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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01236352




Registration number
NCT01236352
Ethics application status
Date submitted
5/11/2010
Date registered
7/11/2010
Date last updated
31/07/2019

Titles & IDs
Public title
Multiple Ascending Dose of BMS-911543
Scientific title
A Phase 1/2 Multiple Ascending Dose Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of BMS-911543 in Subjects With Myelofibrosis
Secondary ID [1] 0 0
CA215-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: Phase 1 (Cohort 1): BMS-911543 (5 mg) - BMS-911543 5 mg capsule by mouth twice daily for 12 months or greater depending on response

Experimental: Phase 1 (Cohort 2): BMS-911543 (10 mg) - BMS-911543 10 mg capsule by mouth twice daily for 12 months or greater depending on response

Experimental: Phase 1 (Cohort 3): BMS-911543 (20 mg) - BMS-911543 20 mg capsule by mouth twice daily for 12 months or greater depending on response

Experimental: Phase 1 (Cohort 4): BMS-911543 (40 mg) - BMS-911543 40 mg capsule by mouth twice daily for 12 months or greater depending on response

Experimental: Phase 1 (Cohort 5): BMS-911543 (80 mg) - BMS-911543 80 mg capsule by mouth twice daily for 12 months or greater depending on response

Experimental: Phase 1 (Cohort 6): BMS-911543 (120 mg) - BMS-911543 120 mg capsule by mouth twice daily for 12 months or greater depending on response

Experimental: Phase 1 (Cohort 7): BMS-911543 (160 mg) - BMS-911543 160 mg capsule by mouth twice daily for 12 months or greater depending on response

Experimental: Phase 1 (Cohort 8): BMS-911543 (200 mg) - BMS-911543 200 mg capsule by mouth twice daily for 12 months or greater depending on response

Experimental: Phase 1 (Cohort 9): BMS-911543 (240 mg) - BMS-911543 240 mg capsule by mouth twice daily for 12 months or greater depending on response

Experimental: Phase 1 (Cohort 10): BMS-911543 (320 mg) - BMS-911543 320 mg capsule by mouth twice daily for 12 months or greater depending on response

Experimental: Phase 2 (Cohort 11): BMS-911543 (120 mg) - BMS-911543 120 mg capsule by mouth twice daily for 12 months or greater depending on response

Experimental: Phase 2 (Cohort 12): BMS-911543 (200 mg) - BMS-911543 200 mg capsule by mouth twice daily for 12 months or greater depending on response
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Adverse Events
Timepoint [1] 0 0
From the date of participant's written consent until 30 days post discontinuation of dosing or participation in the study if the last scheduled visit occured at a later time, assessed up to 4.5 years
Primary outcome [2] 0 0
Number of Participants With Best Overall Response
Timepoint [2] 0 0
Day 1, at each returning on-treatment visit and the first post-treatment visit
Secondary outcome [1] 0 0
Changes in (Janus Kinase) JAK/Signal Transducers and Activators of Transcription (STATs) Pathway Activities, Circulating CD34+ Cells and Plasma Cytokine Levels
Timepoint [1] 0 0
Up to 6 months
Secondary outcome [2] 0 0
Maximum Observed Plasma Concentration (Cmax) of BMS-911543 and it's Metabolite BMS-926796 (Met4)
Timepoint [2] 0 0
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Secondary outcome [3] 0 0
Trough Observed (Pre-dose) Plasma Concentration (Cmin) of BMS-911543 and it's Metabolite Met4
Timepoint [3] 0 0
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Secondary outcome [4] 0 0
Time of Maximum Observed Plasma Concentration (Tmax) of BMS-911543 and it's Metabolite Met4
Timepoint [4] 0 0
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Secondary outcome [5] 0 0
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time (for Single Dose Period Only) (AUC(INF)) of BMS-911543 and it's Metabolite Met4
Timepoint [5] 0 0
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Secondary outcome [6] 0 0
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Plasma Concentration (for Single Dose Period Only) (AUC(0-T)) of BMS-911543 and it's Metabolite Met4
Timepoint [6] 0 0
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Secondary outcome [7] 0 0
Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) of BMS-911543 and it's Metabolite Met4
Timepoint [7] 0 0
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Secondary outcome [8] 0 0
The Terminal-phase Elimination Half-life in Plasma (T-HALF) of BMS-911543 and it's Metabolite Met4
Timepoint [8] 0 0
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Secondary outcome [9] 0 0
Apparent Total Clearance (for Parent Compound Only) (CLT/F) of BMS-911543 and it's Metabolite Met4
Timepoint [9] 0 0
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Secondary outcome [10] 0 0
Apparent Volume of Distribution After First Dosing Based on the Terminal Phase (for Parent Compound Only) (Vz/F) of BMS-911543 and it's Metabolite Met4
Timepoint [10] 0 0
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Secondary outcome [11] 0 0
Accumulation Index (AI): Ratio of AUC(TAU) on Day 15 to AUC(TAU) After the First Dose of BMS-911543 and it's Metabolite Met4
Timepoint [11] 0 0
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Secondary outcome [12] 0 0
Ratio of BMS-926796 AUC(INF) to BMS-911543 AUC(INF) After 1st Dose and BMS-926796 AUC(TAU) to BMS-911543 AUC(TAU) on Day 15 (AUC Ratio)
Timepoint [12] 0 0
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study

