Pelabresib for Myelofibrosis

(MANIFEST-2 Trial)

Recruiting at 205 trial locations

Overseen By Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Constellation Pharmaceuticals

Must be taking: Ruxolitinib

Must not be taking: JAK inhibitors, BET inhibitors

Disqualifiers: Splenectomy, Splenic irradiation, others

No Placebo Group All 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 Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

430 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new drug combination of pelabresib and ruxolitinib in patients with myelofibrosis who haven't tried certain treatments before. Pelabresib blocks harmful proteins, and ruxolitinib stops harmful signals to see if this combination works better.

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.

What data supports the effectiveness of the drug Pelabresib for treating myelofibrosis?

Research shows that Pelabresib, when combined with the standard drug ruxolitinib, may reduce spleen size and improve symptoms in patients with myelofibrosis more effectively than using ruxolitinib alone. This combination has shown promising results in early studies, suggesting it could be more effective than current treatments. ^{1 2 3 4 5}

Is Pelabresib safe for humans?

Pelabresib (CPI-0610) is being studied for its safety and effectiveness in treating myelofibrosis, often in combination with another drug called ruxolitinib. While the studies focus on its potential benefits, they also monitor for any side effects to ensure it is safe for human use. ^{1 2 3 4 6}

How is the drug Pelabresib different from other treatments for myelofibrosis?

Pelabresib (CPI-0610) is unique because it targets epigenetic modulation, which is different from the standard JAK inhibitors used for myelofibrosis. This approach offers a potential treatment option for patients who cannot use JAK inhibitors or for whom these drugs are ineffective. ^{7 8 9 10 11}

Eligibility Criteria

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.

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

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

Treatment Details

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.

Participant Groups

Group I: Pelabresib + ruxolitinib Experimental Treatment 2 Interventions

Pelabresib monohydrate tablets + ruxolitinib phosphate tablets

Group II: Placebo + ruxolitinib Active Control 2 Interventions

Matching placebo tablets + ruxolitinib phosphate tablets

Who Is Running the Clinical Trial?

Constellation Pharmaceuticals

Lead Sponsor

Trials

10

Recruited

1,500+

Findings from Research

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK inhibitors in the treatment of myelofibrosis. Levavi, H., Hoffman, R., Marcellino, BK.[2022]

References

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

MANIFEST: Pelabresib in Combination With Ruxolitinib for Janus Kinase Inhibitor Treatment-Naïve Myelofibrosis. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Phase III MANIFEST-2: pelabresib + ruxolitinib vs placebo + ruxolitinib in JAK inhibitor treatment-naive myelofibrosis. [2023]

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

Pelabresib (CPI-0610): An Exciting Novel Drug for the Treatment of Myelofibrosis. [2023]

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

Matching-adjusted indirect comparison of the pelabresib-ruxolitinib combination vs JAKi monotherapy in myelofibrosis. [2023]

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

PD-1 inhibition in advanced myeloproliferative neoplasms. [2022]

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

JAK inhibitors in the treatment of myelofibrosis. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Next Generation Therapeutics for the Treatment of Myelofibrosis. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Are we altering the natural history of primary myelofibrosis? [2015]

9. Norway pubmed.ncbi.nlm.nih.gov

[Primary myelofibrosis--pathogenesis, diagnosis and treatment]. [2021]

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

Metformin: An Old Dog with a New Trick? [2019]

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

Pirfenidone and Nintedanib for Treatment of Idiopathic Pulmonary Fibrosis. [2018]