Treatment Optimization Trial in Chronic Myeloid Leukemia (CML) - Randomized Controlled Comparison of Imatinib vs. Imatinib/Interferon-alpha vs. Imatinib/Low-Dose AraC vs. Interferon-alpha Standard Therapy and Determination of the Role of Allografting in Newly Diagnosed Chronic Phase
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,551
- 试验地点
- 66
- 主要终点
- Hematologic, cytogenetic, and molecular response rates
研究概览
简要总结
RATIONALE: Giving chemotherapy before a donor bone marrow transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Also, imatinib mesylate may stop the growth of cancer cells by blocking the enzymes needed for cancer cell growth. Interferon alfa may interfere with the growth of cancer cells and slow the growth of cancer. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. It is not yet known which treatment regimen is most effective in treating chronic phase chronic myelogenous leukemia.
PURPOSE: This randomized phase III trial is studying imatinib mesylate with or without interferon alfa or cytarabine to see how well it works compared with interferon alfa followed by donor stem cell transplant in treating patients with newly diagnosed chronic phase chronic myelogenous leukemia.
详细描述
OBJECTIVES:
- Compare the hematologic, cytogenetic, and molecular response rates in patients with newly diagnosed chronic phase chronic myelogenous leukemia treated with imatinib mesylate alone or with interferon alfa or low-dose cytarabine vs interferon alfa standard therapy.
- Compare the group-dependent, progression-free and overall survival and time to progression in patients treated with these regimens.
- Compare the efficacy of allogeneic stem cell transplantation vs imatinib mesylate-based therapy in patients eligible for transplantation.
- Compare the efficacy of reduced-intensity conditioning vs standard conditioning in patients over 45 years of age.
- Determine the time to and duration of hematologic, cytogenetic, and molecular responses and correlate these factors in patients treated with these regimens.
- Compare the short- and long-term adverse effects of these regimens in these patients.
- Compare the presentation, duration, and responses to therapy of accelerated and blastic phases in patients treated with these regimens.
- Determine the survival of high-risk patients after early allografting.
- Determine the influence of pre-transplantation therapies on the outcome of allogeneic stem cell transplantation in these patients.
OUTLINE: This is a randomized, multicenter, pilot study. Patients are stratified according to participating center. Patients with low- to intermediate-risk disease are randomized to 1 of 4 treatment arms. Patients with high-risk disease are randomized to 1 of 3 treatment arms with imatinib mesylate-based regimens.
- Arm I: Patients receive oral imatinib mesylate once daily for up to 12 months in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive oral imatinib mesylate as in arm I. Patients also receive interferon alfa subcutaneously (SC) 3 times a week beginning at least 3 months after the start of imatinib mesylate.
- Arm III: Patients receive oral imatinib mesylate as in arm I. Patients also receive cytarabine SC up to twice daily for 5 days monthly beginning at least 3 months after the start of imatinib mesylate.
- Arm IV: After initial cytoreduction with hydroxyurea, patients receive interferon alfa SC daily with or without hydroxyurea. In the absence of a complete response after 3 months, patients may also receive low-dose cytarabine SC once daily. Treatment continues for up to 21 months.
Patients who fail interferon alfa therapy are crossed over to receive imatinib mesylate.
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
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Newly diagnosed chronic phase chronic myelogenous leukemia (CML)
- •bcr-abl positive
- •No blasts, promyelocytes, myelocytes, or metamyelocytes in the peripheral blood
- •Availability of a HLA-identical sibling or unrelated donor
- •PATIENT CHARACTERISTICS:
- •Performance status
- •Not specified
- •Life expectancy
- •Not specified
- •Hematopoietic
- •Not specified
- •Not specified
- •Not specified
- •Not pregnant or nursing
- •Fertile patients must use effective contraception
- •No second malignancy requiring therapy
- •No evidence of disease-related symptoms or extramedullary disease (including hepatosplenomegaly)
- •No serious diseases that would preclude study participation
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
- •No prior interferon
- •Chemotherapy
- •No prior chemotherapy other than hydroxyurea
- •Endocrine therapy
- •Not specified
- •Radiotherapy
- •No prior radiotherapy
- •Not specified
- •Prior anagrelide allowed
- •No participation in another clinical trial
排除标准
- 未提供
结局指标
主要结局
Hematologic, cytogenetic, and molecular response rates
Risk group-dependent survival
Overall survival
Progression-free survival
次要结局
- Adverse drug effects
- Quality of life
研究者
Prof. Dr. Dr. h.c. R. Hehlmann
Investigator
Heidelberg University