Phase III Study of MDR Modulation With PSC-833 (NSC #648265) Followed by Immunotherapy With rIL-2 (NSC #373364) vs. No Further Therapy in Previously Untreated Patients With AML >60 Years
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 640
- 试验地点
- 1
- 主要终点
- Overall survival
研究概览
简要总结
Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without PSC 833 followed by interleukin-2 or no further therapy in treating older patients who have acute myeloid leukemia. Some cancers become resistant to chemotherapy drugs. Combining PSC 833 with more than one chemotherapy drug may reduce resistance to the drugs and allow the cancer cells to be killed. Combining interleukin-2 with combination chemotherapy plus PSC 833 may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine whether the addition of PSC-833 to induction chemotherapy improves complete response rates and whether the addition of PSC-833 to induction and consolidation chemotherapy improves survival for patients with AML >= 60 years.
II. To determine whether the administration of low-dose, subcutaneous rIL-2 immunotherapy with intermittent high-dose boluses after chemotherapy prolongs disease-free survival.
OUTLINE: This is a partially randomized, multicenter study. Patients are stratified according to participating center and disease characteristics (de novo acute myeloid leukemia (AML) versus AML with antecedent myelodysplasia). Patients are randomized to one of two maintenance therapy arms.
Arm I: Patients receive cytarabine IV continuously over 7 days and daunorubicin IV bolus followed by etoposide IV over 2 hours on days 1-3.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Unequivocal histologic diagnosis of AML, FAB classification (M0-M7), excluding M3 (acute promyelocytic leukemia); patients with a history of antecedent myelodysplasia remain eligible for treatment on this trial
- •No prior treatment for acute leukemia or myelodysplasia with four permissible exceptions:
- •Emergency leukapheresis;
- •Emergency treatment for hyperleukocytosis with hyroxyurea;
- •Cranial RT for CNS leukostasis (one dose only);
- •Growth factor/cytokine support.
排除标准
- 未提供
研究组 & 干预措施
Arm I (cytarabine, daunorubicin, etoposide)
Patients receive cytarabine IV continuously over 7 days and daunorubicin IV bolus followed by etoposide IV over 2 hours on days 1-3.
干预措施: cytarabine (Drug)
Arm I (cytarabine, daunorubicin, etoposide)
Patients receive cytarabine IV continuously over 7 days and daunorubicin IV bolus followed by etoposide IV over 2 hours on days 1-3.
干预措施: daunorubicin hydrochloride (Drug)
Arm I (cytarabine, daunorubicin, etoposide)
Patients receive cytarabine IV continuously over 7 days and daunorubicin IV bolus followed by etoposide IV over 2 hours on days 1-3.
干预措施: etoposide (Drug)
Arm II (valspodar, daunorubicin, etoposide, cytarabine)
Patients receive treatment as in arm I with the addition of PSC 833 induction. A loading dose of PSC 833 IV is given over 2 hours, followed by a 74-hour continuous infusion of PSC 833 beginning 2 hours before daunorubicin and etoposide. Patients may receive a second induction course if residual leukemia is present in the bone marrow. Patients who experience a CR and meet certain other criteria receive postremission chemotherapy consisting of cytarabine IV continuously over 5 days plus daunorubicin IV followed by etoposide IV over 2 hours on days 1 and 2. Patients who are randomized to receive PSC 833 during induction chemotherapy receive a loading dose of PSC 833 before beginning a 48-hour continuous infusion of PSC 833 concurrently with cytarabine/daunorubicin/etoposide postremission chemotherapy.
After completing postremission chemotherapy, patients are randomized to a no further treatment group or IL-2 immunotherapy.
干预措施: cytarabine (Drug)
Arm II (valspodar, daunorubicin, etoposide, cytarabine)
Patients receive treatment as in arm I with the addition of PSC 833 induction. A loading dose of PSC 833 IV is given over 2 hours, followed by a 74-hour continuous infusion of PSC 833 beginning 2 hours before daunorubicin and etoposide. Patients may receive a second induction course if residual leukemia is present in the bone marrow. Patients who experience a CR and meet certain other criteria receive postremission chemotherapy consisting of cytarabine IV continuously over 5 days plus daunorubicin IV followed by etoposide IV over 2 hours on days 1 and 2. Patients who are randomized to receive PSC 833 during induction chemotherapy receive a loading dose of PSC 833 before beginning a 48-hour continuous infusion of PSC 833 concurrently with cytarabine/daunorubicin/etoposide postremission chemotherapy.
After completing postremission chemotherapy, patients are randomized to a no further treatment group or IL-2 immunotherapy.
干预措施: daunorubicin hydrochloride (Drug)
Arm II (valspodar, daunorubicin, etoposide, cytarabine)
Patients receive treatment as in arm I with the addition of PSC 833 induction. A loading dose of PSC 833 IV is given over 2 hours, followed by a 74-hour continuous infusion of PSC 833 beginning 2 hours before daunorubicin and etoposide. Patients may receive a second induction course if residual leukemia is present in the bone marrow. Patients who experience a CR and meet certain other criteria receive postremission chemotherapy consisting of cytarabine IV continuously over 5 days plus daunorubicin IV followed by etoposide IV over 2 hours on days 1 and 2. Patients who are randomized to receive PSC 833 during induction chemotherapy receive a loading dose of PSC 833 before beginning a 48-hour continuous infusion of PSC 833 concurrently with cytarabine/daunorubicin/etoposide postremission chemotherapy.
After completing postremission chemotherapy, patients are randomized to a no further treatment group or IL-2 immunotherapy.
干预措施: etoposide (Drug)
Arm II (valspodar, daunorubicin, etoposide, cytarabine)
Patients receive treatment as in arm I with the addition of PSC 833 induction. A loading dose of PSC 833 IV is given over 2 hours, followed by a 74-hour continuous infusion of PSC 833 beginning 2 hours before daunorubicin and etoposide. Patients may receive a second induction course if residual leukemia is present in the bone marrow. Patients who experience a CR and meet certain other criteria receive postremission chemotherapy consisting of cytarabine IV continuously over 5 days plus daunorubicin IV followed by etoposide IV over 2 hours on days 1 and 2. Patients who are randomized to receive PSC 833 during induction chemotherapy receive a loading dose of PSC 833 before beginning a 48-hour continuous infusion of PSC 833 concurrently with cytarabine/daunorubicin/etoposide postremission chemotherapy.
After completing postremission chemotherapy, patients are randomized to a no further treatment group or IL-2 immunotherapy.
干预措施: valspodar (Drug)
结局指标
主要结局
Overall survival
时间窗: Up to 10 years
Disease-free survival
时间窗: From second randomization to relapse or death, assessed up to 10 years
Analyzed by intention to treat.
次要结局
未报告次要终点