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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

This study has been completed.
Sponsor:
Collaborator:
Schering-Plough
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000658
First received: November 2, 1999
Last updated: April 26, 2012
Last verified: April 2012
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Masking: 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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 250
Study Completion Date: February 1996
Detailed 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.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000658

Locations
United States, California
UCLA CARE Center CRS
Los Angeles, California, United States, 90095
USC CRS
Los Angeles, California, United States, 900331079
Ucsf Aids Crs
San Francisco, California, United States, 941102859
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States, 80262
United States, Illinois
Northwestern University CRS
Chicago, Illinois, United States, 60611
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, United States, 60612
United States, Indiana
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States, 462025250
United States, Maryland
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, United States
United States, Massachusetts
Bmc Actg Crs
Boston, Massachusetts, United States
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, United States, 02118
Beth Israel Deaconess - East Campus A0102 CRS
Boston, Massachusetts, United States, 02215
United States, Missouri
Washington U CRS
St. Louis, Missouri, United States
United States, New York
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, United States, 14215
Beth Israel Med. Ctr. (Mt. Sinai)
New York, New York, United States, 02215
Memorial Sloan-Kettering Cancer Ctr.
New York, New York, United States, 10021
NY Univ. HIV/AIDS CRS
New York, New York, United States, 10016
Univ. of Rochester ACTG CRS
Rochester, New York, United States, 14642
United States, North Carolina
Unc Aids Crs
Chapel Hill, North Carolina, United States, 275997215
United States, Ohio
Case CRS
Cleveland, Ohio, United States
The Ohio State Univ. AIDS CRS
Columbus, Ohio, United States, 432101228
United States, Pennsylvania
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, United States, 19104
Pitt CRS
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Schering-Plough
Investigators
Study Chair: L Kaplan
Study Chair: AA Levine
Study Chair: DJ Straus
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000658     History of Changes
Other Study ID Numbers: ACTG 142, 11117
Study First Received: November 2, 1999
Last Updated: April 26, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
M-BACOD protocol
Granulocyte-Macrophage Colony-Stimulating Factor
Acquired Immunodeficiency Syndrome
Allopurinol
Antineoplastic Agents, Combined

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Lymphoma
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunologic Deficiency Syndromes
Immunoproliferative Disorders
Lentivirus Infections
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Allopurinol
Bleomycin
Cyclophosphamide
Dexamethasone
Doxorubicin
Levoleucovorin
Liposomal doxorubicin
Methotrexate
Vincristine
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents

ClinicalTrials.gov processed this record on November 23, 2014