A Phase III Randomized Trial of Low-Dose Versus Standard-Dose mBACOD Chemotherapy With rGM-CSF for Treatment of AIDS-Associated Non-Hodgkin's Lymphoma

To determine the impact of dose intensity on tumor response and survival in patients with HIV-associated non-Hodgkin's lymphoma (NHL). HIV-infected patients are at increased risk for developing intermediate and high-grade NHL. While combination chemotherapy for aggressive B-cell NHL in the absence of immunodeficiency is highly effective, the outcome of therapy for patients with AIDS-associated NHL has been disappointing. Treatment is frequently complicated by the occurrence of multiple opportunistic infections, as well as the presence of poor bone marrow reserve, making the administration of standard doses of chemotherapy difficult. A recent study was completed using a low-dose modification of the standard mBACOD (cyclophosphamide, doxorubicin, vincristine, bleomycin, dexamethasone, methotrexate ) treatment. A 46 percent response rate was observed in patients treated with this combination of chemotherapeutic agents, with a number of durable remissions and reduced toxicity when compared to previous experience with more standard treatments. A subsequent study showed similar effectiveness using a lower dose of methotrexate administered on day 15. It is hoped that the use of sargramostim (granulocyte-macrophage colony-stimulating factor; GM-CSF) will improve bone marrow function and allow for administration of a higher dose of chemotherapy.

Sex

All

Minimum age

12 Years

Inclusion Criteria

Concurrent Medication:

Required:

* PCP prophylaxis with Bactrim, aerosolized pentamidine, or dapsone.

Allowed:

ddI, except when patient is also taking allopurinol.

Patients must have the following:

* Diagnosis of HIV seropositivity and non-Hodgkin's lymphoma.
* Ability to give informed consent and willingness to comply with all procedures and visit schedule.
* If between ages of 12 and 18 must receive care under direct supervision of a pediatric oncologist, and have consent of parent, guardian, or person with power of attorney.
* Participation in clinical trials of other antiretroviral agents is at the discretion of the investigator and individual patient.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

* Active opportunistic infection, excluding Mycobacterium avium complex, requiring antibiotic therapy.
* Another prior or current malignancy, excepting curatively treated cervical or basal cell carcinoma.
* Kaposi's sarcoma if rapidly progressive, with visceral involvement, or causing peripheral edema.
* Primary central nervous system lymphoma.

Concurrent Medication:

Excluded:

* Zidovudine (AZT) or any antiretroviral agent unless allowed by investigator. ddI is allowed except when also taking allopurinol.

Systemic myelosuppressive drugs, including trimethoprim/sulfamethoxazole (T/S), pyrimethamine/sulfa, or ganciclovir.

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Patients with the following are excluded:

* Active opportunistic infection, excluding Mycobacterium avium complex, requiring antibiotic therapy.
* Another prior or current malignancy, excepting curatively treated cervical or basal cell carcinoma.
* Kaposi's sarcoma if rapidly progressive, with visceral involvement, or causing peripheral edema.
* Primary central nervous system lymphoma.

Prior Medication:

Excluded:

* Immunomodulating agents within 2 weeks of study entry.

Prior Treatment:

Excluded:

* Chemotherapy.

Radiation therapy as outlined in protocol.

• BACKGROUNDKaplan LD, Straus DJ, Testa MA, Von Roenn J, Dezube BJ, Cooley TP, Herndier B, Northfelt DW, Huang J, Tulpule A, Levine AM. Low-dose compared with standard-dose m-BACOD chemotherapy for non-Hodgkin's lymphoma associated with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med. 1997 Jun 5;336(23):1641-8. doi: 10.1056/NEJM199706053362304. PMID 9171066
• BACKGROUNDKaplan L, et al. Randomized trial of standard dose mBACOD with GM-CSF vs reduced dose mBACOD for systemic HIV-associated lymphoma: ACTG 142. Proc Annu Meet Am Assoc Cancer Res. 1995;14:A818
• BACKGROUNDStraus DJ, Huang J, Testa MA, Levine AM, Kaplan LD. Prognostic factors in the treatment of human immunodeficiency virus-associated non-Hodgkin's lymphoma: analysis of AIDS Clinical Trials Group protocol 142--low-dose versus standard-dose m-BACOD plus granulocyte-macrophage colony-stimulating factor. National Institute of Allergy and Infectious Diseases. J Clin Oncol. 1998 Nov;16(11):3601-6. doi: 10.1200/JCO.1998.16.11.3601. PMID 9817281