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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)

Phase 1
Active, not recruiting
Conditions
Myelofibrosis
Interventions
Registration Number
NCT04817007
Lead Sponsor
Bristol-Myers Squibb
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 available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
216
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Part 2B1: BMS-986158 + FedratinibFedratinib-
Part 2A3: BMS-986158 + RuxolitinibBMS-986158-
Part 2A3: BMS-986158 + RuxolitinibRuxolitinib-
Part 1A: BMS-986158 + RuxolitinibBMS-986158-
Part 1A: BMS-986158 + RuxolitinibRuxolitinib-
Part 1B: BMS-986158 + FedratinibBMS-986158-
Part 1B: BMS-986158 + FedratinibFedratinib-
Part 2A1: BMS-986158 + RuxolitinibBMS-986158-
Part 2B1: BMS-986158 + FedratinibBMS-986158-
Part 2A1: BMS-986158 + RuxolitinibRuxolitinib-
Part 2B2: BMS-986158 Mono and/or (BMS-986158 + Fedratinib), if applicableFedratinib-
Part 2A2 Add-On: BMS-986158 + RuxolitinibRuxolitinib-
Part 2B2: BMS-986158 Mono and/or (BMS-986158 + Fedratinib), if applicableBMS-986158-
Part 2A2 Add-On: BMS-986158 + RuxolitinibBMS-986158-
Primary Outcome Measures
NameTimeMethod
Incidence of AEs meeting protocol-defined dose-limiting toxicity (DLT) criteriaUp to 26 months
Incidence of AEs leading to discontinuationUp to 52 months
Incidence of deathUp to 52 months
Incidence of adverse events (AEs)Up to 52 months
Incidence of serious adverse events (SAEs)Up to 52 months
Secondary Outcome Measures
NameTimeMethod
Spleen volume reduction (SVR) at end of Cycle 6 assessed by Blinded Independent Central Review (BICR)Up to 175 days
Response rate defined as proportion of participants with SVR ≥ 35% by MRI (preferred) or CT (if MRI is contraindicated and if CT is allowed by local guidelines) assessed by BICRUp to 175 days
SVR at end of Cycle 3 and 6 assessed by BICRUp to 175 days
Response rate defined as proportion of participants with SVR ≥ 25% by MRI (preferred) or CT (if MRI is contraindicated and if CT is allowed by local guidelines) assessed by BICRUp to 175 days
Symptom response rate (SRR) based on total symptom score (TSS) measured by Myelofibrosis Symptom Assessment Form (MFSAF)Up to 175 days
Additional measures based on TSS measured by MFSAFUp to 175 days

Trial Locations

Locations (53)

Local Institution - 0010

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Villejuif, France

Local Institution - 0069

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Newport Beach, California, United States

Local Institution - 0090

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Lake Mary, Florida, United States

Local Institution - 0043

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New Orleans, Louisiana, United States

Local Institution - 0038

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Worcester, Massachusetts, United States

Local Institution - 0033

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Ann Arbor, Michigan, United States

Local Institution - 0045

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Hackensack, New Jersey, United States

Local Institution - 0076

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Chapel Hill, North Carolina, United States

Local Institution - 0042

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Pittsburgh, Pennsylvania, United States

Local Institution - 0036

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Blacktown, New South Wales, Australia

Local Institution - 0032

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Wollongong, New South Wales, Australia

Local Institution - 0007

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East Melbourne, Victoria, Australia

Local Institution - 0006

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Heidelberg, Victoria, Australia

Local Institution - 0041

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Nedlands, Western Australia, Australia

Local Institution - 0015

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West Perth, Western Australia, Australia

Local Institution - 0030

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Brest, France

Local Institution - 0008

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Marseille, France

Local Institution - 0027

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Nice, France

Local Institution - 0011

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Paris, France

Local Institution - 0068

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Erding, Bayern, Germany

Local Institution - 0039

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Essen, Nordrhein-Westfalen, Germany

Local Institution - 0035

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Halle, Sachsen-Anhalt, Germany

Local Institution - 0040

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Chemnitz, Sachsen, Germany

Local Institution - 0050

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Lübeck, Schleswig-Holstein, Germany

Local Institution - 0061

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Chaidari, Attikí, Greece

Local Institution - 0047

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Thessaloniki, Thessaloníki, Greece

Local Institution - 0073

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Szeged, Csongrád, Hungary

Local Institution - 0072

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Nyiregyhaza, Szabolcs-Szatmár-Bereg, Hungary

Local Institution - 0075

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Budapest, Hungary

Local Institution - 0074

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Debrecen, Hungary

Local Institution - 0086

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Be'er Sheva, HaDarom, Israel

Local Institution - 0016

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Jerusalem, Israel

Local Institution - 0018

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Petah-Tikva, Israel

Local Institution - 0017

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Ramat Gan, Israel

Local Institution - 0019

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Tel Aviv, Israel

Local Institution - 0003

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Bologna, Italy

Local Institution - 0002

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Brescia, Italy

Local Institution - 0001

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Firenze, Italy

Local Institution - 0012

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Verona, Italy

Local Institution - 0049

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Seongnam, Kyǒnggi-do, Korea, Republic of

Local Institution - 0048

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Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of

Local Institution - 0053

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Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of

Local Institution - 0077

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Słupsk, Pomorskie, Poland

Local Institution - 0062

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Gdańsk, Poland

Local Institution - 0052

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Bucuresti, Cluj, Romania

Local Institution - 0083

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Bucuresti, Romania

Local Institution - 0051

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Cluj, Romania

Local Institution - 0020

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Badalona, Barcelona [Barcelona], Spain

Local Institution - 0029

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Santander, Cantabria, Spain

Local Institution - 0054

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Madrid, Madrid, Comunidad De, Spain

Local Institution - 0026

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Madrid, Spain

Local Institution - 0021

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Salamanca, Spain

Local Institution - 0094

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València, Spain

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