Phase I/II Study Of UCN-01 In Combination With Fludarabine In Patients With Relapsed Or Refractory Chronic Lymphocytic Leukemia Or Small Lymphocytic Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 试验地点
- 6
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.
PURPOSE: Phase I/II trial to study the effectiveness of combining UCN-01 with fludarabine in treating patients who have relapsed or refractory chronic lymphocytic leukemia or lymphocytic lymphoma.
详细描述
OBJECTIVES:
- Determine the overall response rate in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma treated with UCN-01 and fludarabine.
- Assess the molecular changes in CLL cells in peripheral blood in patients treated with this regimen.
- Determine the progression-free and overall survival of patients treated with this regimen.
- Determine the toxicity of this regimen in these patients.
OUTLINE: This is a multicenter, dose-escalation study of UCN-01.
Patients receive UCN-01 IV over 3 hours on day 1 and fludarabine IV over 30-60 minutes on days 1-5. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of UCN-01 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 18-46 additional patients receive UCN-01 and fludarabine as above at the recommended phase II dose.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
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
- •DISEASE CHARACTERISTICS:
- •Histologically or cytologically confirmed chronic lymphocytic leukemia (CLL) or B-cell small lymphocytic lymphoma (SLL)
- •CLL is defined as:
- •Persistent lymphocytosis greater than 5,000/mm^3
- •CD19/CD5/CD23 positive
- •Kappa or lambda light chain restriction
- •Refractory to or disease progression after 1 or 2 prior treatment regimens
- •Retreatment with oral chlorambucil is allowed and considered a second regimen
- •At least one of the chlorambucil treatments must be for 3 months or longer
- •At least 4 courses of cyclophosphamide, vincristine, and prednisone with or without doxorubicin allowed
- •Patients may have received prior fludarabine as first- or second-line therapy if there is evidence of at least partial response and time to progression after initial fludarabine therapy was at least 12 months
- •No CNS involvement by lymphoma
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status
- •ECOG 0-2 OR
- •Karnofsky 60-100%
- •Life expectancy
- •More than 3 months
- •Hematopoietic
- •See Disease Characteristics
- •Absolute neutrophil count at least 1,000/mm^3
- •Platelet count at least 100,000/mm^3
- •No autoimmune hemolytic anemia or thrombocytopenia secondary to CLL or SLL requiring ongoing therapy with prednisone or other immunosuppressive agents
- •Bilirubin normal
- •AST and ALT no greater than 2.5 times upper limit of normal
- •Creatinine normal OR
- •Creatinine clearance at least 60 mL/min
- •Cardiovascular
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •DLCO greater than 60% predicted
- •FEV_1 greater than 70% predicted
- •No significant underlying pulmonary disease
- •No other malignancy within the past 5 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix
- •No insulin-dependent diabetes mellitus
- •No other uncontrolled concurrent illness
- •No ongoing or active infection
- •No pre-existing peripheral neuropathy grade 2 or greater
- •No psychiatric illness or social situation that would preclude study compliance
- •No prior allergic reactions to compounds of similar chemical or biological composition to UCN-01 or other agents in this study
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
- •Not specified
- •Chemotherapy
- •See Disease Characteristics
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排除标准
- 未提供