Luspatercept for Myelofibrosis

(INDEPENDENCE Trial)

Not currently recruiting at 404 trial locations

Overseen By First line of the email MUST contain the NCT# and Site #.

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Celgene

Must be taking: JAK2 inhibitors

Must not be taking: Hydroxyurea, Immunomodulatory compounds

Disqualifiers: Uncontrolled hypertension, Prior malignancies, HIV, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if Luspatercept, a treatment for anemia, can benefit individuals with myelofibrosis who experience anemia and require regular blood transfusions. Researchers will compare Luspatercept to a placebo to assess its effectiveness and safety when used alongside a JAK2 inhibitor, a standard treatment for this condition. Participants must have been on a stable dose of a JAK2 inhibitor for at least 32 weeks and need regular blood transfusions due to symptoms like fatigue or shortness of breath. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you must be on a stable dose of a JAK2 inhibitor for at least 16 weeks before and 24 weeks after joining the study. Some medications like hydroxyurea and certain immunomodulatory drugs must be stopped 8 weeks before starting the trial.

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

Research has shown that luspatercept is generally well-tolerated by people with myelofibrosis. In earlier studies, patients with this condition experienced improvements in anemia (low red blood cell count) and required fewer blood transfusions while taking luspatercept. The safety profile of luspatercept—how well people handle the treatment without serious side effects—matched findings from past research. This indicates that the types and levels of side effects were consistent with those already known. While every treatment can have side effects, past data suggest that serious issues are uncommon with luspatercept. ^{1 2 3 4 5}

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

Unlike the standard treatments for myelofibrosis, which often focus on managing symptoms and improving blood flow, Luspatercept is unique because it targets a different aspect of the disease. Researchers are excited about Luspatercept because it works by enhancing late-stage red blood cell production, which could directly address anemia, a common and debilitating issue for myelofibrosis patients. This mechanism offers a novel approach compared to current therapies, potentially providing better management of anemia and improving quality of life. Additionally, Luspatercept is administered via subcutaneous injection every three weeks, which may offer a more convenient treatment schedule for patients.

What evidence suggests that Luspatercept might be an effective treatment for Myelofibrosis?

Research has shown that Luspatercept, which participants in this trial may receive, offers promising results for anemia in people with myelofibrosis. Studies have found that Luspatercept can reduce the need for red blood cell transfusions, a common issue for these patients. In earlier trials, patients experienced significant improvement in anemia symptoms. The treatment also demonstrated safety, with consistent results across different studies. These findings suggest that Luspatercept could be an effective option for managing anemia in myelofibrosis. ^{1 2 3 4 6}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

Adults diagnosed with Myelofibrosis associated with a myeloproliferative neoplasm, on stable JAK2 inhibitor therapy, needing regular blood transfusions due to anemia. Participants must have adequate organ function and not be pregnant or breastfeeding. They should agree to contraception if of childbearing potential and not have other significant health issues that could interfere with the study.

Inclusion Criteria

Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.

If you are sexually active with the opposite gender, you must agree to use effective contraception without interruption during the study and for 12 weeks after the study ends. If you choose not to use contraception, you must commit to not having any sexual contact and have it documented every month.

I am a male willing to use contraception or practice abstinence during and after the study for 12 weeks.

Exclusion Criteria

I have not had a major bleeding event in the last 6 months.

Subject with any of the following laboratory abnormalities at screening: Neutrophils: < 1 x 109/L, WBC: > 100 x 109/L, Platelets: not < 25 x 109/L or > 1000 x 109/L, Peripheral blood myeloblasts:> 5%, Estimated glomerular filtration rate:< 40 mL/min/1.73 m2, AST or ALT:> 3.0 x ULN, Direct bilirubin: ≥ 2 x ULN.

My heart condition is not well-managed, and my heart's pumping ability is weak.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Luspatercept or placebo via subcutaneous injection every 3 weeks during the Blinded Core Treatment Period, followed by a Day 169 Response Assessment and potential crossover to Open-label Extension Treatment Period

24 weeks

8 visits (in-person)

Blinded Extension Treatment

Continuation of treatment for participants showing clinical benefit, with the option to unblind for those not benefiting

Up to 3 years

Open-label Extension

Participants may opt into continuation of treatment with Luspatercept long-term after unblinding

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

42 days post last dose

What Are the Treatments Tested in This Trial?

Interventions

• Luspatercept
• Placebo

Trial Overview The trial is testing Luspatercept (ACE-536) against a placebo in subjects who are anemic as part of their myelofibrosis condition while already taking JAK2 inhibitors. The study includes several phases: initial treatment, response assessment, possible unblinding for non-responders, and follow-up.

How Is the Trial Designed?

Group I: Experimental Arm: Luspatercept (ACE-536) Experimental Treatment 1 Intervention

Luspatercept will be given to participants via subcutaneous injection (administered on Day 1 of each 21-day treatment cycle)

Group II: Control Arm: Placebo Placebo Group 1 Intervention

Placebo starting dose with volume equivalent to experimental arm subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle)

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?

Celgene

Lead Sponsor

Trials

649

Recruited

130,000+

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Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Citations

1. news.bms.com news.bms.com/news/details/2025/Bristol-Myers-Squibb-Announces-Topline-Results-from-Phase-3-INDEPENDENCE-Trial-for-Reblozyl-luspatercept-aamt-in-Adult-Patients-with-Myelofibrosis-Associated-Anemia/default.aspx

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. 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 ... In patients with myelofibrosis, luspatercept improved anemia and transfusion burden across cohorts; the safety profile was consistent with ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04717414

Study Details | NCT04717414 | An Efficacy and Safety ... The purpose of this Phase 3 study is to evaluate the efficacy and safety of Luspatercept compared with placebo in subjects with myeloproliferative neoplasm ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38820422/

Safety and efficacy of luspatercept for the treatment ... In patients with myelofibrosis, luspatercept improved anemia and transfusion burden across cohorts; the safety profile was consistent with previous studies.

5. asco.org asco.org/abstracts-presentations/ABSTRACT401610

Results from the ACE-536-MF-001 study. Conclusions: In pts with MF, the safety profile of LUSPA was consistent with previous studies and efficacy results showed promising improvements in anemia and ...

6. hematologyadvisor.com hematologyadvisor.com/news/mixed-results-for-luspatercept-in-patients-with-myelofibrosis-associated-anemia/

Mixed Results for Luspatercept in Patients With ... Additionally, more patients in the luspatercept group achieved at least a 50% reduction (and by ≥4 RBC units) in RBC transfusion burden and a ...