Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04817007




Registration number
NCT04817007
Ethics application status
Date submitted
18/03/2021
Date registered
25/03/2021
Date last updated
10/05/2024

Titles & IDs
Public title
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)
Scientific 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
Secondary ID [1] 0 0
2020-002071-35
Secondary ID [2] 0 0
CA011-023
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelofibrosis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - BMS-986158
Treatment: Drugs - Ruxolitinib
Treatment: Drugs - Fedratinib

Experimental: Part 1A: BMS-986158 + Ruxolitinib -

Experimental: Part 1B: BMS-986158 + Fedratinib -

Experimental: Part 2A1: BMS-986158 + Ruxolitinib -

Experimental: Part 2B1: BMS-986158 + Fedratinib -

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

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

Experimental: Part 2A3: BMS-986158 + Ruxolitinib -


Treatment: Drugs: BMS-986158
Specified dose on specified days

Treatment: Drugs: Ruxolitinib
Specified dose on specified days

Treatment: Drugs: Fedratinib
Specified dose on specified days
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of adverse events (AEs)
Timepoint [1] 0 0
Up to 52 months
Primary outcome [2] 0 0
Incidence of serious adverse events (SAEs)
Timepoint [2] 0 0
Up to 52 months
Primary outcome [3] 0 0
Incidence of AEs meeting protocol-defined dose-limiting toxicity (DLT) criteria
Timepoint [3] 0 0
Up to 26 months
Primary outcome [4] 0 0
Incidence of AEs leading to discontinuation
Timepoint [4] 0 0
Up to 52 months
Primary outcome [5] 0 0
Incidence of death
Timepoint [5] 0 0
Up to 52 months
Secondary outcome [1] 0 0
Spleen volume reduction (SVR) at end of Cycle 6 assessed by Blinded Independent Central Review (BICR)
Timepoint [1] 0 0
Up to 175 days
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
Up to 175 days
Secondary outcome [3] 0 0
SVR at end of Cycle 3 and 6 assessed by BICR
Timepoint [3] 0 0
Up to 175 days
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
Up to 175 days
Secondary outcome [5] 0 0
Symptom response rate (SRR) based on total symptom score (TSS) measured by Myelofibrosis Symptom Assessment Form (MFSAF)
Timepoint [5] 0 0
Up to 175 days
Secondary outcome [6] 0 0
Additional measures based on TSS measured by MFSAF
Timepoint [6] 0 0
Up to 175 days
Secondary outcome [7] 0 0
For transfusion independent (TI), proportion of participants having = 2.0 g/dL hemoglobin (Hgb) increase over baseline
Timepoint [7] 0 0
Up to 24 months
Secondary outcome [8] 0 0
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
Timepoint [8] 0 0
Up to 24 months
Secondary outcome [9] 0 0
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
Timepoint [9] 0 0
Up to 24 months
Secondary outcome [10] 0 0
For transfusion dependent (TD), proportion of participants becoming Tl as measured by the absence of hydroxyurea over any consecutive 12-week period
Timepoint [10] 0 0
Up to 24 months
Secondary outcome [11] 0 0
Summary of plasma concentrations pharmacokinetics (PK) parameters: maximum observed concentration (Cmax)
Timepoint [11] 0 0
Up to 56 days
Secondary outcome [12] 0 0
Summary of plasma concentrations PK parameters: time of maximum observed concentration (Tmax)
Timepoint [12] 0 0
Up to 56 days
Secondary outcome [13] 0 0
Summary of plasma concentrations PK parameters: area under the concentration-time curve from time zero to the time of the last quantifiable concentration ((AUC (0-T))
Timepoint [13] 0 0
Up to 56 days
Secondary outcome [14] 0 0
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
Timepoint [14] 0 0
6 month and 12 month
Secondary outcome [15] 0 0
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
Timepoint [15] 0 0
6 month and 12 month

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/03/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/05/2026
Actual
Sample size
Target
216
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Local Institution - 0036 - Blacktown
Recruitment hospital [2] 0 0
Local Institution - 0032 - Wollongong
Recruitment hospital [3] 0 0
Local Institution - 0007 - East Melbourne
Recruitment hospital [4] 0 0
Local Institution - 0006 - Heidelberg
Recruitment hospital [5] 0 0
Local Institution - 0041 - Nedlands
Recruitment hospital [6] 0 0
Local Institution - 0015 - West Perth
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2500 - Wollongong
Recruitment postcode(s) [3] 0 0
3002 - East Melbourne
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment postcode(s) [6] 0 0
6005 - West Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Louisiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
New Jersey
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
France
State/province [9] 0 0
Brest
Country [10] 0 0
France
State/province [10] 0 0
Marseille
Country [11] 0 0
France
State/province [11] 0 0
Nice
Country [12] 0 0
France
State/province [12] 0 0
Paris
Country [13] 0 0
France
State/province [13] 0 0
Villejuif
Country [14] 0 0
Germany
State/province [14] 0 0
Nordrhein-Westfalen
Country [15] 0 0
Germany
State/province [15] 0 0
Sachsen-Anhalt
Country [16] 0 0
Germany
State/province [16] 0 0
Sachsen
Country [17] 0 0
Germany
State/province [17] 0 0
Schleswig-Holstein
Country [18] 0 0
Germany
State/province [18] 0 0
Erding
Country [19] 0 0
Greece
State/province [19] 0 0
Attikí
Country [20] 0 0
Greece
State/province [20] 0 0
Thessaloníki
Country [21] 0 0
Hungary
State/province [21] 0 0
Csongrád
Country [22] 0 0
Hungary
State/province [22] 0 0
Szabolcs-Szatmár-Bereg
Country [23] 0 0
Hungary
State/province [23] 0 0
Budapest
Country [24] 0 0
Hungary
State/province [24] 0 0
Debrecen
Country [25] 0 0
Israel
State/province [25] 0 0
HaDarom
Country [26] 0 0
Israel
State/province [26] 0 0
Jerusalem
Country [27] 0 0
Israel
State/province [27] 0 0
Petah-Tikva
Country [28] 0 0
Israel
State/province [28] 0 0
Ramat Gan
Country [29] 0 0
Israel
State/province [29] 0 0
Tel Aviv
Country [30] 0 0
Italy
State/province [30] 0 0
Bologna
Country [31] 0 0
Italy
State/province [31] 0 0
Brescia
Country [32] 0 0
Italy
State/province [32] 0 0
Firenze
Country [33] 0 0
Italy
State/province [33] 0 0
Verona
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Kyonggi-do
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Seoul-teukbyeolsi [Seoul]
Country [36] 0 0
Poland
State/province [36] 0 0
Pomorskie
Country [37] 0 0
Poland
State/province [37] 0 0
Gdansk
Country [38] 0 0
Romania
State/province [38] 0 0
Cluj
Country [39] 0 0
Romania
State/province [39] 0 0
Bucuresti
Country [40] 0 0
Spain
State/province [40] 0 0
Barcelona [Barcelona]
Country [41] 0 0
Spain
State/province [41] 0 0
Madrid, Comunidad De
Country [42] 0 0
Spain
State/province [42] 0 0
Madrid
Country [43] 0 0
Spain
State/province [43] 0 0
Salamanca
Country [44] 0 0
Spain
State/province [44] 0 0
Santander
Country [45] 0 0
Spain
State/province [45] 0 0
València

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04817007
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04817007