Pilot Study in AIDS-Related Lymphomas

Trial Information

Pilot Study in AIDS-Related Lymphomas

OBJECTIVES: I. Develop an effective chemotherapy regimen with mild immunosuppressive and
myelosuppressive properties to treat patients with AIDS-related lymphoma (ARL) who have
severe T4 lymphopenia. II. Estimate the CR rate, lymphoma-free survival, and overall
survival of non-T4 lymphopenic patients and patients who present with nonbulky Ann Arbor
stage I ARL treated with standard regimens of known effectiveness. III. Evaluate the effects
on long-term outlook of concurrent antiretroviral therapy, prophylactic antibiosis with
trimethoprim/sulfamethoxazole or aerosolized pentamidine, and prn use of granulocyte
colony-stimulating factor for severe myelosuppression.

OUTLINE: Patients are assigned to Regimens A, B, and C according to histology and extent of
disease and the degree of immunosuppression as follows: Regimen A: Patients with Ann Arbor
stage I intermediate grade or immunoblastic lymphoma with measurable nonbulky disease (less
than 7 cm), low LDH (less than 686), and no prior opportunistic infection irrespective of T4
count; also those with nonmeasurable stage I extranodal primaries (infiltration of less than
2/3 of an organ site, e.g., stomach, rectum, esophagus, sinus cavity) irrespective of T4
count. Regimen B: All patients (except primary brain lymphoma patients) not assigned to
Regimen A who have T4 counts of at least 200 and no history of opportunistic infection;
includes all stages of small noncleaved cell lymphoma and bulky stage I and stages II-IV
intermediate grade and immunoblastic lymphoma. Regimen C: Patients not assigned to Regimen A
or B, i.e., those with T4 counts less than 200 and/or a history of opportunistic infection
and those with primary brain lymphoma. The following acronyms are used: ARA-C Cytarabine,
NSC-63878 BLEO Bleomycin, NSC-125066 CDDP Cisplatin, NSC-119875 CF Leucovorin calcium,
NSC-3590 CTX Cyclophosphamide, NSC-26271 DOX Doxorubicin, NSC-123127 5-FU Fluorouracil,
NSC-19893 G-CSF Granulocyte Colony-Stimulating Factor (Amgen), NSC-614629 IFF Ifosfamide,
NSC-109723 MePRDL Methylprednisolone succinate Mesna Mercaptoethane sulfonate, NSC-113891
MTX Methotrexate, NSC-740 PRED Prednisone, NSC-10023 VCR Vincristine, NSC-67574 VP-16
Etoposide, NSC-141540 ZDV Zidovudine, NSC-602670 Regimen A: 5-Drug Combination Chemotherapy
followed by Radiotherapy. CHOP-BLEO: CTX; DOX; VCR; PRED; BLEO; followed by involved-field
irradiation with megavoltage equipment. Regimen B: 4-Drug Combination Chemotherapy
alternating with 3-Drug Combination Chemotherapy followed, as indicated, by Radiotherapy.
ASHAP: DOX; MePRDL; ARA-C; CDDP; alternating with IMVP-16: IFF/Mesna; MTX/CF; VP-16;
followed, in selected patients with initially bulky localized disease, by involved-field
irradiation with megavoltage equipment. Regimen C: 2-Drug Combination Chemotherapy with Drug
Modulation followed, as indicated, by Radiotherapy. FLEP: 5-FU/CF/CDDP; followed, in
selected patients with initially bulky localized disease, by involved-field irradiation with
megavoltage equipment. Prior to starting chemotherapy, patients with primary brain lymphoma
receive a course of cranial irradiation using accelerator beams with photon energies of 6-15
MV.

PROJECTED ACCRUAL: Up to 92 patients (10 for Regimen A, 28 for Regimen B, 54 for Regimen C)
will be entered over 3 years. If there are no CRs among the first 6 patients on Regimens A
and B or the first 19 patients on Regimen C, accrual to that regimen will cease. If more
than 4 infectious deaths occur among the first 10 patients or if the rate of disease
progression exceeds 20% on any regimen, further accrual to that regimen will cease.