A Phase II Study of Compound 506U78 in Patients With Refractory T-Cell Malignancies-POG/CCG Intergroup Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 148
- 试验地点
- 1
- 主要终点
- Early marrow CR plus PR rate at day 21
研究概览
简要总结
Phase II trial to study the effectiveness of 506U78 in treating patients with recurrent or refractory hematologic cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.
详细描述
OBJECTIVES:
I. Determine the response rate to compound 506U78 (2-amino-9-b-D-arabinofuranosyl-6-methoxy-9H-purine) administered as a 1 hour infusion daily for 5 days in patients with recurrent T-cell malignancies.
II. Determine the toxicities of compound 506U78 in this group of patients. III. Correlate the biochemical pharmacology of compound 506U78 (e.g., ara-G nucleotides in leukemic blasts and CSF concentrations) with clinical response.
IV. Determine the impact of compound 506U78 therapy on survival and duration of response of patients with recurrent T-cell malignancies.
OUTLINE: Patients are stratified according to disease characteristics: Group 1: T-cell ALL or NHL in first relapse (greater than 25% bone marrow blasts, with or without concomitant extramedullary relapse other than CNS); Group 2: T-cell ALL or NHL in second or later relapse (greater than 25% bone marrow blasts, with or without concomitant extramedullary relapse other than CNS); Group 3: T-cell ALL or NHL with positive bone marrow and CSF (greater than 5% bone marrow blasts and CNS 2 or 3 involvement); Group 4: Extramedullary relapse and less than 25% blasts in the bone marrow (excluding isolated CNS relapse)
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Refractory or recurrent acute lymphocytic leukemia (ALL) or non-Hodgkin's lymphoma (NHL) with bone marrow involvement (T-cell disease only)
- •Isolated CNS relapse not eligible
- •Performance status - Karnofsky 50-100%
- •At least 8 weeks
- •Bilirubin no greater than 1.5 mg/dL
- •SGPT less than 5 times normal
- •Creatinine normal for age
- •Creatinine clearance or GFR at least 60 mL/min/1.73m2
- •No severe uncontrolled infection
- •No concurrent biologic therapy
- •Recovered from toxic effects
- •At least 6 weeks from administration of nitrosoureas
- •No concurrent endocrine therapy
- •At least 6 weeks from administration of craniospinal or hemi pelvic radiotherapy
排除标准
- 未提供
研究组 & 干预措施
Arm I
GROUP 1: Patients receive a 1 hour infusion of compound 506U78 daily for 5 days in the absence of neurologic toxicity. The course repeats every 21 days. If a first relapse T-cell ALL study of higher priority is not open, then the patient may continue to receive the drug every 21 days for a maximum of 2 years provided that the patient has achieved a second complete response.
GROUPS 2 and 4: Patients receive compound 506U78 every 21 days for a maximum of 2 years, in the absence of disease progression. After 3 courses a patient may be given CNS prophylaxis with triple intrathecal therapy (TIT), consisting of methotrexate, cytarabine and hydrocortisone after consultation with study coordinator. TIT should be given every 12 weeks.
GROUP 3: Patients receive compound 506U78 every 21 days for a maximum of 2 years, in the absence of disease progression. TIT will be given on day 1 of weeks 1-4, 6, 9 and every 6 weeks for 12 weeks, and then every 9 weeks thereafter. This stratum is open.
干预措施: nelarabine (Drug)
Arm I
GROUP 1: Patients receive a 1 hour infusion of compound 506U78 daily for 5 days in the absence of neurologic toxicity. The course repeats every 21 days. If a first relapse T-cell ALL study of higher priority is not open, then the patient may continue to receive the drug every 21 days for a maximum of 2 years provided that the patient has achieved a second complete response.
GROUPS 2 and 4: Patients receive compound 506U78 every 21 days for a maximum of 2 years, in the absence of disease progression. After 3 courses a patient may be given CNS prophylaxis with triple intrathecal therapy (TIT), consisting of methotrexate, cytarabine and hydrocortisone after consultation with study coordinator. TIT should be given every 12 weeks.
GROUP 3: Patients receive compound 506U78 every 21 days for a maximum of 2 years, in the absence of disease progression. TIT will be given on day 1 of weeks 1-4, 6, 9 and every 6 weeks for 12 weeks, and then every 9 weeks thereafter. This stratum is open.
干预措施: methotrexate (Drug)
Arm I
GROUP 1: Patients receive a 1 hour infusion of compound 506U78 daily for 5 days in the absence of neurologic toxicity. The course repeats every 21 days. If a first relapse T-cell ALL study of higher priority is not open, then the patient may continue to receive the drug every 21 days for a maximum of 2 years provided that the patient has achieved a second complete response.
GROUPS 2 and 4: Patients receive compound 506U78 every 21 days for a maximum of 2 years, in the absence of disease progression. After 3 courses a patient may be given CNS prophylaxis with triple intrathecal therapy (TIT), consisting of methotrexate, cytarabine and hydrocortisone after consultation with study coordinator. TIT should be given every 12 weeks.
GROUP 3: Patients receive compound 506U78 every 21 days for a maximum of 2 years, in the absence of disease progression. TIT will be given on day 1 of weeks 1-4, 6, 9 and every 6 weeks for 12 weeks, and then every 9 weeks thereafter. This stratum is open.
干预措施: cytarabine (Drug)
Arm I
GROUP 1: Patients receive a 1 hour infusion of compound 506U78 daily for 5 days in the absence of neurologic toxicity. The course repeats every 21 days. If a first relapse T-cell ALL study of higher priority is not open, then the patient may continue to receive the drug every 21 days for a maximum of 2 years provided that the patient has achieved a second complete response.
GROUPS 2 and 4: Patients receive compound 506U78 every 21 days for a maximum of 2 years, in the absence of disease progression. After 3 courses a patient may be given CNS prophylaxis with triple intrathecal therapy (TIT), consisting of methotrexate, cytarabine and hydrocortisone after consultation with study coordinator. TIT should be given every 12 weeks.
GROUP 3: Patients receive compound 506U78 every 21 days for a maximum of 2 years, in the absence of disease progression. TIT will be given on day 1 of weeks 1-4, 6, 9 and every 6 weeks for 12 weeks, and then every 9 weeks thereafter. This stratum is open.
干预措施: therapeutic hydrocortisone (Drug)
结局指标
主要结局
Early marrow CR plus PR rate at day 21
时间窗: Day 21
CR is defined by an M1 marrow which requires blast counts below 5%. PR is defined by an M2 marrow which requires blast counts below 25%.
次要结局
- Remission duration(Up to 2 years)
- 6 month cumulative event-free survival(6 months)