RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating patients with AIDS -related lymphoma.

Condition	Treatment or Intervention	Phase
AIDS-related diffuse small cleaved cell lymphoma AIDS-related small noncleaved cell lymphoma AIDS-related diffuse mixed cell lymphoma AIDS-related primary CNS lymphoma AIDS-related immunoblastic large cell lymphoma AIDS-related peripheral/systemic lymphoma AIDS-related diffuse large cell lymphoma	Drug: bleomycin  Drug: cisplatin  Drug: co-trimoxazole  Drug: cyclophosphamide  Drug: cytarabine  Drug: doxorubicin  Drug: etoposide  Drug: filgrastim  Drug: fluorouracil  Drug: ifosfamide  Drug: leucovorin calcium  Drug: mesna  Drug: methotrexate  Drug: methylprednisolone  Drug: pentamidine  Drug: prednisone  Drug: vincristine  Drug: zidovudine	Phase II

Further Study Details: 

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.

PROTOCOL 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.

Ages Eligible for Study:  15 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Previously untreated, HIV-related intermediate- and high-grade lymphoma with no previous diagnosis of Kaposi's sarcoma; Pathology reviewed at M.D. Anderson Cancer Center

--Prior/Concurrent Therapy--

• No prior therapy for lymphoma; No concurrent chemotherapy

--Patient Characteristics--

• Age: Over 15
• Performance status: Not specified
• Hematopoietic: Not specified
• Hepatic: Not specified
• Renal: For patients with T4 less than 200 and those with primary brain lymphoma: Creatinine no greater than 2.0 mg/dL (unless entry approved by principal investigator)
• Other: Serious intercurrent illness must be discussed with the principal investigator; Infectious disease consultation required for complex infections; Medications for other conditions allowed provided no adverse interaction with protocol therapy occurs; No previously diagnosed Kaposi's sarcoma or other malignancy

Florida
      MD Anderson Cancer Center Orlando, Orlando,  Florida,  32806,  United States
Texas
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030,  United States

Study chairs or principal investigators

Peter McLaughlin,  Study Chair,  M.D. Anderson Cancer Center   

Study ID Numbers:  CDR0000078316; MDA-DM-93058; NCI-T93-0088D
Record last reviewed:  October 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002524
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08