Gene Therapy in HIV-Positive Patients With Non-Hodgkin's Lymphoma
The purpose of this study is to see if it is safe and effective to use gene therapy to treat non-Hodgkin's lymphoma (NHL) in HIV-positive patients.
Stem cell transplantation is a procedure used to treat NHL. Stem cells are very immature cells that develop to create all of the different types of blood cells. In this study, some of your stem cells will be treated with gene therapy, meaning the cells are treated with a virus that does not cause disease. Some cells will receive a virus that contains ribozymes, enzymes that may help fight HIV. Other cells will be treated with a virus that does not contain ribozymes to see how the virus works alone. Some cells will not be treated at all. Doctors would like to see whether giving patients stem cells with ribozymes can treat NHL and stop HIV from growing at the same time.
Drug: Peripheral blood stem cells
|Study Design:||Endpoint Classification: Safety Study
Primary Purpose: Treatment
|Official Title:||High Dose Chemotherapy and Autologous Peripheral Stem Cell Transplantation for HIV Lymphomas: A Phase IIA Study of Comparative Marking Using a Ribozyme Gene and a Neutral Gene|
In this study, CD34+ cells (stem cells) are transduced with a retroviral vector construct that incorporates multiple ribozymes, a form of RNA with the ability to selectively inhibit gene expression, targeting different sites within the HIV virus. These transduced cells are reinfused into patients as part of a bone marrow transplant procedure for AIDS/lymphoma.
Patients undergoing autologous bone marrow transplantation are entered into this study. A "neutral" retrovirus named "LN" and a retrovirus that contains two ribozyme sequences named "L-TR/Tat-neo" are introduced into the patient's PBPC. The L-TR/Tat-neo retrovirus has been shown in tissue culture experiments to inhibit the replication of HIV. The LN retrovirus serves as an internal control to examine selective advantage of the gene therapy. Patients have a bone marrow sample taken. After an additional round of chemotherapy with their referring physician, patients receive daily injections of G-CSF to aid in the collection of stem cells. Daily stem cell collections are performed. It is anticipated that three to four collections will be required, but as many as six may be necessary. To prepare for the transplantation of stem cells, patients are admitted for a 7-day series of intensive chemotherapy. Following this conditioning, the gene-modified and untreated stem cells are infused back into the patient. The collected cells are divided into three pools. One is set aside without modification, one is modified with the LN control vector, and one is modified with the L-TR/Tat-neo construct. The LN and L-TR/Tat-neo samples are pooled and given to the patient by IV infusion over about 15 minutes. The unmodified cells are then infused over 10 to 15 minutes. Patients remain in the hospital until their blood cells return to adequate levels and they are well enough to be released. Following transplantation, all patients are followed at Months 1, 3, 6, 9, 12, 18, and 24. Because of the experimental nature of gene therapy, patients are followed periodically throughout their lifetimes.