic syndromes (MDS), a similar condition, by raising hemoglobin levels and reducing the need for blood transfusions. Most side effects are mild and manageable, making it a promising option for improving blood cell levels in these conditions. ^{1 4 5 6 7}

Who Is on the Research Team?

Pinkal Desai, MD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06788691

Luspatercept for Clonal Cytopenias of Uncertain Significance 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 ...

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

Treatment patterns and outcomes with luspatercept in ... Of the 6 ESA‐naive patients who were evaluable for mHI‐E, 83.3% (n = 5) achieved mHI‐E during weeks 1–24 of luspatercept treatment. Most patients among the ESA‐ ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/6730/528928/Long-Term-Real-World-Follow-up-Study-of

Long-Term Real-World Follow-up Study of Luspatercept for ... Luspatercept shows effective results in lower-risk MDS (LR-MDS) patients in a phase 3 study. However, the real-world data of luspatercept ...

4. jcto.weill.cornell.edu jcto.weill.cornell.edu/open_clinical_trials/efficacy-of-luspatercept-in-clonal-cytopenias-of-uncertain-significance

Efficacy of Luspatercept In Clonal Cytopenias of Uncertain ... The purpose of this study is to learn whether luspatercept is successful in improving blood counts in patients with clonal cytopenias of uncertain significance ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124095399

Safety and Efficacy of Luspatercept in Low-Risk ... Conclusions: Luspatercept was safe and effectiveive in people with low-risk MDNs with anaemia. Most adverse events were low-grade and mangeable.

6. 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 ... After 3 years of minimal follow-up, luspatercept safety profile was consistent with previous studies; no new safety signals identified. Subjects ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK595406/

Clinical Review - Luspatercept (Reblozyl) - NCBI - NIH Serious adverse events were reported by 31.4% of patients in the luspatercept treatment group and 30.3% of patients in the placebo group. The most common ...