- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01236352
Multiple Ascending Dose of BMS-911543
July 29, 2019 updated by: Bristol-Myers Squibb
A Phase 1/2 Multiple Ascending Dose Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of BMS-911543 in Subjects With Myelofibrosis
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.
Study Overview
Study Type
Interventional
Enrollment (Actual)
98
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Victoria
-
East Melbourne, Victoria, Australia, 3002
- Local Institution
-
Melbourne, Victoria, Australia, 3050
- Local Institution
-
-
-
-
Minnesota
-
Rochester, Minnesota, United States, 55905
- Mayo Clinic
-
-
New York
-
New York, New York, United States, 10029
- The Mount Sinai School of Medicine
-
-
Texas
-
Houston, Texas, United States, 77030
- The University of Texas MD Anderson Cancer Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.
Inclusion Criteria:
- 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
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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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
|
Other Names:
|
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
|
Other Names:
|
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
|
Other Names:
|
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
|
Other Names:
|
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
|
Other Names:
|
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
|
Other Names:
|
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
|
Other Names:
|
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
|
Other Names:
|
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
|
Other Names:
|
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
|
Other Names:
|
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
|
Other Names:
|
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
|
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Adverse Events
Time Frame: 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
|
Safety assessments were based on a medical review of adverse event reports and the results of vital sign measurements, ECGs, physical examinations, and clinical laboratory tests and were evaluated for all treated participants using National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 (NCI CTCAE v.4.0).
|
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
|
Number of Participants With Best Overall Response
Time Frame: Day 1, at each returning on-treatment visit and the first post-treatment visit
|
Participants were clinically assessed for IWG-(International Working Group consensus criteria for treatment response in myelofibrosis with myeloid metaplasia) defined response at each returning on-treatment visit and the first post-treatment visit.
IWG-MRT criteria for best overall response are ordered high to low: CR>PR>CI>SD>PD>R where CR = Complete Remission, PR= Partial Remission, CI = Clinical Improvement, SD = Stable Disease, PD = Progressive Disease and R = Relapse.
Best overall response is the best response of the subject during the treatment period or at the first post-treatment visit.
|
Day 1, at each returning on-treatment visit and the first post-treatment visit
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in (Janus Kinase) JAK/Signal Transducers and Activators of Transcription (STATs) Pathway Activities, Circulating CD34+ Cells and Plasma Cytokine Levels
Time Frame: Up to 6 months
|
JAK/STAT pathway activity will be evaluated by: 1) pSTATs levels using immunoassay; 2) expression levels of several JAK/STATs pathway genes.
Whole blood will be collected at specific time-points.
Due to portfolio/business decisions by the sponsor, the compound is no longer being developed and the study was terminated.
Analysis was not completed because the study was terminated.
This decision was not based on any safety concerns associated with BMS-911543.
|
Up to 6 months
|
Maximum Observed Plasma Concentration (Cmax) of BMS-911543 and it's Metabolite BMS-926796 (Met4)
Time Frame: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
|
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time.
The pharmacokinetic parameters to be assessed include: Cmax Maximum observed plasma concentration
|
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
|
Trough Observed (Pre-dose) Plasma Concentration (Cmin) of BMS-911543 and it's Metabolite Met4
Time Frame: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
|
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time.
The pharmacokinetic parameters to be assessed include: Cmin (Trough observed (pre-dose) plasma concentration)
|
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
|
Time of Maximum Observed Plasma Concentration (Tmax) of BMS-911543 and it's Metabolite Met4
Time Frame: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
|
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time.
The pharmacokinetic parameters to be assessed include: Tmax = Time of maximum observed plasma concentration (Tmax) of BMS-911543 and it's metabolite Met4
|
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
|
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
Time Frame: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
|
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time.
The pharmacokinetic parameters to be assessed include: AUC(INF) = 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
|
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
|
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
Time Frame: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
|
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time.
The pharmacokinetic parameters to be assessed include: AUC (0-T) = Area under the plasma concentration-time curve from time zero to the time of last quantifiable plasma concentration (for single dose period only) of BMS-911543 and it's metabolite Met4
|
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
|
Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) of BMS-911543 and it's Metabolite Met4
Time Frame: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
|
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time.
The pharmacokinetic parameters to be assessed include: AUC (TAU) = Area under the concentration-time curve in one dosing interval of BMS-911543 and it's metabolite Met4
|
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
|
The Terminal-phase Elimination Half-life in Plasma (T-HALF) of BMS-911543 and it's Metabolite Met4
Time Frame: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
|
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time.
The pharmacokinetic parameters to be assessed include: T-HALF = The terminal-phase elimination half-life in plasma of BMS-911543 and it's metabolite Met4
|
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
|
Apparent Total Clearance (for Parent Compound Only) (CLT/F) of BMS-911543 and it's Metabolite Met4
Time Frame: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
|
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time.
The pharmacokinetic parameters to be assessed include: CLT/F = Apparent total clearance (for parent compound only) of BMS-911543 and it's metabolite Met4
|
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
|
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
Time Frame: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
|
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time.
The pharmacokinetic parameters to be assessed include: Vz/F = Apparent volume of distribution after first dosing based on the terminal phase (for parent compound only) of BMS-911543 and it's metabolite Met4
|
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
|
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
Time Frame: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
|
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time.
The pharmacokinetic parameters to be assessed include: 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
|
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
|
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)
Time Frame: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
|
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time.
The pharmacokinetic parameters to be assessed include: AUC Ratio = 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
|
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 7, 2011
Primary Completion (Actual)
November 19, 2015
Study Completion (Actual)
November 19, 2015
Study Registration Dates
First Submitted
November 5, 2010
First Submitted That Met QC Criteria
November 5, 2010
First Posted (Estimate)
November 7, 2010
Study Record Updates
Last Update Posted (Actual)
July 31, 2019
Last Update Submitted That Met QC Criteria
July 29, 2019
Last Verified
July 1, 2019
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- CA215-001
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cancer
-
University of Michigan Rogel Cancer CenterRecruitingCancer Liver | Cancer Brain | Cancer Head &Neck | Cancer PelvisUnited States
-
Cellworks Group Inc.RecruitingCancer | Relapsed Cancer | Refractory CancerUnited States
-
UNC Lineberger Comprehensive Cancer CenterHyundai Hope On WheelsRecruitingCancer | Pediatric Cancer | Survivorship | Cancer MetastaticUnited States
-
Vanderbilt-Ingram Cancer CenterNational Institutes of Health (NIH)Active, not recruitingAdvanced Cancer | Relapsed Cancer | Refractory CancerUnited States
-
MiRXES Pte LtdRecruitingBreast Cancer | Gastric Cancer | Colorectal Cancer | Pancreatic Cancer | Esophageal Cancer | Ovarian Cancer | Prostate Cancer | Thoracic Cancer | Liver CancerSingapore
-
Sidney Kimmel Cancer Center at Thomas Jefferson...CompletedStage I Breast Cancer | Stage I Uterine Corpus Cancer | Stage II Uterine Corpus Cancer | Stage III Uterine Corpus Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage... and other conditionsUnited States
-
Massachusetts General HospitalNational Comprehensive Cancer NetworkCompletedGastric Cancer | Pancreatic Cancer | Esophageal Cancer | Rectal Cancer | Colon Cancer | Hepatobiliary CancerUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)CompletedStage III Pancreatic Cancer | Stage IIA Pancreatic Cancer | Stage IIB Pancreatic Cancer | Stage IV Gastric Cancer | Stage IVA Colorectal Cancer | Stage IVA Pancreatic Cancer | Stage IVB Colorectal Cancer | Stage IVB Pancreatic Cancer | Stage IIIA Gastric Cancer | Stage IIIB Gastric Cancer | Stage IIIC Gastric... and other conditionsUnited States
-
Johns Hopkins UniversityNational Cancer Institute (NCI); National Institute on Minority Health and...Enrolling by invitationCancer | Advanced Cancer | End Stage Cancer | MalignancyUnited States
-
University of California, San FranciscoBristol-Myers Squibb; PfizerTerminatedStage IIIA Rectal Cancer | Stage IIIB Rectal Cancer | Stage IIIC Rectal Cancer | Metastatic Colorectal Adenocarcinoma | Metastatic Colon Adenocarcinoma | Metastatic Rectal Adenocarcinoma | Stage IIIA Colon Cancer | Stage IIIB Colon Cancer | Stage IIIC Colon Cancer | Stage IV Colon Cancer | Stage IV Rectal... and other conditionsUnited States
Clinical Trials on BMS-911543
-
China National Center for Cardiovascular DiseasesPeking University People's Hospital; Beijing Chao Yang Hospital; Hebei Medical...UnknownCoronary Artery EctasiaChina
-
CelgeneRecruitingProstatic NeoplasmsUnited States
-
Bristol-Myers SquibbCompletedHeart FailureUnited States
-
Bristol-Myers SquibbRecruitingProgressive Pulmonary FibrosisChina, United States, Japan, Korea, Republic of, Hungary, Canada, Argentina, Australia, Austria, Belgium, Brazil, Chile, Colombia, Czechia, Denmark, Finland, France, Germany, Greece, India, Ireland, Italy, Mexico, Netherlands, Peru, Poland, Portuga... and more
-
Bristol-Myers SquibbRecruitingIdiopathic Pulmonary FibrosisChina, Taiwan, United States, Australia, Japan, United Kingdom, Korea, Republic of, Israel, Canada, Argentina, Austria, Belgium, Brazil, Chile, Colombia, Czechia, Denmark, Finland, France, Germany, Greece, Hungary, India, Ireland, Italy, ... and more
-
Bristol-Myers SquibbCompleted
-
Bristol-Myers SquibbCompletedHeart Decompensation, AcuteUnited States
-
Bristol-Myers SquibbRecruitingLupusUnited States, Argentina, Germany, Mexico, Poland, Romania, Bulgaria, Spain
-
Bristol-Myers SquibbTerminatedVarious Advanced CancerAustralia, United States, Canada
-
Bristol-Myers SquibbCompleted