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)
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
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:
|
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:
|
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:
|
Outcome Measures
Primary Outcome Measures
- Incidence of adverse events (AEs) [Up to 52 months]
- Incidence of serious adverse events (SAEs) [Up to 52 months]
- Incidence of AEs meeting protocol-defined dose-limiting toxicity (DLT) criteria [Up to 26 months]
- Incidence of AEs leading to discontinuation [Up to 52 months]
- Incidence of death [Up to 52 months]
Secondary Outcome Measures
- Spleen volume reduction (SVR) at end of Cycle 6 assessed by Blinded Independent Central Review (BICR) [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 [Up to 168 days]
- Symptom response rate (SRR) based on total symptom score (TSS) measured by Myelofibrosis Symptom Assessment Form (MFSAF) [Up to 168 days]
- Additional measures based on TSS measured by MFSAF [Up to 168 days]
- For transfusion independent (TI), proportion of participants having ≥ 2.0 g/dL hemoglobin (Hgb) increase over baseline [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 [Up to 24 months]
- Summary of pharmacokinetics (PK) parameters: maximum observed concentration (Cmax) [Up to 56 days]
- Summary of PK parameters: time of maximum observed concentration (Tmax) [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)) [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 [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 [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 [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 [Up to 24 months]
Eligibility Criteria
Criteria
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.- CA011-023
- 2020-002071-35