This is an application for Georgetown University Medical Center and George Washington University Medical Center to jointly participate as an AIDS-associated Clinical Trials Consortium member.
The specific aims of this proposal are: 1: Demonstration of qualifications and expertise of the proposed co-investigators in the development and conduct of clinical trials in AIDS-related malignancies. 2. Demonstration of an adequate patient population between these two institutions to meet the stated minimum accrual of 30 patients/year, and commitment to place patients on these trials as the highest institutional priority. 3. Proposal of a pilot protocol involving a cytokine, chemotherapy, immunomodulator treatment regimen for AIDS-lymphomas using interleukin-4, MGBG, followed by low-dose IL-2 therapy. This proposal is based on the following observations: a. IL-4 has antitumor activity against lymphoid cell targets in vivo, and in vivo promotes a switch to a TH2 immune response pattern, and may inhibit the stimulatory activity of elevated lL-6 levels in patients with AIDS-associated lymphoma. b. MGBG has demonstrated activity as a non-myelosuppressive agent in AIDS-associated lymphomas. c. Low-dose subcutaneous lL-2 has been shown to stimulate NK-cell activity and be well tolerated in patients with AIDS-related malignancies. In an animal mode of EBV-lymphoproliferative disease low- dose IL-2 has also been shown to be associated with tumor response and decreased serum levels of IL-6 and IL-10 which may be growth stimulatory to lymphoid tumors. The hypothesis of this proposal is that manipulation of cytokines potentially involved in the initiation and progression of AIDS-associated lymphomas coupled with non-myelosuppressive chemotherapy, and immunomodulation to produce host antitumor responses is a new approach with a rational basis for treating AIDS-related lymphomas in contrast to conventional chemotherapy regimens.
| Ratner, L; Lee, J; Tang, S et al. (2001) Chemotherapy for human immunodeficiency virus-associated non-Hodgkin's lymphoma in combination with highly active antiretroviral therapy. J Clin Oncol 19:2171-8 |
