Clinical trial NCT04817007: 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: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Myelofibrosis
Keywords: BMS-986158
Fedratinib
Myelofibrosis
Ruxolitinib
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2021-03-25
Enrollment: 216
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Incidence of adverse events (AEs)
timeFrame: Up to 52 months
measure: Incidence of serious adverse events (SAEs)
timeFrame: Up to 52 months
measure: Incidence of AEs meeting protocol-defined dose-limiting toxicity (DLT) criteria
timeFrame: Up to 26 months
measure: Incidence of AEs leading to discontinuation
timeFrame: Up to 52 months
measure: Incidence of death
timeFrame: Up to 52 months
Secondary outcomes:
measure: Spleen volume reduction (SVR) at end of Cycle 6 assessed by Blinded Independent Central Review (BICR)
timeFrame: Up to 175 days
measure: 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 BICR
timeFrame: Up to 175 days
measure: SVR at end of Cycle 3 and 6 assessed by BICR
timeFrame: Up to 175 days
measure: 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 BICR
timeFrame: Up to 175 days
measure: Symptom response rate (SRR) based on total symptom score (TSS) measured by Myelofibrosis Symptom Assessment Form (MFSAF)
timeFrame: Up to 175 days
measure: Additional measures based on TSS measured by MFSAF
timeFrame: Up to 175 days
Other outcomes:
Locations:
city: Newport Beach
country: United States
facility: Local Institution - 0069
state: California
city: Lake Mary
country: United States
facility: Local Institution - 0090
state: Florida
city: New Orleans
country: United States
facility: Local Institution - 0043
state: Louisiana
city: Worcester
country: United States
facility: Local Institution - 0038
state: Massachusetts
city: Ann Arbor
country: United States
facility: Local Institution - 0033
state: Michigan
city: Hackensack
country: United States
facility: Local Institution - 0045
state: New Jersey
city: Chapel Hill
country: United States
facility: Local Institution - 0076
state: North Carolina
city: Pittsburgh
country: United States
facility: Local Institution - 0042
state: Pennsylvania
city: Blacktown
country: Australia
facility: Local Institution - 0036
state: New South Wales
city: Wollongong
country: Australia
facility: Local Institution - 0032
state: New South Wales
city: East Melbourne
country: Australia
facility: Local Institution - 0007
state: Victoria
city: Heidelberg
country: Australia
facility: Local Institution - 0006
state: Victoria
city: Nedlands
country: Australia
facility: Local Institution - 0041
state: Western Australia
city: West Perth
country: Australia
facility: Local Institution - 0015
state: Western Australia
city: Brest
country: France
facility: Local Institution - 0030
city: Marseille
country: France
facility: Local Institution - 0008
city: Nice
country: France
facility: Local Institution - 0027
city: Paris
country: France
facility: Local Institution - 0011
city: Villejuif
country: France
facility: Local Institution - 0010
city: Erding
country: Germany
facility: Local Institution - 0068
state: Bayern
city: Essen
country: Germany
facility: Local Institution - 0039
state: Nordrhein-Westfalen
city: Halle
country: Germany
facility: Local Institution - 0035
state: Sachsen-Anhalt
city: Chemnitz
country: Germany
facility: Local Institution - 0040
state: Sachsen
city: Lübeck
country: Germany
facility: Local Institution - 0050
state: Schleswig-Holstein
city: Chaidari
country: Greece
facility: Local Institution - 0061
state: Attikí
city: Thessaloniki
country: Greece
facility: Local Institution - 0047
state: Thessaloníki
city: Szeged
country: Hungary
facility: Local Institution - 0073
state: Csongrád
city: Nyiregyhaza
country: Hungary
facility: Local Institution - 0072
state: Szabolcs-Szatmár-Bereg
city: Budapest
country: Hungary
facility: Local Institution - 0075
city: Debrecen
country: Hungary
facility: Local Institution - 0074
city: Be'er Sheva
country: Israel
facility: Local Institution - 0086
state: HaDarom
city: Jerusalem
country: Israel
facility: Local Institution - 0016
city: Petah-Tikva
country: Israel
facility: Local Institution - 0018
city: Ramat Gan
country: Israel
facility: Local Institution - 0017
city: Tel Aviv
country: Israel
facility: Local Institution - 0019
city: Bologna
country: Italy
facility: Local Institution - 0003
city: Brescia
country: Italy
facility: Local Institution - 0002
city: Firenze
country: Italy
facility: Local Institution - 0001
city: Verona
country: Italy
facility: Local Institution - 0012
city: Seongnam
country: Korea, Republic of
facility: Local Institution - 0049
state: Kyǒnggi-do
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0048
state: Seoul-teukbyeolsi [Seoul]
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0053
state: Seoul-teukbyeolsi [Seoul]
city: Słupsk
country: Poland
facility: Local Institution - 0077
state: Pomorskie
city: Gdańsk
country: Poland
facility: Local Institution - 0062
city: Bucuresti
country: Romania
facility: Local Institution - 0052
state: Cluj
city: Bucuresti
country: Romania
facility: Local Institution - 0083
city: Cluj
country: Romania
facility: Local Institution - 0051
city: Badalona
country: Spain
facility: Local Institution - 0020
state: Barcelona [Barcelona]
city: Santander
country: Spain
facility: Local Institution - 0029
state: Cantabria
city: Madrid
country: Spain
facility: Local Institution - 0054
state: Madrid, Comunidad De
city: Madrid
country: Spain
facility: Local Institution - 0026
city: Salamanca
country: Spain
facility: Local Institution - 0021
city: València
country: Spain
facility: Local Institution - 0094
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: