Trial Information

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.