Study of Promace-Cytabom With Trimethoprim Sulfamethoxazole, Zidovudine (AZT), and Granulocyte Colony Stimulating Factor (G-CSF) in Patients With AIDS-Related Lymphoma, Phase II
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 85
- 主要终点
- Response
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Antiviral therapy may be effective treatment for AIDS-related lymphoma.
PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy, radiation therapy, and antiviral therapy in treating patients who have AIDS-related lymphoma.
详细描述
OBJECTIVES: I. Assess the response rate of AIDS-related lymphoma to ProMACE-CytaBOM (cyclophosphamide, doxorubicin, etoposide, prednisone, cytarabine, bleomycin, vincristine, methotrexate). II. Assess the toxic effects of ProMACE-CytaBOM in patients with AIDS-related lymphoma. III. Evaluate whether the incorporation of filgrastim (G-CSF) into the regimen allows treatment with full doses of the myelotoxic agents in these patients. IV. Determine whether intensive CNS treatment with intrathecal cytarabine and whole-brain irradiation prevents meningeal relapse or controls meningeal lymphomatous involvement in these patients.
OUTLINE: Patients are stratified according to participating institution and descriptive factors: histopathology (diffuse large cleaved/noncleaved and immunoblastic lymphomas vs all others), CD4 count (less than 50 vs 50 or more cells/mm3), prior opportunistic infection (yes vs no), performance status (0 and 1 vs 2), concurrent AZT (yes vs no), concurrent protease inhibitors (yes vs no), marrow involvement (yes vs no). Patients receive ProMACE-CytaBOM regimen as follows: Cyclophosphamide, doxorubicin, and etoposide IV on day 1 Cytarabine, bleomycin, vincristine, and methotrexate IV on day 8 Oral prednisone on days 1-14 Oral leucovorin calcium every 6 hours for 4 doses on day 9 Patients also receive filgrastim (G-CSF) subcutaneously on days 9-20 and oral co-trimoxazole 3 days a week throughout treatment, plus antiretroviral therapy at the discretion of the treating physician. Treatment repeats every 21 days for a maximum of 6 courses. Patients with progressive disease are removed from study after 2 courses. Remaining patients receive an additional 2 treatment courses and are then restaged. Patients without stable or progressive disease receive 2 more courses in the absence of unacceptable toxicity. Patients with positive bone marrow at study entry receive CNS prophylaxis with 5 evenly spaced doses of intrathecal cytarabine during the first 2 treatment courses and on day 1 of each subsequent course. Patients with positive CSF cytology at study entry receive intrathecal cytarabine on days 1-5 of the first treatment course and on day 1 of each subsequent course if CSF negative after 5 daily doses. Patients whose CSF remains positive after 5 days receive 5 evenly spaced doses of intrathecal methotrexate during the second treatment course. Patients with negative bone marrow and CSF cytology at study entry receive 5 evenly spaced doses of intrathecal cytarabine within 1 month of systemic therapy. All patients achieving a complete or partial response following systemic therapy and intrathecal cytarabine receive cranial irradiation to all meningeal surfaces. Patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, then annually thereafter.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study over approximately 2 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
ProMACE-CytaBOM + G-CSF
6 cycles of 21 days each of ProMACE-CytaBOM (cyclophosphamide 490 mg/m^2 on day 1, doxorubicin 19 mg/m^2 on day 1, etoposide 90 mg/m^2 on day 1, cytarabine 225 mg/m^2 on day 8, bleomycin 5 u/m^2 on day 8, methotrexate 90 mg/m^2 on day 8, leucovorin 25 mg/m^2 q 6 hours on days 8-9, vincristine 1.4 mg/m^2 on day 8, prednisone 60 mg/m^2 on days 1-14, allopurinol 300 mg on days 1-21 of cycle 1 and days 1-8 of cycle 2 only) plus 1 double strength tablet TMP/SMX 3 days a week plus G-CSF 5 ug/kg on days 9-20. Patients also receive intrathecal cytarabine 30 mg/m^2 (BM positive: 5 doses spaced evenly during 1st 2 cycles, then on day 1 of cycles 3-6; CSF cytology positive: 5 doses spaced evenly during 1st cycle, then on day 1 of cycles 2-6; BM and CSF negative: 5 doses spaced evenly within 1 month of completion of cycle 6). All patients with CR or PR after systemic therapy and IT cytarabine receive 2400 cGy RT to the whole brain in 12 fractions.
干预措施: bleomycin sulfate (Biological)
ProMACE-CytaBOM + G-CSF
6 cycles of 21 days each of ProMACE-CytaBOM (cyclophosphamide 490 mg/m^2 on day 1, doxorubicin 19 mg/m^2 on day 1, etoposide 90 mg/m^2 on day 1, cytarabine 225 mg/m^2 on day 8, bleomycin 5 u/m^2 on day 8, methotrexate 90 mg/m^2 on day 8, leucovorin 25 mg/m^2 q 6 hours on days 8-9, vincristine 1.4 mg/m^2 on day 8, prednisone 60 mg/m^2 on days 1-14, allopurinol 300 mg on days 1-21 of cycle 1 and days 1-8 of cycle 2 only) plus 1 double strength tablet TMP/SMX 3 days a week plus G-CSF 5 ug/kg on days 9-20. Patients also receive intrathecal cytarabine 30 mg/m^2 (BM positive: 5 doses spaced evenly during 1st 2 cycles, then on day 1 of cycles 3-6; CSF cytology positive: 5 doses spaced evenly during 1st cycle, then on day 1 of cycles 2-6; BM and CSF negative: 5 doses spaced evenly within 1 month of completion of cycle 6). All patients with CR or PR after systemic therapy and IT cytarabine receive 2400 cGy RT to the whole brain in 12 fractions.
干预措施: filgrastim (Biological)
ProMACE-CytaBOM + G-CSF
6 cycles of 21 days each of ProMACE-CytaBOM (cyclophosphamide 490 mg/m^2 on day 1, doxorubicin 19 mg/m^2 on day 1, etoposide 90 mg/m^2 on day 1, cytarabine 225 mg/m^2 on day 8, bleomycin 5 u/m^2 on day 8, methotrexate 90 mg/m^2 on day 8, leucovorin 25 mg/m^2 q 6 hours on days 8-9, vincristine 1.4 mg/m^2 on day 8, prednisone 60 mg/m^2 on days 1-14, allopurinol 300 mg on days 1-21 of cycle 1 and days 1-8 of cycle 2 only) plus 1 double strength tablet TMP/SMX 3 days a week plus G-CSF 5 ug/kg on days 9-20. Patients also receive intrathecal cytarabine 30 mg/m^2 (BM positive: 5 doses spaced evenly during 1st 2 cycles, then on day 1 of cycles 3-6; CSF cytology positive: 5 doses spaced evenly during 1st cycle, then on day 1 of cycles 2-6; BM and CSF negative: 5 doses spaced evenly within 1 month of completion of cycle 6). All patients with CR or PR after systemic therapy and IT cytarabine receive 2400 cGy RT to the whole brain in 12 fractions.
干预措施: cyclophosphamide (Drug)
ProMACE-CytaBOM + G-CSF
6 cycles of 21 days each of ProMACE-CytaBOM (cyclophosphamide 490 mg/m^2 on day 1, doxorubicin 19 mg/m^2 on day 1, etoposide 90 mg/m^2 on day 1, cytarabine 225 mg/m^2 on day 8, bleomycin 5 u/m^2 on day 8, methotrexate 90 mg/m^2 on day 8, leucovorin 25 mg/m^2 q 6 hours on days 8-9, vincristine 1.4 mg/m^2 on day 8, prednisone 60 mg/m^2 on days 1-14, allopurinol 300 mg on days 1-21 of cycle 1 and days 1-8 of cycle 2 only) plus 1 double strength tablet TMP/SMX 3 days a week plus G-CSF 5 ug/kg on days 9-20. Patients also receive intrathecal cytarabine 30 mg/m^2 (BM positive: 5 doses spaced evenly during 1st 2 cycles, then on day 1 of cycles 3-6; CSF cytology positive: 5 doses spaced evenly during 1st cycle, then on day 1 of cycles 2-6; BM and CSF negative: 5 doses spaced evenly within 1 month of completion of cycle 6). All patients with CR or PR after systemic therapy and IT cytarabine receive 2400 cGy RT to the whole brain in 12 fractions.
干预措施: cytarabine (Drug)
ProMACE-CytaBOM + G-CSF
6 cycles of 21 days each of ProMACE-CytaBOM (cyclophosphamide 490 mg/m^2 on day 1, doxorubicin 19 mg/m^2 on day 1, etoposide 90 mg/m^2 on day 1, cytarabine 225 mg/m^2 on day 8, bleomycin 5 u/m^2 on day 8, methotrexate 90 mg/m^2 on day 8, leucovorin 25 mg/m^2 q 6 hours on days 8-9, vincristine 1.4 mg/m^2 on day 8, prednisone 60 mg/m^2 on days 1-14, allopurinol 300 mg on days 1-21 of cycle 1 and days 1-8 of cycle 2 only) plus 1 double strength tablet TMP/SMX 3 days a week plus G-CSF 5 ug/kg on days 9-20. Patients also receive intrathecal cytarabine 30 mg/m^2 (BM positive: 5 doses spaced evenly during 1st 2 cycles, then on day 1 of cycles 3-6; CSF cytology positive: 5 doses spaced evenly during 1st cycle, then on day 1 of cycles 2-6; BM and CSF negative: 5 doses spaced evenly within 1 month of completion of cycle 6). All patients with CR or PR after systemic therapy and IT cytarabine receive 2400 cGy RT to the whole brain in 12 fractions.
干预措施: doxorubicin hydrochloride (Drug)
ProMACE-CytaBOM + G-CSF
6 cycles of 21 days each of ProMACE-CytaBOM (cyclophosphamide 490 mg/m^2 on day 1, doxorubicin 19 mg/m^2 on day 1, etoposide 90 mg/m^2 on day 1, cytarabine 225 mg/m^2 on day 8, bleomycin 5 u/m^2 on day 8, methotrexate 90 mg/m^2 on day 8, leucovorin 25 mg/m^2 q 6 hours on days 8-9, vincristine 1.4 mg/m^2 on day 8, prednisone 60 mg/m^2 on days 1-14, allopurinol 300 mg on days 1-21 of cycle 1 and days 1-8 of cycle 2 only) plus 1 double strength tablet TMP/SMX 3 days a week plus G-CSF 5 ug/kg on days 9-20. Patients also receive intrathecal cytarabine 30 mg/m^2 (BM positive: 5 doses spaced evenly during 1st 2 cycles, then on day 1 of cycles 3-6; CSF cytology positive: 5 doses spaced evenly during 1st cycle, then on day 1 of cycles 2-6; BM and CSF negative: 5 doses spaced evenly within 1 month of completion of cycle 6). All patients with CR or PR after systemic therapy and IT cytarabine receive 2400 cGy RT to the whole brain in 12 fractions.
干预措施: etoposide (Drug)
ProMACE-CytaBOM + G-CSF
6 cycles of 21 days each of ProMACE-CytaBOM (cyclophosphamide 490 mg/m^2 on day 1, doxorubicin 19 mg/m^2 on day 1, etoposide 90 mg/m^2 on day 1, cytarabine 225 mg/m^2 on day 8, bleomycin 5 u/m^2 on day 8, methotrexate 90 mg/m^2 on day 8, leucovorin 25 mg/m^2 q 6 hours on days 8-9, vincristine 1.4 mg/m^2 on day 8, prednisone 60 mg/m^2 on days 1-14, allopurinol 300 mg on days 1-21 of cycle 1 and days 1-8 of cycle 2 only) plus 1 double strength tablet TMP/SMX 3 days a week plus G-CSF 5 ug/kg on days 9-20. Patients also receive intrathecal cytarabine 30 mg/m^2 (BM positive: 5 doses spaced evenly during 1st 2 cycles, then on day 1 of cycles 3-6; CSF cytology positive: 5 doses spaced evenly during 1st cycle, then on day 1 of cycles 2-6; BM and CSF negative: 5 doses spaced evenly within 1 month of completion of cycle 6). All patients with CR or PR after systemic therapy and IT cytarabine receive 2400 cGy RT to the whole brain in 12 fractions.
干预措施: leucovorin calcium (Drug)
ProMACE-CytaBOM + G-CSF
6 cycles of 21 days each of ProMACE-CytaBOM (cyclophosphamide 490 mg/m^2 on day 1, doxorubicin 19 mg/m^2 on day 1, etoposide 90 mg/m^2 on day 1, cytarabine 225 mg/m^2 on day 8, bleomycin 5 u/m^2 on day 8, methotrexate 90 mg/m^2 on day 8, leucovorin 25 mg/m^2 q 6 hours on days 8-9, vincristine 1.4 mg/m^2 on day 8, prednisone 60 mg/m^2 on days 1-14, allopurinol 300 mg on days 1-21 of cycle 1 and days 1-8 of cycle 2 only) plus 1 double strength tablet TMP/SMX 3 days a week plus G-CSF 5 ug/kg on days 9-20. Patients also receive intrathecal cytarabine 30 mg/m^2 (BM positive: 5 doses spaced evenly during 1st 2 cycles, then on day 1 of cycles 3-6; CSF cytology positive: 5 doses spaced evenly during 1st cycle, then on day 1 of cycles 2-6; BM and CSF negative: 5 doses spaced evenly within 1 month of completion of cycle 6). All patients with CR or PR after systemic therapy and IT cytarabine receive 2400 cGy RT to the whole brain in 12 fractions.
干预措施: methotrexate (Drug)
ProMACE-CytaBOM + G-CSF
6 cycles of 21 days each of ProMACE-CytaBOM (cyclophosphamide 490 mg/m^2 on day 1, doxorubicin 19 mg/m^2 on day 1, etoposide 90 mg/m^2 on day 1, cytarabine 225 mg/m^2 on day 8, bleomycin 5 u/m^2 on day 8, methotrexate 90 mg/m^2 on day 8, leucovorin 25 mg/m^2 q 6 hours on days 8-9, vincristine 1.4 mg/m^2 on day 8, prednisone 60 mg/m^2 on days 1-14, allopurinol 300 mg on days 1-21 of cycle 1 and days 1-8 of cycle 2 only) plus 1 double strength tablet TMP/SMX 3 days a week plus G-CSF 5 ug/kg on days 9-20. Patients also receive intrathecal cytarabine 30 mg/m^2 (BM positive: 5 doses spaced evenly during 1st 2 cycles, then on day 1 of cycles 3-6; CSF cytology positive: 5 doses spaced evenly during 1st cycle, then on day 1 of cycles 2-6; BM and CSF negative: 5 doses spaced evenly within 1 month of completion of cycle 6). All patients with CR or PR after systemic therapy and IT cytarabine receive 2400 cGy RT to the whole brain in 12 fractions.
干预措施: prednisone (Drug)
ProMACE-CytaBOM + G-CSF
6 cycles of 21 days each of ProMACE-CytaBOM (cyclophosphamide 490 mg/m^2 on day 1, doxorubicin 19 mg/m^2 on day 1, etoposide 90 mg/m^2 on day 1, cytarabine 225 mg/m^2 on day 8, bleomycin 5 u/m^2 on day 8, methotrexate 90 mg/m^2 on day 8, leucovorin 25 mg/m^2 q 6 hours on days 8-9, vincristine 1.4 mg/m^2 on day 8, prednisone 60 mg/m^2 on days 1-14, allopurinol 300 mg on days 1-21 of cycle 1 and days 1-8 of cycle 2 only) plus 1 double strength tablet TMP/SMX 3 days a week plus G-CSF 5 ug/kg on days 9-20. Patients also receive intrathecal cytarabine 30 mg/m^2 (BM positive: 5 doses spaced evenly during 1st 2 cycles, then on day 1 of cycles 3-6; CSF cytology positive: 5 doses spaced evenly during 1st cycle, then on day 1 of cycles 2-6; BM and CSF negative: 5 doses spaced evenly within 1 month of completion of cycle 6). All patients with CR or PR after systemic therapy and IT cytarabine receive 2400 cGy RT to the whole brain in 12 fractions.
