Multiple Ascending Dose of BMS-911543

Phase 2TerminatedNCT01236352

Bristol-Myers Squibb98 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Cancer

Interventions

BMS-911543DRUG

Eligibility

Sex: ALL

Medical Language ↔ Plain English

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

Locations (5)

Mayo Clinic

Rochester, Minnesota, United States

The Mount Sinai School Of Medicine

New York, New York, United States

The University Of Texas Md Anderson Cancer Center

Houston, Texas, United States

Local Institution

East Melbourne, Victoria, Australia

Outcomes

Primary Outcomes

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).

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

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.

Time frame: Day 1, at each returning on-treatment visit and the first post-treatment visit

Secondary Outcomes

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

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.

Time frame: Up to 6 months

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

Data from ClinicalTrials.gov

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Local Institution

Melbourne, Victoria, Australia