Phase 3 Study of Pelabresib (CPI-0610) in Myelofibrosis (MF) (MANIFEST-2)

Phase 3

Active, not recruiting

• Conditions: Myelofibrosis; Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis
• Interventions: Drug: Pelabresib; Drug: Ruxolitinib; Drug: Placebo

• Registration Number: NCT04603495
• Lead Sponsor: Constellation Pharmaceuticals

Brief Summary

A Phase 3, randomized, blinded study comparing pelabresib (CPI-0610) and ruxolitinib with placebo and ruxolitinib in myelofibrosis (MF) patients that have not been previously treated with Janus kinase inhibitors (JAKi). Pelabresib is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-10-20
• Study First Submitted QC: 2020-10-21
• Study First Posted: 2020-10-26
• Study Start: 2021-04-09
• Primary Completion: 2023-08-23
• Results First Submitted: 2024-08-23
• Status Verified: 2024-10
• Results First Submitted QC: 2024-10-25
• Last Update Submitted: 2024-10-25
• Results First Posted: 2024-10-28
• Last Update Posted: 2024-10-28
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 430

Inclusion Criteria

• Aged ≥ 18 years
• Confirmed diagnosis of myelofibrosis (primary, post-polycythemia vera, or post essential thrombocythemia)
• Adequate hematologic, renal, and hepatic function
• Have at least 2 symptoms with an average score ≥ 3 or an average total score of ≥ 10 over the 7-day period prior to randomization using the MFSAF v4.0
• Prognostic risk-factor score of Intermediate-1 or higher per Dynamic International Prognostic Scoring System (DIPSS) scoring system
• Spleen volume of ≥ 450 cm^3
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

Exclusion Criteria

• Splenectomy or splenic irradiation in the previous 6 months
• Chronic or active conditions and/or concomitant medication use that would prohibit treatment
• Had prior treatment with any JAKi or BET inhibitor for treatment of a myeloproliferative neoplasm

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pelabresib + ruxolitinib	Pelabresib	Pelabresib monohydrate tablets + ruxolitinib phosphate tablets
Pelabresib + ruxolitinib	Ruxolitinib	Pelabresib monohydrate tablets + ruxolitinib phosphate tablets
Placebo + ruxolitinib	Ruxolitinib	Matching placebo tablets + ruxolitinib phosphate tablets
Placebo + ruxolitinib	Placebo	Matching placebo tablets + ruxolitinib phosphate tablets

Primary Outcome Measures

Name	Time	Method
Number of Participants With Splenic Response by Central Reads at Week 24	24 weeks of treatment	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) or computerized tomography (CT), and assessed by blinded central radiology read at Week 24.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With TSS50 Response at Week 24	24 weeks of treatment	A key secondary endpoint of the study is Total Symptom Score (TSS) response, defined as a ≥50% decrease from baseline in TSS as measured by the Myelofibrosis Symptom Assessment Form v4.0, which equals the sum of the 7 individual item responses on the 0-10 scale, with a possible total daily score that may range from 0 to 70, at Week 24. A higher Total Symptom Score indicates a higher disease burden and thus a worse outcome.; Baseline TSS is calculated as the average of non-missing daily total symptom scores over the 7- day period prior to day of randomization. The TSS for a treatment week is the average of non-missing daily total symptom scores over that week. However, the weekly TSS will be considered missing if there are less than 4 daily total symptom scores available for that week.
Total Symptom Score Absolute Change From Baseline to Week 24	24 weeks of treatment	A key secondary endpoint of the study is the absolute change in Total Symptom Score (TSS) at Week 24 compared to baseline as measured by the Myelofibrosis Symptom Assessment Form v4.0, which equals the sum of the 7 individual item responses on the 0-10 scale, with a possible total daily score that may range from 0 to 70. A higher TSS indicates a higher disease burden and thus a worse outcome.; Baseline TSS is calculated as the average of non-missing daily total symptom scores over the 7- day period prior to day of randomization. The TSS for a treatment week is the average of non-missing daily total symptom scores over that week. However, the weekly TSS will be considered missing if there are less than 4 daily total symptom scores available for that week.

Trial Locations

Locations (156)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Ironwood Physicians P.C. dba Ironwood Cancer and Research Centers; 🇺🇸 Chandler, Arizona, United States

UC San Diego Moores Cancer Center; 🇺🇸 La Jolla, California, United States

USC/Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

UCLA Medical Center; 🇺🇸 Los Angeles, California, United States

Yale University School of Medicine; 🇺🇸 New Haven, Connecticut, United States

Mayo Clinic; 🇺🇸 Jacksonville, Florida, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Decatur Memorial Hospital Cancer Care Center of Decatur/Cancer Care Specialists of IL; 🇺🇸 Decatur, Illinois, United States

Franciscan Health/Indiana blood and Marrow Transplantation; 🇺🇸 Indianapolis, Indiana, United States

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