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Phase I Study of BMS-354825 in Patients With Chronic Phase Chronic Myelogenous Leukemia Who Have Hematologic Resistance to Imatinib Mesylate
Alternate Title Basic Trial Information Objectives Entry Criteria Expected Enrollment Outline Published Results Trial Contact Information Registry Information
Alternate Title
BMS-354825 in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia That Is Resistant to Imatinib Mesylate
Basic Trial Information
| Phase | Type | Status | Age | Protocol IDs |
|---|
| Phase I | Treatment | Closed | 18 and over | UCLA-0303035 BMS-CA180002, NCT00064233 |
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.
Entry Criteria Disease Characteristics:
Prior/Concurrent Therapy:
Biologic therapy - More than 14 days since prior interferon
Chemotherapy - More than 14 days since prior cytarabine
- More than 3 days since prior hydroxyurea
Endocrine therapy Radiotherapy Surgery Other - See Disease Characteristics
- 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
- No concurrent drugs accepted to have a risk of causing torsades de pointes
- No other concurrent treatment for CML
- No concurrent dolasetron or droperidol
- No concurrent anticoagulants
- No concurrent medications that inhibit platelet function
- Concurrent anagrelide for thrombocytosis due to CML allowed
Patient Characteristics:
Age Performance status Life expectancy Hematopoietic - See Disease Characteristics
- No significant bleeding disorder unrelated to CML
- No acquired bleeding disorder within the past year (e.g., acquired antifactor VIII antibodies)
- No congenital bleeding disorders (e.g., von Willebrand disease)
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] Cardiovascular - No uncontrolled or significant cardiovascular disease
- No uncontrolled angina within the past 6 months
- No congestive heart failure within the past 6 months
- No myocardial infarction within the past 12 months
- No history of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
- No history of second or third degree heart block (may be eligible if patient has a pacemaker)
- No diagnosed or suspected congenital long QT syndrome
- No prolonged QTc interval on pre-entry EKG (i.e., greater than 450 msec)
- No heart rate less than 50/minute on pre-entry EKG
- No uncontrolled hypertension
- No vasculitis
Other - Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception for 1 month before, during, and 1 month after study participation
- No gastrointestinal tract bleeding within the past 6 months
- No connective tissue disorders
- No other serious uncontrolled medical disorder or active infection that would impair the ability to receive study therapy
- No dementia or altered mental status that would preclude giving informed consent
- No evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, EKG, or clinical laboratory determinations unrelated to CML
- No prisoners or patients who are compulsorily detained (e.g., involuntary incarceration for treatment of either a psychiatric or physical [e.g., infectious disease] illness)
Expected Enrollment 50Approximately 50 patients (30 for phase I and 20 for phase II) will be accrued for this study within 12-18 months. 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. Published ResultsCortes J, Sawyers CL, Kantarjian HM, et al.: Long-term efficacy of dasatinib in chronic-phase CML: results from the phase I trial (CA180002). [Abstract] Blood 110 (11): A-1026, 2007. Talpaz M, Shah NP, Kantarjian H, et al.: Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med 354 (24): 2531-41, 2006.[PUBMED Abstract] Talpaz M, Kantarjian HM, Paquette R, et al.: A phase I study of BMS-354825 in patients with imatinib-resistant and intolerant chronic phase chronic myeloid leukemia (CML): results from CA180002. [Abstract] J Clin Oncol 23 (Suppl 16): A-6519, 564s, 2005.
Trial Contact Information
Trial Lead Organizations Jonsson Comprehensive Cancer Center at UCLA  |  |  | | Charles Sawyers, MD, Principal investigator |  | | Ph: 310-206-5585; 888-798-0719 |
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| Registry Information |  | | Official Title | | A Phase I Dose-Escalation Study To Determine The Safety, Pharmacokinetics, And Pharmacodynamics Of BMS-354825 In The Treatment Of Patients With Chronic Phase Chronic Myelogenous Leukemia Who Have Hematologic Resistance To Imatinib Mesylate (GleevecTM |  | | Trial Start Date | | 2003-11-11 |  | | Registered in ClinicalTrials.gov | | NCT00064233 |  | | Date Submitted to PDQ | | 2003-05-28 |  | | Information Last Verified | | 2006-04-11 |  | | NCI Grant/Contract Number | | CA16042 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. Back to Top |
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