Standard Chemotherapy (CHOP Regimen) Versus Sequential High-Dose Chemotherapy With Autologous Stem Cell Transplantation in Patients With Newly Diagnosed Aggressive Non-Hodgkin's Lymphomas and Poor Prognostic Factors: A Randomized Phase III Study (MISTRAL)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 400
- 试验地点
- 24
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining peripheral stem cell transplantation with more than one drug regimen may kill more tumor cells. It is not known whether receiving standard combination chemotherapy alone is more effective than receiving multiple combination chemotherapy plus peripheral stem cell transplantation for aggressive non-Hodgkin's lymphoma.
PURPOSE: This randomized phase III trial is comparing giving different combination chemotherapy regimens together with peripheral stem cell transplantation to see how well they work in treating patients with newly diagnosed aggressive non-Hodgkin's lymphoma.
详细描述
OBJECTIVES:
- Compare the efficacy of sequential high-dose chemotherapy and autologous peripheral blood stem cell transplantation with standard chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with newly diagnosed aggressive non-Hodgkin's lymphoma and poor prognostic factors.
- Compare the toxic effects of these 2 regimens in these patients.
- Compare the response rates and overall survival of patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of two treatment arms.
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Arm I: Patients receive standard chemotherapy comprising cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Patients receive cyclophosphamide IV over 30 minutes, doxorubicin IV, and vincristine IV on day 1. Patients receive oral prednisone daily on days 1-5. Treatment repeats every 21 days for 6-8 courses. Patients with bulky disease at diagnosis or residual disease after chemotherapy receive radiotherapy 30-60 days after initiation of the last course of CHOP.
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Arm II: Patients receive 5 regimens of chemotherapy administered in sequence.
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Regimen A : Patients receive CHOP as in Arm I.
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Regimen B: Three weeks after starting regimen A, patients receive high-dose cyclophosphamide IV over 24 hours on day 1. Patients without initial bone marrow involvement receive filgrastim (G-CSF) subcutaneously (SC) daily beginning on day 3 and continuing until autologous peripheral blood stem cells (PBSC) are harvested. PBSC are harvested on days 13-15 or when blood counts recover. Patients with initial bone marrow involvement do not undergo harvest of PBSC at this time, but receive G-CSF SC daily.
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Regimen C: Two to three weeks after high-dose cyclophosphamide, patients receive vincristine IV and high-dose methotrexate IV over 6 hours on day 2. Patients receive leucovorin calcium IV every 6 hours on days 3-5 beginning 24 hours after initiation of the methotrexate infusion.
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Regimen D: Within 1-2 weeks after the administration of methotrexate in regimen C, patients receive methylprednisolone IV followed 6 hours later by high-dose etoposide IV over 10 hours on day 1. Patients receive methylprednisolone IV on day 2. Patients without initial bone marrow involvement receive G-CSF SC daily beginning on day 3 and continuing until blood counts recover. Patients with initial bone marrow involvement receive G-CSF SC daily until autologous PBSC are harvested. PBSC are harvested on days 10-14 or when blood counts recover.
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Regimen E: Myeloablative therapy and autologous PBSC transplantation begin 16-40 days after the administration of etoposide. Patients receive mitoxantrone IV over 1 hour every 2 hours for 3 doses on day 2 and melphalan IV over 30 minutes on day 5. PBSC are reinfused on day 6 beginning at least 24 hours after the administration of melphalan. Patients receive G-CSF SC or by continuous infusion beginning on day 7.
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
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed aggressive non-Hodgkin's lymphoma (NHL)
- •Diffuse large B-cell lymphoma
- •Primary mediastinal large B-cell lymphoma
- •Anaplastic large cell lymphoma (B-cell, T-cell, or null-cell type)
- •At least two of the following risk factors:
- •Stage III or IV
- •LDH greater than upper limit of normal (ULN)
- •ECOG 2, 3, or 4
- •No CNS involvement
- •PATIENT CHARACTERISTICS:
- •Performance status:
- •See Disease Characteristics
- •Life expectancy:
- •Not specified
- •Hematopoietic:
- •Not specified
- •No hepatitis B or C
- •AST or ALT no greater than 2 times ULN*
- •Bilirubin no greater than 2.34 mg/dL* NOTE: *Unless due to tumor involvement
- •Creatinine clearance at least 60 mL/min (unless due to tumor involvement)
- •Cardiovascular:
- •No significant heart failure
- •LVEF normal
- •No active angina pectoris
- •No myocardial infarction within the past 6 months
- •No major ventricular arrhythmia
- •No significant lung disorder
- •HIV negative
- •No severe active acute or chronic infection
- •No severe psychoses
- •No prior or concurrent malignancy except adequately treated carcinoma in situ of the cervix or nonmelanomatous skin cancer
- •Not pregnant or nursing
- •Fertile patients must use effective contraception
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy:
- •Not specified
- •Chemotherapy:
- •No prior chemotherapy for NHL (except emergency therapy, but no more than 1 course of standard chemotherapy)
- •Endocrine therapy:
- •Not specified
- •Radiotherapy:
- •No prior radiotherapy for NHL (except emergency therapy of no greater than 600 cGy radiation)
- •No concurrent prophylactic radiotherapy to the brain
- •Not specified
排除标准
- 未提供