Multiple Ascending Dose of BMS-911543

NCT01236352 | Terminated Phase 1 Results

• 1 other identifier: CA215-001
• Study Type: interventional
• Target: 98
• Locations: 2 countries
• Sites: 5

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.

Conditions

Cancer

Keywords

Advanced Cancer, Various, NOS

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adverse Events

  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

  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 Outcomes (12)

• Changes in (Janus Kinase) JAK/Signal Transducers and Activators of Transcription (STATs) Pathway Activities, Circulating CD34+ Cells and Plasma Cytokine Levels

  Up to 6 months

• Maximum Observed Plasma Concentration (Cmax) of BMS-911543 and it's Metabolite BMS-926796 (Met4)

  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

  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

  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

  Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study

Study Arms (12)

Phase 1 (Cohort 1): BMS-911543 (5 mg)

EXPERIMENTAL

BMS-911543 5 mg capsule by mouth twice daily for 12 months or greater depending on response

Drug: BMS-911543

Phase 1 (Cohort 2): BMS-911543 (10 mg)

EXPERIMENTAL

BMS-911543 10 mg capsule by mouth twice daily for 12 months or greater depending on response

Drug: BMS-911543

Phase 1 (Cohort 3): BMS-911543 (20 mg)

EXPERIMENTAL

BMS-911543 20 mg capsule by mouth twice daily for 12 months or greater depending on response

Drug: BMS-911543

Phase 1 (Cohort 4): BMS-911543 (40 mg)

EXPERIMENTAL

BMS-911543 40 mg capsule by mouth twice daily for 12 months or greater depending on response

Drug: BMS-911543

Phase 1 (Cohort 5): BMS-911543 (80 mg)

EXPERIMENTAL

BMS-911543 80 mg capsule by mouth twice daily for 12 months or greater depending on response

Drug: BMS-911543

Phase 1 (Cohort 6): BMS-911543 (120 mg)

EXPERIMENTAL

BMS-911543 120 mg capsule by mouth twice daily for 12 months or greater depending on response

Drug: BMS-911543

Phase 1 (Cohort 7): BMS-911543 (160 mg)

EXPERIMENTAL

BMS-911543 160 mg capsule by mouth twice daily for 12 months or greater depending on response

Drug: BMS-911543

Phase 1 (Cohort 8): BMS-911543 (200 mg)

EXPERIMENTAL

BMS-911543 200 mg capsule by mouth twice daily for 12 months or greater depending on response

Drug: BMS-911543

Phase 1 (Cohort 9): BMS-911543 (240 mg)

EXPERIMENTAL

BMS-911543 240 mg capsule by mouth twice daily for 12 months or greater depending on response

Drug: BMS-911543

Phase 1 (Cohort 10): BMS-911543 (320 mg)

EXPERIMENTAL

BMS-911543 320 mg capsule by mouth twice daily for 12 months or greater depending on response

Drug: BMS-911543

Phase 2 (Cohort 11): BMS-911543 (120 mg)

EXPERIMENTAL

BMS-911543 120 mg capsule by mouth twice daily for 12 months or greater depending on response

Drug: BMS-911543

Phase 2 (Cohort 12): BMS-911543 (200 mg)

EXPERIMENTAL

BMS-911543 200 mg capsule by mouth twice daily for 12 months or greater depending on response

Drug: BMS-911543

Interventions

BMS-911543 DRUG

Also known as: JAK2 Inhibitor

Phase 1 (Cohort 1): BMS-911543 (5 mg); Phase 1 (Cohort 10): BMS-911543 (320 mg); Phase 1 (Cohort 2): BMS-911543 (10 mg); Phase 1 (Cohort 3): BMS-911543 (20 mg); Phase 1 (Cohort 4): BMS-911543 (40 mg); Phase 1 (Cohort 5): BMS-911543 (80 mg); Phase 1 (Cohort 6): BMS-911543 (120 mg); Phase 1 (Cohort 7): BMS-911543 (160 mg); Phase 1 (Cohort 8): BMS-911543 (200 mg); Phase 1 (Cohort 9): BMS-911543 (240 mg); Phase 2 (Cohort 11): BMS-911543 (120 mg); Phase 2 (Cohort 12): BMS-911543 (200 mg)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (5)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

The Mount Sinai School Of Medicine

New York, New York, 10029, United States

Location

The University Of Texas Md Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Local Institution

East Melbourne, Victoria, 3002, Australia

Location

Local Institution

Melbourne, Victoria, 3050, Australia

Location

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Neoplasms; Pyloric Stenosis, Hypertrophic

Interventions

N,N-dicyclopropyl-4-((1,5-dimethyl-1H-pyrazol-3-yl)amino)-6-ethyl-1-methyl-1,6-dihydroimidazo(4,5-d)pyrrolo(2,3b)pyridine-7-carboxamide

Condition Hierarchy (Ancestors)

Pyloric Stenosis; Gastric Outlet Obstruction; Stomach Diseases; Gastrointestinal Diseases; Digestive System Diseases

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2010
• First Posted: November 8, 2010
• Study Start: April 7, 2011
• Primary Completion: November 19, 2015
• Study Completion: November 19, 2015
• Last Updated: July 31, 2019
• Results First Posted: May 21, 2019

Record last verified: 2019-07

Locations

AU (2); US (3)