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A Study to Assess the Safety and Tolerability of BMS-986158 Alone and in Combination With Either Ruxolitinib or Fedratinib in Participants With Blood Cancer (Myelofibrosis)

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ClinicalTrials.gov Identifier: NCT04817007
Recruitment Status : Recruiting
First Posted : March 25, 2021
Last Update Posted : August 3, 2022
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE March 18, 2021
First Posted Date  ICMJE March 25, 2021
Last Update Posted Date August 3, 2022
Actual Study Start Date  ICMJE March 23, 2021
Estimated Primary Completion Date April 14, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 24, 2021)
  • Incidence of adverse events (AEs) [ Time Frame: Up to 52 months ]
  • Incidence of serious adverse events (SAEs) [ Time Frame: Up to 52 months ]
  • Incidence of AEs meeting protocol-defined dose-limiting toxicity (DLT) criteria [ Time Frame: Up to 26 months ]
  • Incidence of AEs leading to discontinuation [ Time Frame: Up to 52 months ]
  • Incidence of death [ Time Frame: Up to 52 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 18, 2022)
  • Spleen volume reduction (SVR) at end of Cycle 6 assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to 168 days ]
  • Response rate defined as proportion of participants with SVR ≥ 35% by MRI (preferred) or CT (if MRI is contraindicated) assessed by BICR [ Time Frame: Up to 168 days ]
  • Symptom response rate (SRR) based on total symptom score (TSS) measured by Myelofibrosis Symptom Assessment Form (MFSAF) [ Time Frame: Up to 168 days ]
  • Additional measures based on TSS measured by MFSAF [ Time Frame: Up to 168 days ]
  • For transfusion independent (TI), proportion of participants having ≥ 2.0 g/dL hemoglobin (Hgb) increase over baseline [ Time Frame: Up to 24 months ]
  • For transfusion dependent (TD), proportion of participants becoming TI as measured by the absence of red blood cell (RBC) transfusions over any consecutive 12-week period [ Time Frame: Up to 24 months ]
  • Summary of pharmacokinetics (PK) parameters: maximum observed concentration (Cmax) [ Time Frame: Up to 56 days ]
  • Summary of PK parameters: time of maximum observed concentration (Tmax) [ Time Frame: Up to 56 days ]
  • Summary of PK parameters: area under the concentration-time curve from time zero to the time of the last quantifiable concentration ((AUC (0-T)) [ Time Frame: Up to 56 days ]
  • Time from Dose 1, Day 1 to death due to any reason or disease progression (per modified IWG-MRT 2013) assessed by BICR: SDPFS rates at 6 months and 12 months [ Time Frame: 6 month and 12 month ]
    International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Spleen and disease progression free survival (SDPFS)
  • Time from Dose 1, Day 1 to death due to any reason or disease progression (per modified IWG-MRT 2013) assessed by BICR: median SDPFS at 6 months and 12 months [ Time Frame: 6 month and 12 month ]
  • For transfusion dependent (TD), proportion of participants becoming Tl as measured by the absence of erythropoiesis stimulating agents (ESA) over any consecutive 12-week period [ Time Frame: Up to 24 months ]
  • For transfusion dependent (TD), proportion of participants becoming Tl as measured by the absence of hydroxyurea over any consecutive 12-week period [ Time Frame: Up to 24 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 24, 2021)
  • Spleen volume reduction (SVR) at end of Cycle 6 assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to 52 months ]
  • Response rate defined as proportion of participants with SVR ≥ 35% by MRI (preferred) or CT (if MRI is contraindicated) assessed by BICR [ Time Frame: Up to 52 months ]
  • Symptom response rate (SRR) based on total symptom score (TSS) measured by Myelofibrosis Symptom Assessment Form (MFSAF) [ Time Frame: Up to 168 days ]
  • Additional measures based on TSS measured by MFSAF [ Time Frame: Up to 168 days ]
  • For transfusion independent (TI), proportion of participants having ≥ 2.0 g/dL hemoglobin (Hgb) increase over baseline [ Time Frame: Up to 24 months ]
  • For transfusion dependent (TD), proportion of participants becoming TI as measured by the absence of red blood cell (RBC) transfusions over any consecutive 12-week period [ Time Frame: Up to 24 months ]
