430 Participants Needed

Pelabresib for Myelofibrosis

(MANIFEST-2 Trial)

Recruiting at 249 trial locations
DJ
MD
MI
Overseen ByMedical Information
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: Constellation Pharmaceuticals
Must be taking: Ruxolitinib
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, pelabresib, for individuals with myelofibrosis, a rare bone marrow disorder that disrupts blood cell production. The trial compares the combination of pelabresib and ruxolitinib to a placebo with ruxolitinib to determine its effectiveness. Individuals with myelofibrosis who have not previously received certain inhibitors may be suitable candidates, especially if they experience symptoms affecting daily life. Researchers will monitor participants' health to assess whether pelabresib can manage their condition more effectively. 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.

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

The trial protocol does not specify if you need to stop your current medications, but it excludes those with medication use that would prohibit treatment. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that pelabresib, when combined with ruxolitinib, is generally safe for people with myelofibrosis. In a study involving 430 patients, researchers closely monitored the treatment's safety. Most patients tolerated the treatment well throughout the study. Although specific side effects were not detailed, the treatment's presence in a late-stage study suggests earlier research has already established its general safety for human use.12345

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

Pelabresib is unique because it offers a new approach to treating myelofibrosis by targeting bromodomain and extra-terminal (BET) proteins, which play a role in regulating genes involved in blood cell development and inflammation. Unlike the standard myelofibrosis treatments, which typically focus on inhibiting Janus kinase (JAK) pathways, pelabresib works differently, potentially reducing fibrosis and improving blood counts. Researchers are excited about pelabresib because it could enhance the efficacy of existing treatments like ruxolitinib, potentially leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for myelofibrosis?

This trial will compare the combination of pelabresib with ruxolitinib to a placebo with ruxolitinib for treating myelofibrosis. Research has shown that combining pelabresib with ruxolitinib may help treat myelofibrosis. In one study, 18.8% of patients taking both drugs experienced at least one level of improvement in their condition, compared to 11.2% of those taking only ruxolitinib and a placebo. Additionally, 36.8% of patients no longer needed blood transfusions, achieving transfusion independence. Improvement in bone marrow health, indicating disease improvement, was observed in 35% of patients. The combination also significantly reduced spleen size by 35%, which is important for managing symptoms. These findings suggest that pelabresib could be a helpful addition to standard myelofibrosis treatment.34567

Are You a Good Fit for This Trial?

This trial is for adults with myelofibrosis, including those who developed it from polycythemia vera or essential thrombocythemia. Participants must have certain symptoms and spleen enlargement, be in a specific risk category, and have good organ function. They can't join if they've had their spleen removed recently or used JAKi/BET inhibitors before.

Inclusion Criteria

I have been diagnosed with myelofibrosis.
My blood, kidney, and liver functions are all within normal ranges.
My condition is rated Intermediate-1 or higher on the DIPSS scale.
See 3 more

Exclusion Criteria

I have had my spleen removed or treated with radiation in the last 6 months.
I don't have any health conditions or take medications that would stop me from receiving treatment.
I have been treated with JAKi or BET inhibitors for a blood disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pelabresib and ruxolitinib or placebo and ruxolitinib for 24 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Pelabresib (CPI-0610)
Trial Overview The study tests Pelabresib (a BET protein inhibitor) combined with Ruxolitinib versus a placebo with Ruxolitinib in patients new to JAK inhibitor treatments. It's randomized and blinded, meaning participants are assigned by chance to either the test drug or placebo without knowing which one they receive.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Active Control
Group I: Pelabresib + ruxolitinibExperimental Treatment2 Interventions
Group II: Placebo + ruxolitinibActive Control2 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

Constellation Pharmaceuticals

Lead Sponsor

Trials
10
Recruited
1,500+

Published Research Related to This Trial

JAK inhibitors have significantly improved treatment options for myelofibrosis (MF) by alleviating symptoms, reducing spleen size, and enhancing quality of life, although they may lead to worsening blood cell counts (cytopenias).
Despite their benefits, JAK inhibitors do not stop disease progression or prevent the transformation to leukemia, and their impact on overall survival remains uncertain.
JAK inhibitors in the treatment of myelofibrosis.Levavi, H., Hoffman, R., Marcellino, BK.[2022]

Citations

Pelabresib plus ruxolitinib for JAK inhibitor-naive ...Improvement of at least one grade was observed in 18.8% (36 out of 192) of patients treated with pelabresib–ruxolitinib and in 11.2% (21 out of ...
P1018: UPDATED RESULTS FROM MANIFEST ARM 2 ...Transfusion independence was achieved in 36.8% of pts, and improvement in BM fibrosis, as a marker of disease modification, was observed in 35% ...
Paper: Updated Results from the Phase 3 Manifest-2 Study ...As of March 29, 2024, all pts assessed had been followed for ≥48 wks; 58.9% (126/214) and 62.0% (134/216) of pts continued on double-blind treatment in the PELA ...
Trial Results Support Use of Pelabresib and Ruxolitinib ...The primary outcome measure was a reduction in spleen volume of 35% or more from baseline at week 24. Key secondary outcome measures included ...
NCT04603495 | Phase 3 Study of Pelabresib (CPI-0610) in ...The primary endpoint of the study is splenic response, defined as a ≥35% reduction from baseline in spleen volume as measured by magnetic resonance imaging (MRI) ...
Updated safety and efficacy data from the phase 3 ...Results: As of Aug 31, 2023, 430 pts were randomized. At Wk 24, 65.9% (141/214) vs 35.2% (76/216) (p<0.001) of pts had an SVR35 response ...
Updated Results from the Phase 3 Manifest-2 Study of ...As of March 29, 2024, all pts assessed had been followed for ≥48 wks; 58.9% (126/214) and 62.0% (134/216) of pts continued on double-blind ...
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