SWOG-9320 Combination Chemotherapy, Radiation Therapy, and Antiviral Therapy in Treating Patients With AIDS-Related Lymphoma
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.
Biological: bleomycin sulfate
Drug: doxorubicin hydrochloride
Drug: leucovorin calcium
Drug: vincristine sulfate
Radiation: radiation therapy
Drug: Intrathecal cytarabine
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Study of Promace-Cytabom With Trimethoprim Sulfamethoxazole, Zidovudine (AZT), and Granulocyte Colony Stimulating Factor (G-CSF) in Patients With AIDS-Related Lymphoma, Phase II|
- Response [ Time Frame: every 3 months while on protocol treatment ] [ Designated as safety issue: No ]
|Study Start Date:||June 1994|
|Study Completion Date:||July 2011|
|Primary Completion Date:||November 2003 (Final data collection date for primary outcome measure)|
Experimental: 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.
Biological: bleomycin sulfate
5u/m2 IV Q21days x 6 cyclesBiological: filgrastim
5ug/kg SC, Days 9-20, Q 21 days x 6 cycles
Other Name: G-CSFDrug: cyclophosphamide
490 mg/m2 IV Q 21 days x 6 cyclesDrug: cytarabine
225 mg/m2 IV Q 21 days x 6 cyclesDrug: doxorubicin hydrochloride
19 mg/m2 IV Q 21 days x 6 cyclesDrug: etoposide
90 mg/m2 IV Q 21 days x 6 cycles
Other Name: VP-16Drug: leucovorin calcium
25 mg/m2 po 24 hours after methotrexate Q 6 hours x 4 doses for 6 cycles.Drug: methotrexate
90 mg/m2 IV, Q 21 days x 6 cycles.Drug: prednisone
60 mg/m2 po QD x 14days for 6 cyclesDrug: trimethoprim-sulfamethoxazole
1 double throughout strength treatment tablet po on Monday, Wednesday, and Friday x 6, 21 day cycles
Other Name: TMP/SMXDrug: vincristine sulfate
1.4 mg/m2 IV Q 21 Days x 6 cyclesRadiation: radiation therapy
All patients achieving a CR or PR following systemic therapy and IT Ara-C, will receive 2,400 cGy in two hundred cGy fractions to the whole brain. Fields should adequately encompass all meningeal surfaces.Drug: Intrathecal cytarabine
If initial bone marrow positive:
Ara-C 30 mg/m2 IT per dose x 5 doses spaced evenly during the first two cycles of therapy. Ara-C 30 mg/m2 IT Day 1 of each subsequent cycle.
If initial CSF cytology positive:
Ara-C 30 mg/m2 IT per dose x 5 doses spaced evenly during the first cycle of therapy. If CSF negative after above, Ara-C 30 mg/m2 IT Day 1 of each subsequent cycle. If CSF positive after initial five doses of Ara-C, IT MTX 12 mg per dose x 5 doses should be given spaced evenly during the second cycle of therapy.
If initial bone marrow and CSF negative:
Ara-C 30 mg/m2 IT per dose x 5 doses to be given spaced evenly within 1 month of completion of systemic therapy.
Other Name: IT Ara-C
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00002571
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|Study Chair:||Lode J. Swinnen, MD||Loyola University|