  • Summary of pharmacokinetics (PK) parameters: maximum observed concentration (Cmax) [ Time Frame: Up to 56 days ]
  • Summary of PK parameters: time of maximum observed concentration (Tmax) [ Time Frame: Up to 56 days ]
  • Summary of PK parameters: area under the concentration-time curve from time zero to the time of the last quantifiable concentration ((AUC (0-T)) [ Time Frame: Up to 56 days ]
  • Time from Dose 1, Day 1 to death due to any reason or disease progression (per modified IWG-MRT 2013) assessed by BICR: SDPFS rates at 6 months and 12 months [ Time Frame: 6 month and 12 month ]
    International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Spleen and disease progression free survival (SDPFS)
  • Time from Dose 1, Day 1 to death due to any reason or disease progression (per modified IWG-MRT 2013) assessed by BICR: median SDPFS at 6 months and 12 months [ Time Frame: 6 month and 12 month ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Assess the Safety and Tolerability of BMS-986158 Alone and in Combination With Either Ruxolitinib or Fedratinib in Participants With Blood Cancer (Myelofibrosis)
Official Title  ICMJE A Phase 1b/2 Study of BMS-986158 Monotherapy and in Combination With Either Ruxolitinib or Fedratinib in Participants With DIPSS-Intermediate or High Risk Myelofibrosis
Brief Summary The purpose of this study is to assess the safety, tolerability, and efficacy of BMS-986158 alone and in combination with either Ruxolitinib or Fedratinib in participants with Dynamic International Prognostic Scoring System (DIPSS)-intermediate or high risk blood cancer. Part 1 consists of BMS-986158 in combination with either Ruxolitinib or Fedratinib and Part 2 consists of BMS-986158 in combination with either Ruxolitinib or Fedratinib and BMS-986158 alone.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Myelofibrosis
Intervention  ICMJE
  • Drug: BMS-986158
    Specified dose on specified days
  • Drug: Ruxolitinib
    Specified dose on specified days
    Other Name: Jakafi®
  • Drug: Fedratinib
    Specified dose on specified days
Study Arms  ICMJE
  • Experimental: Part 1A: BMS-986158 + Ruxolitinib
    Interventions:
    • Drug: BMS-986158
    • Drug: Ruxolitinib
  • Experimental: Part 1B: BMS-986158 + Fedratinib
    Interventions:
    • Drug: BMS-986158
    • Drug: Fedratinib
  • Experimental: Part 2A1: BMS-986158 + Ruxolitinib
    Interventions:
    • Drug: BMS-986158
    • Drug: Ruxolitinib
  • Experimental: Part 2B1: BMS-986158 + Fedratinib
    Interventions:
    • Drug: BMS-986158
    • Drug: Fedratinib
  • Experimental: Part 2B2: BMS-986158 Mono and/or (BMS-986158 + Fedratinib), if applicable
    Interventions:
    • Drug: BMS-986158
    • Drug: Fedratinib
  • Experimental: Part 2A2 Add-On: BMS-986158 + Ruxolitinib
    Interventions:
    • Drug: BMS-986158
    • Drug: Ruxolitinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 18, 2022)
192
Original Estimated Enrollment  ICMJE
 (submitted: March 24, 2021)
156
Estimated Study Completion Date  ICMJE April 26, 2027
Estimated Primary Completion Date April 14, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of primary myelofibrosis (PMF), post-essential thrombocythemia (ET) or post-polycythemia vera (PV) myelofibrosis
  • Treatment-related toxicities from prior therapy resolved to Grade 1 or pre-treatment baseline or determined to be irreversible prior to study treatment
  • Must agree to follow specific methods of contraception, if applicable

Exclusion Criteria:

  • Women who are pregnant or breastfeeding at screening
  • Any significant acute or uncontrolled chronic medical illness

Other protocol-defined inclusion/exclusion criteria apply

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: BMS Study Connect Contact Center www.BMSStudyConnect.com 855-907-3286 Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT # and Site #.
Listed Location Countries  ICMJE Australia,   France,   Germany,   Israel,   Italy,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04817007
Other Study ID Numbers  ICMJE CA011-023
2020-002071-35 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Bristol-Myers Squibb
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Bristol-Myers Squibb
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date August 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP