Multiple Ascending Dose of BMS-911543

Bristol-Myers Squibb (BMS)

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Cancer

Treatments: Drug: BMS-911543

Study type: Interventional

Funder types: Industry

Identifiers

NCT01236352

CA215-001

Details and patient eligibility

About

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.

Enrollment: 98 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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98 participants in 12 patient groups

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

Experimental group

Description:

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

Treatment:

Drug: BMS-911543

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

Experimental group

Description:

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

Treatment:

Drug: BMS-911543

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

Experimental group

Description:

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

Treatment:

Drug: BMS-911543

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

Experimental group

Description:

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

Treatment:

Drug: BMS-911543

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

Experimental group

Description:

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

Treatment:

Drug: BMS-911543

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

Experimental group

Description:

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

Treatment:

Drug: BMS-911543

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

Experimental group

Description:

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

Treatment:

Drug: BMS-911543

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

Experimental group

Description:

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

Treatment:

Drug: BMS-911543

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

Experimental group

Description:

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

Treatment:

Drug: BMS-911543

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

Experimental group

Description:

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

Treatment:

Drug: BMS-911543

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

Experimental group

Description:

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

Treatment:

Drug: BMS-911543

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

Experimental group

Description:

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

Treatment:

Drug: BMS-911543