Pelabresib for Myelofibrosis
(MANIFEST-2 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
Who Is on the Research Team?
Novartis Pharmaceuticals
Principal Investigator
Novartis Pharmaceuticals
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
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive pelabresib and ruxolitinib or placebo and ruxolitinib for 24 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
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?
2
Treatment groups
Experimental Treatment
Active Control
Pelabresib monohydrate tablets + ruxolitinib phosphate tablets
Matching placebo tablets + ruxolitinib phosphate tablets
Find a Clinic Near You
Who Is Running the Clinical Trial?
Novartis Pharmaceuticals
Lead Sponsor
Dr. Vas Narasimhan
Novartis Pharmaceuticals
Chief Executive Officer since 2018
MD from Harvard Medical School
Dr. Shreeram Aradhye
Novartis Pharmaceuticals
Chief Medical Officer since 2021
MD
Constellation Pharmaceuticals
Lead Sponsor
Published Research Related to This Trial
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 ...
4.
hematologyadvisor.com
hematologyadvisor.com/news/myelofibrosis-trial-pelabresib-ruxolitinib-combo-therapy-risk/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 ...
7.
ashpublications.org
ashpublications.org/blood/article/144/Supplement%201/3178/529578/Updated-Results-from-the-Phase-3-Manifest-2-StudyUpdated 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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