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

NCT ID: NCT00000658

Last Updated: 2021-11-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

250 participants

Study Classification

INTERVENTIONAL

Study Completion Date

1996-02-29

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Lymphoma, Non-Hodgkin HIV Infections

Keywords

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M-BACOD protocol Granulocyte-Macrophage Colony-Stimulating Factor Acquired Immunodeficiency Syndrome Allopurinol Antineoplastic Agents, Combined

Study Design

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Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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Bleomycin sulfate

Intervention Type DRUG

Vincristine sulfate

Intervention Type DRUG

Doxorubicin hydrochloride

Intervention Type DRUG

Cyclophosphamide

Intervention Type DRUG

Allopurinol

Intervention Type DRUG

Methotrexate

Intervention Type DRUG

Cytarabine

Intervention Type DRUG

Leucovorin calcium

Intervention Type DRUG

Sargramostim

Intervention Type DRUG

Dexamethasone

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Schering-Plough

INDUSTRY

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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L Kaplan

Role: STUDY_CHAIR

AA Levine

Role: STUDY_CHAIR

DJ Straus

Role: STUDY_CHAIR

Locations

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USC CRS

Los Angeles, California, United States

Site Status

UCLA CARE Center CRS

Los Angeles, California, United States

Site Status

Ucsf Aids Crs

San Francisco, California, United States

Site Status

University of Colorado Hospital CRS

Aurora, Colorado, United States

Site Status

Northwestern University CRS

Chicago, Illinois, United States

Site Status

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, United States

Site Status

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, United States

Site Status

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, United States

Site Status

Beth Israel Deaconess Med. Ctr., ACTG CRS

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess - East Campus A0102 CRS

Boston, Massachusetts, United States

Site Status

Bmc Actg Crs

Boston, Massachusetts, United States

Site Status

Washington U CRS

St Louis, Missouri, United States

Site Status

SUNY - Buffalo, Erie County Medical Ctr.

Buffalo, New York, United States

Site Status

Beth Israel Med. Ctr. (Mt. Sinai)

New York, New York, United States

Site Status

NY Univ. HIV/AIDS CRS

New York, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Ctr.

New York, New York, United States

Site Status

Univ. of Rochester ACTG CRS

Rochester, New York, United States

Site Status

Unc Aids Crs

Chapel Hill, North Carolina, United States

Site Status

Case CRS

Cleveland, Ohio, United States

Site Status

The Ohio State Univ. AIDS CRS

Columbus, Ohio, United States

Site Status

Hosp. of the Univ. of Pennsylvania CRS

Philadelphia, Pennsylvania, United States

Site Status

Pitt CRS

Pittsburgh, Pennsylvania, United States

Site Status

Countries

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United States

References

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Kaplan 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.

Reference Type BACKGROUND
PMID: 9171066 (View on PubMed)

Kaplan 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

Reference Type BACKGROUND

Straus 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.

Reference Type BACKGROUND
PMID: 9817281 (View on PubMed)

Other Identifiers

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11117

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 142

Identifier Type: -

Identifier Source: org_study_id