NCT00064233已完成1 期
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 (Gleevec
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 1
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Life expectancy, At least 6 months.
- •Bilirubin no greater than 1.5 mg/dL
- •ALT and AST no greater than 2.0 times upper limit of normal (ULN)
- •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:
- •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
- •Methadone
- •Concurrent anagrelide for thrombocytosis due to CML allowed
排除标准
- •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
研究者
研究点 (1)
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