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)

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04817007
Collaborator
(none)
192
30
6
73.1
6.4
0.1

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
192 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Mar 23, 2021
Anticipated Primary Completion Date :
Apr 14, 2025
Anticipated Study Completion Date :
Apr 26, 2027

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part 1A: BMS-986158 + Ruxolitinib

Drug: BMS-986158
Specified dose on specified days

Drug: Ruxolitinib
Specified dose on specified days
Other Names:
  • Jakafi®
  • Experimental: Part 1B: BMS-986158 + Fedratinib

    Drug: BMS-986158
    Specified dose on specified days

    Drug: Fedratinib
    Specified dose on specified days

    Experimental: Part 2A1: BMS-986158 + Ruxolitinib

    Drug: BMS-986158
    Specified dose on specified days

    Drug: Ruxolitinib
    Specified dose on specified days
    Other Names:
  • Jakafi®
  • Experimental: Part 2B1: BMS-986158 + Fedratinib

    Drug: BMS-986158
    Specified dose on specified days

    Drug: Fedratinib
    Specified dose on specified days

    Experimental: Part 2B2: BMS-986158 Mono and/or (BMS-986158 + Fedratinib), if applicable

    Drug: BMS-986158
    Specified dose on specified days

    Drug: Fedratinib
    Specified dose on specified days

    Experimental: Part 2A2 Add-On: BMS-986158 + Ruxolitinib

    Drug: BMS-986158
    Specified dose on specified days

    Drug: Ruxolitinib
    Specified dose on specified days
    Other Names:
  • Jakafi®
  • Outcome Measures

    Primary Outcome Measures

    1. Incidence of adverse events (AEs) [Up to 52 months]

    2. Incidence of serious adverse events (SAEs) [Up to 52 months]

    3. Incidence of AEs meeting protocol-defined dose-limiting toxicity (DLT) criteria [Up to 26 months]

    4. Incidence of AEs leading to discontinuation [Up to 52 months]

    5. Incidence of death [Up to 52 months]

    Secondary Outcome Measures

    1. Spleen volume reduction (SVR) at end of Cycle 6 assessed by Blinded Independent Central Review (BICR) [Up to 168 days]

    2. Response rate defined as proportion of participants with SVR ≥ 35% by MRI (preferred) or CT (if MRI is contraindicated) assessed by BICR [Up to 168 days]

    3. Symptom response rate (SRR) based on total symptom score (TSS) measured by Myelofibrosis Symptom Assessment Form (MFSAF) [Up to 168 days]

    4. Additional measures based on TSS measured by MFSAF [Up to 168 days]

    5. For transfusion independent (TI), proportion of participants having ≥ 2.0 g/dL hemoglobin (Hgb) increase over baseline [Up to 24 months]

    6. 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 [Up to 24 months]

    7. Summary of pharmacokinetics (PK) parameters: maximum observed concentration (Cmax) [Up to 56 days]

    8. Summary of PK parameters: time of maximum observed concentration (Tmax) [Up to 56 days]

    9. Summary of PK parameters: area under the concentration-time curve from time zero to the time of the last quantifiable concentration ((AUC (0-T)) [Up to 56 days]

    10. 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 [6 month and 12 month]

      International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Spleen and disease progression free survival (SDPFS)

    11. 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 [6 month and 12 month]

    12. 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 [Up to 24 months]

    13. For transfusion dependent (TD), proportion of participants becoming Tl as measured by the absence of hydroxyurea over any consecutive 12-week period [Up to 24 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Local Institution San Diego California United States 92037-0820
    2 Tulane University School of Medicine New Orleans Louisiana United States 70112
    3 Local Institution Worcester Massachusetts United States 01655
    4 Local Institution Ann Arbor Michigan United States 48109
    5 Local Institution San Antonio Texas United States 78229
    6 Local Institution Blacktown New South Wales Australia 2148
    7 Local Institution Wollongong New South Wales Australia 2500
    8 Local Institution - 0007 East Melbourne Victoria Australia 3002
    9 Local Institution Heidelberg Victoria Australia 3084
    10 The Perth Blood Institute - West Perth West Perth Western Australia Australia 6005
    11 Local Institution Brest France 29609
    12 Institut Paoli-Calmettes-Hematology Marseille France 13273
    13 Centre Hospitalier Universitaire de Nice - Hôpital l'Archet-Hematology Nice France 06002
    14 Local Institution - 0011 Paris France 75010
    15 Gustave Roussy-DITEP Villejuif France 94805
    16 Local Institution - 0040 Chemnitz Sachsen Germany 09116
    17 Local Institution Essen Germany 45147
    18 Local Institution Halle (Saale) Germany 06120
    19 Local Institution - 0016 Jerusalem Israel 9112001
    20 Local Institution - 0018 Petah-Tikva Israel 4910021
    21 Local Institution Ramat Gan Israel 52621
    22 Local Institution Tel Aviv Israel 6423906
    23 Local Institution Bologna Italy 40138
    24 Local Institution - 0002 Brescia Italy 25123
    25 Local Institution Firenze Italy 50134
    26 Local Institution Verona Italy 37134
    27 Local Institution Badalona Spain 08916
    28 Local Institution - 0026 Madrid Spain 28041
    29 Local Institution Salamanca Spain 37007
    30 Local Institution Santander Spain 39008

    Sponsors and Collaborators

    • Bristol-Myers Squibb

    Investigators

    • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT04817007
    Other Study ID Numbers:
    • CA011-023
    • 2020-002071-35
    First Posted:
    Mar 25, 2021
    Last Update Posted:
    Aug 3, 2022
    Last Verified:
    Aug 1, 2022
    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
    Keywords provided by Bristol-Myers Squibb
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 3, 2022