Eligibility
Key inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.



* Men and Women at least 18 years old
* A diagnosis of symptomatic, primary or secondary Myelofibrosis (MF) [World Health Organization (WHO) 2008 criteria] with intermediate-1, intermediate-2 or high risk disease as assessed using the Dynamic International Prognostic Scoring System international prognostic scoring system
* Last therapeutic or diagnostic treatment at least 28 days prior
* Any toxicity from prior therapies must have resolved to Grade =1
* Adequate Liver and Kidney Function
* Serum amylase and lipase within normal institutional range
* Platelet count =50,000 cell mm³
* Absolute neutrophil count (ANC) =1,000 cells/mm3
* Hemoglobin =8.0 g/dL
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Primary central nervous system tumors
* Subjects with currently active malignancy (other than MF) or with a prior history of malignancy with the exception of: (i) adequately treated basal cell carcinoma of the skin, (ii) curatively treated in situ carcinoma of the cervix, (iii) other malignancy that has undergone potentially curative therapy with no evidence of disease recurrence =3 years
* Any condition requiring chronic use of moderate/high dose steroids except inhalation or oral steroids for mild pulmonary disease
* Splenic irradiation =3 months prior to treatment with study drug
* Positive blood screen for hepatitis C antibody, hepatitis B surface antigen or Human Immunodeficiency Virus-1 (HIV-1), or HIV-2 antibodies
* Abnormalities in serum electrolytes
* Significant cardiovascular disease
* Current or recent gastrointestinal disease
* Previous history of pancreatitis and/or significant risk factors for pancreatitis as judged by the treating physician
* Evidence of uncontrolled active infection or active graft vs. host disease
* Inability to tolerate oral medication

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/04/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/11/2015
Sample size
Target
Accrual to date
Final
98
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Local Institution - East Melbourne
Recruitment hospital [2] 0 0
Local Institution - Melbourne
Recruitment postcode(s) [1] 0 0
3002 - East Melbourne
Recruitment postcode(s) [2] 0 0
3050 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Minnesota
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas

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 first in human study is to determine if BMS-911543 is safe and tolerable in subjects with symptomatic intermediate-1, intermediate-2 or high risk myelofibrosis to permit clinical testing at the Maximum Tolerated Dose or at a Clinically Active Dose, and to determine if BMS-911543 will demonstrate efficacy in symptomatic myelofibrosis.
Trial website
https://clinicaltrials.gov/study/NCT01236352
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/study/NCT01236352