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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT04603495
Registration number
NCT04603495
Ethics application status
Date submitted
20/10/2020
Date registered
26/10/2020
Titles & IDs
Public title
Phase 3 Study of Pelabresib (CPI-0610) in Myelofibrosis (MF) (MANIFEST-2)
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Scientific title
A Phase 3, Randomized, Double-blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAKi Treatment Naive MF Patients
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Secondary ID [1]
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2020-001989-10
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Secondary ID [2]
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CPI 0610-04
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Universal Trial Number (UTN)
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Trial acronym
MANIFEST-2
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Myelofibrosis
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Primary Myelofibrosis
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Post-polycythemia Vera Myelofibrosis
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Post-essential Thrombocythemia Myelofibrosis
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Condition category
Condition code
Blood
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0
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Haematological diseases
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Blood
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0
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0
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Other blood disorders
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Musculoskeletal
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0
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0
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Other muscular and skeletal disorders
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Human Genetics and Inherited Disorders
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0
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Other human genetics and inherited disorders
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Cancer
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0
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Leukaemia - Chronic leukaemia
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Pelabresib
Treatment: Drugs - Ruxolitinib
Treatment: Drugs - Placebo
Experimental: Pelabresib + ruxolitinib - Pelabresib monohydrate tablets + ruxolitinib phosphate tablets
Active comparator: Placebo + ruxolitinib - Matching placebo tablets + ruxolitinib phosphate tablets
Treatment: Drugs: Pelabresib
Double-blind treatment (pelabresib or matching placebo) will be administered daily for 14 consecutive days followed by a 7-day break, which is considered 1 cycle of treatment (1 cycle = 21 days).
Pelabresib is a small molecule inhibitor of BET proteins with a novel mechanism of action and potential for disease-modifying effects in MF.
Treatment: Drugs: Ruxolitinib
Ruxolitinib is a JAK inhibitor and a current, approved treatment option for MF.
Treatment: Drugs: Placebo
Placebo tablets are designed to match pelabresib tablets. Each placebo tablet contains no active pharmaceutical ingredient and is visibly identical to experimental drug in size, shape, and packaging. Placebo dosing follows the same dosing conventions as pelabresib.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Splenic response at Week 24
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Assessment method [1]
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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), at Week 24.
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Timepoint [1]
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24 weeks of treatment
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Secondary outcome [1]
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Total Symptom Score absolute change from baseline to Week 24
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Assessment method [1]
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A key secondary endpoint of the study is the absolute change in Total Symptom Score at Week 24 compared to baseline as measured by the Myelofibrosis Symptom Assessment Form v4.0. A higher Total Symptom Score indicates a higher disease burden and thus a worse outcome.
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Timepoint [1]
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24 weeks of treatment
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Secondary outcome [2]
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Total Symptom Score response at Week 24
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Assessment method [2]
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A key secondary endpoint of the study is Total Symptom Score response, defined as a =50% decrease from baseline in Total Symptom Score as measured by the Myelofibrosis Symptom Assessment Form v4.0, at Week 24. A higher Total Symptom Score indicates a higher disease burden and thus a worse outcome.
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Timepoint [2]
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24 weeks of treatment
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Eligibility
Key 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
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Active, not recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
9/04/2021
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
1/12/2027
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Actual
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Sample size
Target
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Accrual to date
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Final
430
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Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC
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Recruitment hospital [1]
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Icon Cancer Centre - Brisbane
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Royal Adelaide Hospital - Adelaide
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Monash Health - Clayton
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Peninsula Private Hospital Clinical Trials Unit - Frankston
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USC Clinical Trials Centre Sunshine Coast Haematology and Oncology Clinic - Buderim
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Recruitment hospital [6]
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One Clinical Research PTY LTD - Nedlands
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4101 - Brisbane
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5000 - Adelaide
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3168 - Clayton
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3199 - Frankston
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QLD 4556 - Buderim
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6009 - Nedlands
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Name
Constellation Pharmaceuticals
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Summary
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.
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Trial website
https://clinicaltrials.gov/study/NCT04603495
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Trial related presentations / publications
Mascarenhas J, Kremyanskaya M, Patriarca A, Harrison C, Bose P, Rampal RK, Palandri F, Devos T, Passamonti F, Hobbs G, Talpaz M, Vannucchi A, Kiladjian JJ, Verstovsek S, Hoffman R, Salama ME, Chen D, Taverna P, Chang A, Colak G, Klein S, Gupta V. MPN-375 BET Inhibitor Pelabresib (CPI-0610) Combined With Ruxolitinib in Patients With Myelofibrosis - JAK Inhibitor-Naie or With Suboptimal Response to Ruxolitinib - Preliminary Data From the MANIFEST Study. Clin Lymphoma Myeloma Leuk. 2022 Oct;22 Suppl 2:S335-S336. doi: 10.1016/S2152-2650(22)01456-2. Harrison CN, Gupta VK, Gerds AT, Rampal R, Verstovsek S, Talpaz M, Kiladjian JJ, Mesa R, Kuykendall AT, Vannucchi AM, Palandri F, Grosicki S, Devos T, Jourdan E, Wondergem MJ, Al-Ali HK, Buxhofer-Ausch V, Alvarez-Larran A, Patriarca A, Kremyanskaya M, Mead AJ, Akhani S, Sheikine Y, Colak G, Mascarenhas J. Phase III MANIFEST-2: pelabresib + ruxolitinib vs placebo + ruxolitinib in JAK inhibitor treatment-naive myelofibrosis. Future Oncol. 2022 Sep;18(27):2987-2997. doi: 10.2217/fon-2022-0484. Epub 2022 Aug 11.
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Public notes
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Contacts
Principal investigator
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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No/undecided IPD sharing reason/comment
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What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT04603495