Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

November 2, 1999
April 26, 2012
Not Provided
Not Provided
Not Provided
Not Provided
Complete list of historical versions of study NCT00000658 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
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
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

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.

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.

Interventional
Phase 3
Masking: Open Label
Primary Purpose: Treatment
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
250
February 1996
Not Provided

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.

Both
12 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00000658
ACTG 142, 11117
Not Provided
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Schering-Plough
Study Chair: L Kaplan
Study Chair: AA Levine
Study Chair: DJ Straus
National Institute of Allergy and Infectious Diseases (NIAID)
April 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP