Phase II Study of Intensive Chemotherapy and Rituximab in Burkitt Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Response Rates (CR and PR) in Adults With Burkitt/Atypical Burkitt
研究概览
简要总结
The purpose of this study is to learn more about how well a chemotherapy regime including rituximab works in treating patients with Burkitt or atypical Burkitt lymphoma.
详细描述
- Patients will be placed into one of two groups, "low risk" and "high risk". "Low risk" disease is defined as one area of disease measuring less than 10cm and a normal blood test called LDH (lactate hydrogenase). Patients not fitting the "low risk" criteria are considered "high risk".
- If the patient has "low risk" disease their treatment cycle consist of three cycles of A.
- If the patient has "high risk" disease they will receive Cycle A followed by cycle B which will then repeat.
- Cycle A consists of the drugs: rituximab, cyclophosphamide, oncovin, doxorubicin and methotrexate (R-CODOX-M). The treatment cycle is approximately 14 days. A spinal tap is performed on day 1 and day 3 of the cycle and the patient will be hospitalized until between day 11 and day 13. After the patient's blood counts return to normal(usually around day 21),the next round of treatment will occur.
- Cycle B consists of the drugs: rituximab, ifosfamide, VP-16 and ara-c (IVAC). The treatment cycle is approximately 5 days. A spinal tap is performed on day 4 and once blood counts return to normal the patient will start cycle A again.
- After the patient has finished the treatments, they will be re-evaluated with CT scans and PET scans to determine whether or not they are in remission. Every three months for two years, blood tests and CT and PET scans will be performed. Follow up after that will be every 6 months for two years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically documented Burkitt or atypical Burkitt according to World Health Organization (WHO) criteria.
- •Pathology must be reviewed at the Brigham and Women's Hospital (BWH).
- •Measurable or evaluable disease: Disease reproducibly measurable in two perpendicular dimensions on exam, computed tomography (CT), radiograph, or magnetic resonance imaging (MRI). Disease present on bone marrow biopsy will be considered as evaluable disease.
- •The following may not be used as the sole site of measurable or evaluable disease: *ascites, *pleural effusion, *bone lesion or *central nervous system (CNS) disease.
- •Age > 18
- •Laboratory data (within 2 weeks of study registration):
- •ANC > 1500/ul;
- •platelet > 100,000/ul;
- •creatinine < 1.5 X normal;
- •creatinine clearance > 60 ml/min;
- •bilirubin < 1.5 X normal;
- •AST and ALT < 2.5 X normal;
- •alkaline phosphates < 3 X normal;
- •HIV negative;
- •cardiac ejection fraction > 50%.
排除标准
- •Previous chemotherapy or radiation therapy. Steroids of less than 72 hours duration for impending oncologic emergency are allowed.
- •Uncontrolled bacterial, fungal, or viral infection.
- •Concomitant malignancy excluding carcinoma in situ of the cervix and basal cell carcinoma of the skin.
- •Serious comorbid disease. Clinically significant pulmonary symptomatology. In patients with a history of symptomatic pulmonary disease, pulmonary function tests (PFTs) should document an forced expiratory volume at 1 second (FeV1), forced vital capacity (FVC), and total lung capacity (TLC) of > 60% predicted and carbon monoxide diffusing capacity of the lung (DLCO) of > 50% predicted. No clinically significant cardiac symptomatology. The cardiac ejection fraction must be > 50%.
- •Pregnancy. All males and females with reproductive potential must consent to use an effective form of contraception while on study.
- •Major surgery within the previous 2 weeks.
研究组 & 干预措施
Low Risk
Low-risk patients receive 3 cycles of regimen A.
Regimen A:
Rituximab (375 mg/m^2) on Days 1 and 3. Cyclophosphamide (800 mg/m^2) on days 1 and 2. Vincristine (1.4 mg/m^2) on days 1 and 10. Doxorubicin (50 mg/m^2) on Day 1. Methotrexate (3000 mg/m^2) on Day 10. Intrathecal Cytarabine (50mg) will be given on Day 1 and intrathecal methotrexate (12mg) will be given on Days 1 and 10.
Leucovorin on days 11 and 12.
Rituximab is given on Days 1 and 3 in cycle 1, and on Day 1 of all other cycles.
干预措施: Rituximab (Drug)
Low Risk
Low-risk patients receive 3 cycles of regimen A.
Regimen A:
Rituximab (375 mg/m^2) on Days 1 and 3. Cyclophosphamide (800 mg/m^2) on days 1 and 2. Vincristine (1.4 mg/m^2) on days 1 and 10. Doxorubicin (50 mg/m^2) on Day 1. Methotrexate (3000 mg/m^2) on Day 10. Intrathecal Cytarabine (50mg) will be given on Day 1 and intrathecal methotrexate (12mg) will be given on Days 1 and 10.
Leucovorin on days 11 and 12.
Rituximab is given on Days 1 and 3 in cycle 1, and on Day 1 of all other cycles.
干预措施: Cyclophosphamide (Drug)
Low Risk
Low-risk patients receive 3 cycles of regimen A.
Regimen A:
Rituximab (375 mg/m^2) on Days 1 and 3. Cyclophosphamide (800 mg/m^2) on days 1 and 2. Vincristine (1.4 mg/m^2) on days 1 and 10. Doxorubicin (50 mg/m^2) on Day 1. Methotrexate (3000 mg/m^2) on Day 10. Intrathecal Cytarabine (50mg) will be given on Day 1 and intrathecal methotrexate (12mg) will be given on Days 1 and 10.
Leucovorin on days 11 and 12.
Rituximab is given on Days 1 and 3 in cycle 1, and on Day 1 of all other cycles.
干预措施: Doxorubicin (Drug)
Low Risk
Low-risk patients receive 3 cycles of regimen A.
Regimen A:
Rituximab (375 mg/m^2) on Days 1 and 3. Cyclophosphamide (800 mg/m^2) on days 1 and 2. Vincristine (1.4 mg/m^2) on days 1 and 10. Doxorubicin (50 mg/m^2) on Day 1. Methotrexate (3000 mg/m^2) on Day 10. Intrathecal Cytarabine (50mg) will be given on Day 1 and intrathecal methotrexate (12mg) will be given on Days 1 and 10.
Leucovorin on days 11 and 12.
Rituximab is given on Days 1 and 3 in cycle 1, and on Day 1 of all other cycles.
干预措施: Vincristine (Drug)
Low Risk
Low-risk patients receive 3 cycles of regimen A.
Regimen A:
Rituximab (375 mg/m^2) on Days 1 and 3. Cyclophosphamide (800 mg/m^2) on days 1 and 2. Vincristine (1.4 mg/m^2) on days 1 and 10. Doxorubicin (50 mg/m^2) on Day 1. Methotrexate (3000 mg/m^2) on Day 10. Intrathecal Cytarabine (50mg) will be given on Day 1 and intrathecal methotrexate (12mg) will be given on Days 1 and 10.
Leucovorin on days 11 and 12.
Rituximab is given on Days 1 and 3 in cycle 1, and on Day 1 of all other cycles.
干预措施: Methotrexate (Drug)
Low Risk
Low-risk patients receive 3 cycles of regimen A.
Regimen A:
Rituximab (375 mg/m^2) on Days 1 and 3. Cyclophosphamide (800 mg/m^2) on days 1 and 2. Vincristine (1.4 mg/m^2) on days 1 and 10. Doxorubicin (50 mg/m^2) on Day 1. Methotrexate (3000 mg/m^2) on Day 10. Intrathecal Cytarabine (50mg) will be given on Day 1 and intrathecal methotrexate (12mg) will be given on Days 1 and 10.
Leucovorin on days 11 and 12.
Rituximab is given on Days 1 and 3 in cycle 1, and on Day 1 of all other cycles.
干预措施: Leucovorin (Drug)
Low Risk
Low-risk patients receive 3 cycles of regimen A.
Regimen A:
Rituximab (375 mg/m^2) on Days 1 and 3. Cyclophosphamide (800 mg/m^2) on days 1 and 2. Vincristine (1.4 mg/m^2) on days 1 and 10. Doxorubicin (50 mg/m^2) on Day 1. Methotrexate (3000 mg/m^2) on Day 10. Intrathecal Cytarabine (50mg) will be given on Day 1 and intrathecal methotrexate (12mg) will be given on Days 1 and 10.
Leucovorin on days 11 and 12.
Rituximab is given on Days 1 and 3 in cycle 1, and on Day 1 of all other cycles.
干预措施: Cytarabine (Drug)
High Risk
High-risk patients receive 4 alternating cycles of regimens A and B (A-B-A-B).
Regimen A (as described earlier).
Regimen B:
Rituximab (375mg/m^2) on Day 1. Ifosfamide (1500mg/m^2) on Days 1-5. Mesna (275 mg/m^2) on Days 1-5. Etoposide (60mg/mg^2) on Days 1-5. Cytarabine (2 gm/m^2) twice a day on Days 1 and 2. Intrathecal methotrexate (12mg) on Day 5, and intrathecal methotrexate (50mg) on Day 3 (also on Day 1 for patients with central nervous system involvement).
干预措施: Rituximab (Drug)
High Risk
High-risk patients receive 4 alternating cycles of regimens A and B (A-B-A-B).
Regimen A (as described earlier).
Regimen B:
Rituximab (375mg/m^2) on Day 1. Ifosfamide (1500mg/m^2) on Days 1-5. Mesna (275 mg/m^2) on Days 1-5. Etoposide (60mg/mg^2) on Days 1-5. Cytarabine (2 gm/m^2) twice a day on Days 1 and 2. Intrathecal methotrexate (12mg) on Day 5, and intrathecal methotrexate (50mg) on Day 3 (also on Day 1 for patients with central nervous system involvement).
干预措施: Cyclophosphamide (Drug)
High Risk
High-risk patients receive 4 alternating cycles of regimens A and B (A-B-A-B).
Regimen A (as described earlier).
Regimen B:
Rituximab (375mg/m^2) on Day 1. Ifosfamide (1500mg/m^2) on Days 1-5. Mesna (275 mg/m^2) on Days 1-5. Etoposide (60mg/mg^2) on Days 1-5. Cytarabine (2 gm/m^2) twice a day on Days 1 and 2. Intrathecal methotrexate (12mg) on Day 5, and intrathecal methotrexate (50mg) on Day 3 (also on Day 1 for patients with central nervous system involvement).
干预措施: Doxorubicin (Drug)
High Risk
High-risk patients receive 4 alternating cycles of regimens A and B (A-B-A-B).
Regimen A (as described earlier).
Regimen B:
Rituximab (375mg/m^2) on Day 1. Ifosfamide (1500mg/m^2) on Days 1-5. Mesna (275 mg/m^2) on Days 1-5. Etoposide (60mg/mg^2) on Days 1-5. Cytarabine (2 gm/m^2) twice a day on Days 1 and 2. Intrathecal methotrexate (12mg) on Day 5, and intrathecal methotrexate (50mg) on Day 3 (also on Day 1 for patients with central nervous system involvement).
干预措施: Vincristine (Drug)
High Risk
High-risk patients receive 4 alternating cycles of regimens A and B (A-B-A-B).
Regimen A (as described earlier).
Regimen B:
Rituximab (375mg/m^2) on Day 1. Ifosfamide (1500mg/m^2) on Days 1-5. Mesna (275 mg/m^2) on Days 1-5. Etoposide (60mg/mg^2) on Days 1-5. Cytarabine (2 gm/m^2) twice a day on Days 1 and 2. Intrathecal methotrexate (12mg) on Day 5, and intrathecal methotrexate (50mg) on Day 3 (also on Day 1 for patients with central nervous system involvement).
干预措施: Methotrexate (Drug)
High Risk
High-risk patients receive 4 alternating cycles of regimens A and B (A-B-A-B).
Regimen A (as described earlier).
Regimen B:
Rituximab (375mg/m^2) on Day 1. Ifosfamide (1500mg/m^2) on Days 1-5. Mesna (275 mg/m^2) on Days 1-5. Etoposide (60mg/mg^2) on Days 1-5. Cytarabine (2 gm/m^2) twice a day on Days 1 and 2. Intrathecal methotrexate (12mg) on Day 5, and intrathecal methotrexate (50mg) on Day 3 (also on Day 1 for patients with central nervous system involvement).
干预措施: Leucovorin (Drug)
High Risk
High-risk patients receive 4 alternating cycles of regimens A and B (A-B-A-B).
Regimen A (as described earlier).
Regimen B:
Rituximab (375mg/m^2) on Day 1. Ifosfamide (1500mg/m^2) on Days 1-5. Mesna (275 mg/m^2) on Days 1-5. Etoposide (60mg/mg^2) on Days 1-5. Cytarabine (2 gm/m^2) twice a day on Days 1 and 2. Intrathecal methotrexate (12mg) on Day 5, and intrathecal methotrexate (50mg) on Day 3 (also on Day 1 for patients with central nervous system involvement).
干预措施: Ifosfamide (Drug)
High Risk
High-risk patients receive 4 alternating cycles of regimens A and B (A-B-A-B).
Regimen A (as described earlier).
Regimen B:
Rituximab (375mg/m^2) on Day 1. Ifosfamide (1500mg/m^2) on Days 1-5. Mesna (275 mg/m^2) on Days 1-5. Etoposide (60mg/mg^2) on Days 1-5. Cytarabine (2 gm/m^2) twice a day on Days 1 and 2. Intrathecal methotrexate (12mg) on Day 5, and intrathecal methotrexate (50mg) on Day 3 (also on Day 1 for patients with central nervous system involvement).
干预措施: Etoposide (Drug)
High Risk
High-risk patients receive 4 alternating cycles of regimens A and B (A-B-A-B).
Regimen A (as described earlier).
Regimen B:
Rituximab (375mg/m^2) on Day 1. Ifosfamide (1500mg/m^2) on Days 1-5. Mesna (275 mg/m^2) on Days 1-5. Etoposide (60mg/mg^2) on Days 1-5. Cytarabine (2 gm/m^2) twice a day on Days 1 and 2. Intrathecal methotrexate (12mg) on Day 5, and intrathecal methotrexate (50mg) on Day 3 (also on Day 1 for patients with central nervous system involvement).
干预措施: Cytarabine (Drug)
High Risk
High-risk patients receive 4 alternating cycles of regimens A and B (A-B-A-B).
Regimen A (as described earlier).
Regimen B:
Rituximab (375mg/m^2) on Day 1. Ifosfamide (1500mg/m^2) on Days 1-5. Mesna (275 mg/m^2) on Days 1-5. Etoposide (60mg/mg^2) on Days 1-5. Cytarabine (2 gm/m^2) twice a day on Days 1 and 2. Intrathecal methotrexate (12mg) on Day 5, and intrathecal methotrexate (50mg) on Day 3 (also on Day 1 for patients with central nervous system involvement).
干预措施: Mesna (Drug)
结局指标
主要结局
Response Rates (CR and PR) in Adults With Burkitt/Atypical Burkitt
时间窗: 3 years
Complete Response (CR): Disappearance of all measurable or evaluable disease confirmed. Partial Response (PR): Reduction of 50% or greater in the sum of the products of the perpendicular diameters of all measurable. Of 8 High Risk participants, 7 met the primary response outcome. 1 High Risk participant did not meet protocol defined primary outcome response and died two months following enrollment.
次要结局
- Disease Free Survival(Until disease progression up to 120 months)
研究者
Ann S. LaCasce, MD
Assistant Professor of Medicine
Dana-Farber Cancer Institute