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BMS-354825 in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia That Is Resistant to Imatinib Mesylate

Phase 1
Completed
Conditions
Leukemia
Registration Number
NCT00064233
Lead Sponsor
Jonsson Comprehensive Cancer Center
Brief Summary

RATIONALE: BMS-354825 may stop the growth of cancer cells by stopping the enzymes necessary for cancer cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of BMS-354825 in treating patients with chronic phase chronic myelogenous leukemia that is resistant to imatinib mesylate.

Detailed Description

OBJECTIVES:

* Determine the maximum tolerated dose, maximum administered dose, dose-limiting toxicity, and a recommended phase II dose of BMS-354825 in patients with chronic phase chronic myelogenous leukemia who have hematologic resistance to imatinib mesylate.

* Determine the safety and tolerability of this drug in these patients.

* Determine the plasma pharmacokinetics of this drug in these patients.

* Determine, preliminarily, the efficacy of this drug, in terms of hematologic, cytogenetic, and molecular responses in these patients.

OUTLINE: This is an open-label, dose-escalation, multicenter study.

Patients receive oral BMS-354825 once daily on days 1-5. Courses repeat every 7 days for at least 3 months in the absence of disease progression or unacceptable toxicity. Patients may receive further treatment in the absence of disease progression.

Cohorts of 3-6 patients receive escalating doses of BMS-354825 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Once the MTD is determined, 20 additional patients receive treatment as in phase I at the MTD of BMS-354825.

Patients are followed for at least 30 days.

PROJECTED ACCRUAL: Approximately 50 patients (30 for phase I and 20 for phase II) will be accrued for this study within 12-18 months.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
42
Inclusion Criteria

Not provided

Exclusion Criteria
  • extramedullary involvement (other than liver or spleen)
  • significant bleeding disorder unrelated to CML
  • acquired bleeding disorder within the past year (e.g., acquired antifactor VIII antibodies)
  • congenital bleeding disorders (e.g., von Willebrand disease)
  • uncontrolled or significant cardiovascular disease
  • uncontrolled angina within the past 6 months
  • congestive heart failure within the past 6 months
  • myocardial infarction within the past 12 months
  • history of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
  • history of second or third degree heart block (may be eligible if patient has a pacemaker)
  • diagnosed or suspected congenital long QT syndrome
  • prolonged QTc interval on pre-entry EKG (i.e., greater than 450 msec)
  • heart rate less than 50/minute on pre-entry EKG
  • uncontrolled hypertension
  • vasculitis
  • pregnant or nursing
  • gastrointestinal tract bleeding within the past 6 months
  • connective tissue disorders
  • other serious uncontrolled medical disorder or active infection that would impair the ability to receive study therapy
  • dementia or altered mental status that would preclude giving informed consent
  • evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, EKG, or clinical laboratory determinations unrelated to CML
  • prisoners or patients who are compulsorily detained (e.g., involuntary incarceration for treatment of either a psychiatric or physical [e.g., infectious disease] illness)
  • concurrent drugs accepted to have a risk of causing torsades de pointes
  • other concurrent treatment for CML
  • concurrent dolasetron or droperidol
  • concurrent anticoagulants
  • concurrent medications that inhibit platelet function

Study & Design

Study Type
INTERVENTIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Jonsson Comprehensive Cancer Center at UCLA

🇺🇸

Los Angeles, California, United States

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