The Value of High Dose Versus Standard Dose ARA-C During Induction and of IL-2 After Intensive Consolidation/Autologous Stem Cell Transplantation in Patients (Age 15-60 Years) With Acute Myelogenous Leukemia. A Randomized Phase II Trial of the EORTC and the GIMEMA-ALWP
试验速览
- 阶段
- 3 期
- 入组人数
- 2,000
- 主要终点
- Duration of overall survival and disease-free survival after first randomization
研究概览
简要总结
RATIONALE: Giving combination chemotherapy before a peripheral blood stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood or bone marrow and stored. More chemotherapy or radiation therapy is given prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy. Interleukin-2 may stimulate the patient's white blood cells to kill cancer cells.
PURPOSE: This randomized phase III trial is studying two different regimens of combination chemotherapy, interleukin-2, and peripheral stem cell transplant and comparing them to see how well they work in treating patients with acute myeloid leukemia.
详细描述
OBJECTIVES:
- Compare the overall survival rate in patients with acute myeloid leukemia treated with high-dose versus standard-dose cytarabine during induction.
- Compare the disease-free survival rate in patients treated with or without interleukin-2 following consolidation and autologous peripheral blood stem cell or bone marrow transplantation.
- Compare the feasibility of these regimens in these patients.
OUTLINE: This is a randomized, multicenter study. Patients in the first randomization are stratified according to center, WBC (no greater than 25,000/mm^3 vs 25,000-99,000/mm^3 vs at least 100,000/mm^3), age (15 to 45 vs 46 to 60), and performance status (0-1 vs 2 vs 3). Patients in the second randomization are stratified according to center, first treatment arm (I vs II), number of induction courses to reach complete remission (CR), cytogenic/molecular genetic group at diagnosis (low vs high vs intermediate vs unknown), and autologous peripheral blood stem cell (PBSC) transplantation planned after consolidation (yes vs no).
First randomization
- Induction: Patients are randomized to 1 of 2 treatment arms:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Treatment
入排标准
- 年龄范围
- 15 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •First randomization:
- •Untreated newly diagnosed acute myeloid leukemia (AML)
- •At least 30% blasts in bone marrow
- •All cytological types of AML except acute promyelocytic leukemia (M3)
- •No blast crisis of chronic myelogenous leukemia
- •No leukemias supervening after other myeloproliferative disease
- •No leukemias supervening after overt myelodysplastic disorders (e.g., refractory anemia with excess blasts) for more than 6 months duration
- •Second randomization:
- •Must have achieved complete remission with full hematologic recovery following consolidation treatment
- •No HLA identical family donor
- •Not eligible for allograft
- •No high risk patient (under age 40) for whom an unrelated bone marrow donor has been found within 8 weeks of beginning consolidation treatment
- •PATIENT CHARACTERISTICS:
- •Performance status:
- •WHO 0-3 (first randomization)
- •WHO 0-2 (second randomization)
- •Life expectancy:
- •Not specified
- •Hematopoietic:
- •Not specified
- •Bilirubin no greater than 3 times upper limit of normal (ULN)
- •Creatinine no greater than 3 times ULN
- •Cardiovascular:
- •No severe heart failure requiring diuretics
- •Ejection fraction at least 50%
- •First randomization:
- •No other progressive malignant disease except the following:
- •Secondary acute leukemias following curatively treated Hodgkin's disease (even if treated with anthracyclines)
- •Other curatively treated malignancies
- •Secondary leukemias following other exposure to alkylating agents or radiotherapy for other reason
- •No uncontrolled infection
- •No severe concurrent neurologic or psychiatric disease
- •No psychological, familial, sociological, or geographical condition that could preclude compliance
- •Second randomization:
- •No nonmalignant systemic illness that would increase risk of participation in study
- •No uncontrolled infection
- •No other progressive malignant disease
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy:
- •Not specified
- •Chemotherapy:
- •No prior chemotherapy for AML except hydroxyurea
- •Less than 7 days of prior hydroxyurea
- •Endocrine therapy:
- •No more than 7 days of prior corticosteroid therapy for AML
- •Radiotherapy:
- •No prior radiotherapy for AML
- •Not specified
排除标准
- 未提供
结局指标
主要结局
Duration of overall survival and disease-free survival after first randomization
Duration of overall survival and disease-free survival after second randomization
次要结局
- Response after induction and consolidation
- Toxicity measured by Cancer and Leukemia Group B (CALGB) CTCAE v3.0 after induction and consolidation
- Disease-free survival after complete remission (CR)
- Disease-free interval from CR
- Time to death in CR
- Peripheral stem cell harvest after consolidation
- Rate of completion of autologous peripheral blood stem cell transplantation (auto-PBSCT) and allogeneic stem cell transplantation (allo-SCT)