干预措施: trimethoprim-sulfamethoxazole (Drug)
ProMACE-CytaBOM + G-CSF
6 cycles of 21 days each of ProMACE-CytaBOM (cyclophosphamide 490 mg/m^2 on day 1, doxorubicin 19 mg/m^2 on day 1, etoposide 90 mg/m^2 on day 1, cytarabine 225 mg/m^2 on day 8, bleomycin 5 u/m^2 on day 8, methotrexate 90 mg/m^2 on day 8, leucovorin 25 mg/m^2 q 6 hours on days 8-9, vincristine 1.4 mg/m^2 on day 8, prednisone 60 mg/m^2 on days 1-14, allopurinol 300 mg on days 1-21 of cycle 1 and days 1-8 of cycle 2 only) plus 1 double strength tablet TMP/SMX 3 days a week plus G-CSF 5 ug/kg on days 9-20. Patients also receive intrathecal cytarabine 30 mg/m^2 (BM positive: 5 doses spaced evenly during 1st 2 cycles, then on day 1 of cycles 3-6; CSF cytology positive: 5 doses spaced evenly during 1st cycle, then on day 1 of cycles 2-6; BM and CSF negative: 5 doses spaced evenly within 1 month of completion of cycle 6). All patients with CR or PR after systemic therapy and IT cytarabine receive 2400 cGy RT to the whole brain in 12 fractions.
干预措施: vincristine sulfate (Drug)
ProMACE-CytaBOM + G-CSF
6 cycles of 21 days each of ProMACE-CytaBOM (cyclophosphamide 490 mg/m^2 on day 1, doxorubicin 19 mg/m^2 on day 1, etoposide 90 mg/m^2 on day 1, cytarabine 225 mg/m^2 on day 8, bleomycin 5 u/m^2 on day 8, methotrexate 90 mg/m^2 on day 8, leucovorin 25 mg/m^2 q 6 hours on days 8-9, vincristine 1.4 mg/m^2 on day 8, prednisone 60 mg/m^2 on days 1-14, allopurinol 300 mg on days 1-21 of cycle 1 and days 1-8 of cycle 2 only) plus 1 double strength tablet TMP/SMX 3 days a week plus G-CSF 5 ug/kg on days 9-20. Patients also receive intrathecal cytarabine 30 mg/m^2 (BM positive: 5 doses spaced evenly during 1st 2 cycles, then on day 1 of cycles 3-6; CSF cytology positive: 5 doses spaced evenly during 1st cycle, then on day 1 of cycles 2-6; BM and CSF negative: 5 doses spaced evenly within 1 month of completion of cycle 6). All patients with CR or PR after systemic therapy and IT cytarabine receive 2400 cGy RT to the whole brain in 12 fractions.
干预措施: radiation therapy (Radiation)
ProMACE-CytaBOM + G-CSF
6 cycles of 21 days each of ProMACE-CytaBOM (cyclophosphamide 490 mg/m^2 on day 1, doxorubicin 19 mg/m^2 on day 1, etoposide 90 mg/m^2 on day 1, cytarabine 225 mg/m^2 on day 8, bleomycin 5 u/m^2 on day 8, methotrexate 90 mg/m^2 on day 8, leucovorin 25 mg/m^2 q 6 hours on days 8-9, vincristine 1.4 mg/m^2 on day 8, prednisone 60 mg/m^2 on days 1-14, allopurinol 300 mg on days 1-21 of cycle 1 and days 1-8 of cycle 2 only) plus 1 double strength tablet TMP/SMX 3 days a week plus G-CSF 5 ug/kg on days 9-20. Patients also receive intrathecal cytarabine 30 mg/m^2 (BM positive: 5 doses spaced evenly during 1st 2 cycles, then on day 1 of cycles 3-6; CSF cytology positive: 5 doses spaced evenly during 1st cycle, then on day 1 of cycles 2-6; BM and CSF negative: 5 doses spaced evenly within 1 month of completion of cycle 6). All patients with CR or PR after systemic therapy and IT cytarabine receive 2400 cGy RT to the whole brain in 12 fractions.
干预措施: Intrathecal cytarabine (Drug)
结局指标
主要结局
Response
时间窗: every 3 months while on protocol treatment
次要结局
未报告次要终点