Study of Promace-Cytabom With Trimethoprim Sulfamethoxazole, Zidovudine (AZT), and Granulocyte Colony Stimulating Factor (G-CSF) in Patients With AIDS-Related Lymphoma, Phase II

Trial Information

Study of Promace-Cytabom With Trimethoprim Sulfamethoxazole, Zidovudine (AZT), and Granulocyte Colony Stimulating Factor (G-CSF) in Patients With AIDS-Related Lymphoma, Phase II

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.