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	Treatment or 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 III

Further Study Details: 

Expected Total Enrollment:  250

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.

Ages Eligible for Study:  12 Years and above,  Genders Eligible for Study:  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.

California
      Stanford at Kaiser / Kaiser Permanente Med Ctr, San Francisco,  California,  94115,  United States
      San Francisco Gen Hosp, San Francisco,  California,  941102859,  United States
      San Francisco AIDS Clinic / San Francisco Gen Hosp, San Francisco,  California,  941102859,  United States
      UCLA CARE Ctr, Los Angeles,  California,  90095,  United States
      Univ of Southern California / LA County USC Med Ctr, Los Angeles,  California,  900331079,  United States
      K Norris Cancer Hosp / Los Angeles County - USC Med Ctr, Los Angeles,  California,  900331079,  United States
      Huntington Memorial Hosp / Children's Hosp of Los Angeles, Pasadena,  California,  91105,  United States
      Olive View Med Ctr, Sylmar,  California,  91342,  United States
Colorado
      Univ Hosp / Univ of Colorado Health Sci Ctr, Denver,  Colorado,  80262,  United States
      Denver Dept of Health and Hosps, Denver,  Colorado,  80262,  United States
District of Columbia
      George Washington Univ Med Ctr, Washington,  District of Columbia,  20037,  United States
      Georgetown Univ Med Ctr, Washington,  District of Columbia,  20007,  United States
Illinois
      Northwestern Univ Med School, Chicago,  Illinois,  60611,  United States
      Rush Presbyterian - Saint Luke's Med Ctr, Chicago,  Illinois,  60612,  United States
      Northwestern Univ Med School, Chicago,  Illinois,  60611,  United States
Indiana
      Indiana Univ Hosp, Indianapolis,  Indiana,  462025250,  United States
Massachusetts
      Beth Israel Deaconess Med Ctr, Boston,  Massachusetts,  02215,  United States
      Beth Israel Deaconess - West Campus, Boston,  Massachusetts,  02215,  United States
      Boston Med Ctr, Boston,  Massachusetts,  02118,  United States
Michigan
      Children's Hosp of Michigan, Detroit,  Michigan,  48201,  United States
New York
      Univ of Rochester Medical Center, Rochester,  New York,  14642,  United States
      Mem Sloan - Kettering Cancer Ctr, New York,  New York,  10021,  United States
      Bellevue Hosp / New York Univ Med Ctr, New York,  New York,  10016,  United States
      Mount Sinai Med Ctr, New York,  New York,  10029,  United States
      Saint Luke's - Roosevelt Hosp Ctr, New York,  New York,  10025,  United States
      SUNY / Erie County Med Ctr at Buffalo, Buffalo,  New York,  14215,  United States
      Columbia Presbyterian Med Ctr, New York,  New York,  100323784,  United States
North Carolina
      Univ of North Carolina, Chapel Hill,  North Carolina,  275997215,  United States
Ohio
      Ohio State Univ Hosp Clinic, Columbus,  Ohio,  432101228,  United States
Pennsylvania
      Univ of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States
      Hemophilia Ctr of Western PA / Univ of Pittsburgh, Pittsburgh,  Pennsylvania,  15219,  United States
      Univ of Pennsylvania at Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States
      Univ of Pittsburgh Med School / Hershey Med Ctr, Hershey,  Pennsylvania,  170330850,  United States
      Univ of Pittsburgh Med School, Pittsburgh,  Pennsylvania,  United States
South Carolina
      Julio Arroyo, West Columbia,  South Carolina,  29169,  United States
Texas
      Univ of Texas Galveston, Galveston,  Texas,  775550435,  United States

Study chairs or principal investigators

L Kaplan,  Study Chair
AA Levine,  Study Chair
DJ Straus,  Study Chair

Study ID Numbers:  ACTG 142
Record last reviewed:  January 2003
Last Updated:  October 13, 2004
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000658
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08