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Ensayos clínicos

Ensayos clínicos

Gene Therapy in HIV-Positive Patients with Non-Hodgkin's Lymphoma

Patrocinador(es) del estudio: Ribozyome
Números de identificación: NCT00002221, STUDY 2
  • Concluido

Propósito del estudio

To assess the safety and feasibility of administering peripheral blood progenitor cells (PBPC) transduced with retroviral vectors encoding an anti-HIV double ribozyme to HIV-infected patients undergoing intensive chemotherapy and stem cell transplantation for non-Hodgkin's lymphoma (NHL). To determine whether these genetically modified PBPC can engraft, differentiate, and circulate in the blood of transplanted recipients. To determine the comparative survival of ribozyme-vector transduced PBPC versus control vector marked cells in the periphery. To evaluate the toxicity and disease-free survival associated with high-dose chemotherapy with stem cell transplantation in HIV-infected patients with NHL.

Afección:Fase:
Linfoma No Hodgkin
Infecciones por el VIH
Fase 2

Detalles del estudio

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.

Criterios de exclusión

    You will not be eligible for this study if you: Have lymphoma affecting your nervous system. Have had any AIDS-related opportunistic infections in the past year. Have heart disease. Are pregnant or breast-feeding. Have severe diarrhea. Have a history of cytomegalovirus (CMV) retinitis. Have dementia or encephalopathy (an infection of the brain). Have a history of another type of cancer (except for skin cancer) before your diagnosis of NHL. Are allergic to etoposide or have had a toxic reaction to prior chemotherapy.

Centros de estudio/contactos

California

    City of Hope Natl Med Ctr, Duarte, California, 91010, United States

Actualizado: 24 de junio del 2003

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