Expired Study
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Los Angeles, California 90095


Purpose:

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.


Study summary:

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.


Criteria:

INCLUSION CRITERIA: - Diagnosis of Philadelphia chromosome positive, chronic phase chronic myelogenous leukemia (CML) meeting all of the following criteria*: - Less than 15% blasts in peripheral blood and bone marrow - Less than 20% basophils in peripheral blood - Less than 30% blasts and promyelocytes in peripheral blood and bone marrow - Platelet count at least 100,000/mm^3 NOTE: *Patients who previously met the criteria for accelerated phase or blast phase CML, responded to treatment, and currently meet the criteria for chronic phase CML are eligible - Primary or acquired hematologic resistance to imatinib mesylate OR intolerance to imatinib mesylate defined as follows: - Primary hematologic resistance is defined as failure to reach complete hematologic response (CHR) with a dose of 400 mg/day continued for at least 3 months - Patients with hematological progression (i.e., WBC at least 10,000/mm^3 and rising consistently on at least 2 consecutive measurements obtained at least 14 days apart) while receiving imatinib mesylate of 400 mg/day are eligible if they have received less than 3 months of therapy - Acquired hematologic resistance is defined as achieving a CHR, but subsequently developing a rising WBC to at least 10,000/mm^3 - WBC must be at least 10,000/mm^3 and rising on at least 2 measurements obtained at least 14 days apart with at least 1 of these measurements greater than 15,000/mm^3 - Intolerance is defined as having discontinued imatinib mesylate due to nonhematologic toxicity of any grade - CD4^+ T-cell count at least 350/mm^3 - 18 and over - ECOG 0-1 - Life expectancy, At least 6 months. - Hepatic - Bilirubin no greater than 1.5 mg/dL - ALT and AST no greater than 2.0 times upper limit of normal (ULN) - Renal - Creatinine no greater than 1.5 times ULN - Potassium normal* - Magnesium normal* - Serum calcium or ionized calcium at least lower limit of normal NOTE: *Patients with low levels may be repleted to be eligible - Negative pregnancy test - Fertile patients must use effective contraception for 1 month before, during, and 1 month after study participation - More than 14 days since prior interferon - More than 14 days since prior cytarabine - More than 3 days since prior hydroxyurea - More than 28 days since other prior investigational or antineoplastic agents - More than 7 days since prior imatinib mesylate - At least 5 days or 5 half-lives since prior medications that inhibit platelet function, including the following: - Aspirin - Dipyridamole - Epoprostenol - Eptifibatide - Clopidogrel - Cilostazol - Abciximab - Ticlopidine - At least 5 days or 5 half-lives since prior anticoagulants such as warfarin or heparin/low molecular weight heparin (e.g., danaparoid, dalteparin, tinzaparin, enoxaparin) - At least 5 days or 5 half-lives since prior drugs accepted to have a risk of causing torsades de pointes, including the following: - Class IA antiarrhythmic agents (e.g., quinidine, procainamide, or disopyramide) - Class III antiarrhythmic agents (e.g., amiodarone, sotalol, ibutilide, or dofetilide) - Macrolide antibiotics (e.g., erythromycin or clarithromycin) - Antipsychotics (e.g., chlorpromazine, haloperidol, thioridazine, or pimozide) - Tricyclic antidepressants - Cisapride - Bepridil - Inapsine - Methadone - Arsenic - Concurrent anagrelide for thrombocytosis due to CML allowed 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


NCT ID:

NCT00064233


Primary Contact:

Principal Investigator
Charles Sawyers, MD
Jonsson Comprehensive Cancer Center


Backup Contact:

N/A


Location Contact:

Los Angeles, California 90095
United States



There is no listed contact information for this specific location.

Site Status: N/A


Data Source: ClinicalTrials.gov

Date Processed: December 16, 2017

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