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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

Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Lymphoma, Non-Hodgkin; HIV Infections

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

Phase: Phase 3

Status: Completed

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
L Kaplan, Study Chair
AA Levine, Study Chair
DJ Straus, Study Chair

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 Details

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

Study design: Masking: Open Label, Primary Purpose: Treatment

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

Minimum age: 12 Years. Maximum age: N/A. Gender(s): Both.

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.

Locations and Contacts

UCLA CARE Center CRS, Los Angeles, California 90095, United States

USC CRS, Los Angeles, California 900331079, United States

Ucsf Aids Crs, San Francisco, California 941102859, United States

University of Colorado Hospital CRS, Aurora, Colorado 80262, United States

Northwestern University CRS, Chicago, Illinois 60611, United States

Rush Univ. Med. Ctr. ACTG CRS, Chicago, Illinois 60612, United States

Indiana Univ. School of Medicine, Infectious Disease Research Clinic, Indianapolis, Indiana 462025250, United States

Johns Hopkins Adult AIDS CRS, Baltimore, Maryland, United States

Beth Israel Deaconess - East Campus A0102 CRS, Boston, Massachusetts 02215, United States

Beth Israel Deaconess Med. Ctr., ACTG CRS, Boston, Massachusetts 02118, United States

Bmc Actg Crs, Boston, Massachusetts, United States

Washington U CRS, St. Louis, Missouri, United States

SUNY - Buffalo, Erie County Medical Ctr., Buffalo, New York 14215, United States

Beth Israel Med. Ctr. (Mt. Sinai), New York, New York 02215, United States

Memorial Sloan-Kettering Cancer Ctr., New York, New York 10021, United States

NY Univ. HIV/AIDS CRS, New York, New York 10016, United States

Univ. of Rochester ACTG CRS, Rochester, New York 14642, United States

Unc Aids Crs, Chapel Hill, North Carolina 275997215, United States

Case CRS, Cleveland, Ohio, United States

The Ohio State Univ. AIDS CRS, Columbus, Ohio 432101228, United States

Hosp. of the Univ. of Pennsylvania CRS, Philadelphia, Pennsylvania 19104, United States

Pitt CRS, Pittsburgh, Pennsylvania 15213, United States

Additional Information

Related publications:

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.

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

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.


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Page last updated: August 23, 2015

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