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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000658

Collaborator

Schering-Plough (Industry)

250

Enrollment

Locations

11.4

Patients Per Site

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Non-Hodgkin HIV Infections	Drug: Bleomycin sulfate Drug: Vincristine sulfate Drug: Doxorubicin hydrochloride Drug: Cyclophosphamide Drug: Allopurinol Drug: Methotrexate Drug: Cytarabine Drug: Leucovorin calcium Drug: Sargramostim Drug: Dexamethasone	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Completion Date :

Feb 1, 1996

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USC CRS	Los Angeles	California	United States	900331079
2	UCLA CARE Center CRS	Los Angeles	California	United States	90095
3	Ucsf Aids Crs	San Francisco	California	United States	941102859
4	University of Colorado Hospital CRS	Aurora	Colorado	United States	80262
5	Northwestern University CRS	Chicago	Illinois	United States	60611
6	Rush Univ. Med. Ctr. ACTG CRS	Chicago	Illinois	United States	60612
7	Indiana Univ. School of Medicine, Infectious Disease Research Clinic	Indianapolis	Indiana	United States	462025250
8	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland	United States
9	Beth Israel Deaconess Med. Ctr., ACTG CRS	Boston	Massachusetts	United States	02118
10	Beth Israel Deaconess - East Campus A0102 CRS	Boston	Massachusetts	United States	02215
11	Bmc Actg Crs	Boston	Massachusetts	United States
12	Washington U CRS	Saint Louis	Missouri	United States
13	SUNY - Buffalo, Erie County Medical Ctr.	Buffalo	New York	United States	14215
14	Beth Israel Med. Ctr. (Mt. Sinai)	New York	New York	United States	02215
15	NY Univ. HIV/AIDS CRS	New York	New York	United States	10016
16	Memorial Sloan-Kettering Cancer Ctr.	New York	New York	United States	10021
17	Univ. of Rochester ACTG CRS	Rochester	New York	United States	14642
18	Unc Aids Crs	Chapel Hill	North Carolina	United States	275997215
19	Case CRS	Cleveland	Ohio	United States
20	The Ohio State Univ. AIDS CRS	Columbus	Ohio	United States	432101228
21	Hosp. of the Univ. of Pennsylvania CRS	Philadelphia	Pennsylvania	United States	19104
22	Pitt CRS	Pittsburgh	Pennsylvania	United States	15213