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

HIV Infections Clinical Trial

Official title: 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

Status Completed

Clinical Trial Summary

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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• HIV Infections
• Lymphoma
• Lymphoma, Non-Hodgkin

• NCT number: NCT00000658
• Study type: Interventional
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Status: Completed
• Phase: Phase 3
• Completion date: February 1996