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

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Completed; Phase 3

Conditions: HIV Infections; Lymphoma, Non-Hodgkin

Treatments: Drug: Allopurinol; Drug: Sargramostim; Drug: Leucovorin calcium; Drug: Cytarabine; Drug: Dexamethasone; Drug: Methotrexate; Drug: Cyclophosphamide; Drug: Doxorubicin hydrochloride; Drug: Vincristine sulfate; Drug: Bleomycin sulfate

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT00000658

ACTG 142

11117 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

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.

Patients are randomized to one of two treatment groups. Patients are stratified for (1) presence or absence of a prior AIDS diagnosis, (2) Karnofsky performance status of 70 or greater and lower than 70. Treatment includes prophylaxis for meningeal lymphoma and Pneumocystis carinii pneumonia. Patients on low-dose mBACOD who experience neutropenia may be given rGM-CSF until the absolute neutrophil count improves. AZT may be initiated at the completion of chemotherapy for all patients in complete remission at that time.

PER AMENDMENT 5/30/95: This trial was closed to accrual on 11/7/94 on the recommendation of the Data and Safety Monitoring Board (DSMB), because the non-significant difference in survival between the 2 treatment groups was not expected to change with further enrollment.

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

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.