Clinical trial NCT00000658: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lymphoma, Non-Hodgkin
HIV Infections
Keywords: M-BACOD protocol
Granulocyte-Macrophage Colony-Stimulating Factor
Acquired Immunodeficiency Syndrome
Allopurinol
Antineoplastic Agents, Combined
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Schering-Plough
First posted: 2001-08-31
Enrollment: 250
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC CRS
state: California
city: Los Angeles
country: United States
facility: UCLA CARE Center CRS
state: California
city: San Francisco
country: United States
facility: Ucsf Aids Crs
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital CRS
state: Colorado
city: Chicago
country: United States
facility: Northwestern University CRS
state: Illinois
city: Chicago
country: United States
facility: Rush Univ. Med. Ctr. ACTG CRS
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ. School of Medicine, Infectious Disease Research Clinic
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins Adult AIDS CRS
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Med. Ctr., ACTG CRS
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess - East Campus A0102 CRS
state: Massachusetts
city: Boston
country: United States
facility: Bmc Actg Crs
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington U CRS
state: Missouri
city: Buffalo
country: United States
facility: SUNY - Buffalo, Erie County Medical Ctr.
state: New York
city: New York
country: United States
facility: Beth Israel Med. Ctr. (Mt. Sinai)
state: New York
city: New York
country: United States
facility: NY Univ. HIV/AIDS CRS
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Ctr.
state: New York
city: Rochester
country: United States
facility: Univ. of Rochester ACTG CRS
state: New York
city: Chapel Hill
country: United States
facility: Unc Aids Crs
state: North Carolina
city: Cleveland
country: United States
facility: Case CRS
state: Ohio
city: Columbus
country: United States
facility: The Ohio State Univ. AIDS CRS
state: Ohio
city: Philadelphia
country: United States
facility: Hosp. of the Univ. of Pennsylvania CRS
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Pitt CRS
state: Pennsylvania
Study officials:
name: L Kaplan
role: STUDY_CHAIR
name: AA Levine
role: STUDY_CHAIR
name: DJ Straus
role: STUDY_CHAIR
References:
citation: 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.
citation: 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
citation: 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.