Gene Therapy-Treated Stem Cells in Treating Patients Undergoing Stem Cell Transplant for Intermediate-Grade or High-Grade AIDS-Related Lymphoma

Lymphoma Clinical Trial

Official title: A Pilot Study of Safety and Feasibility of Stem Cell Therapy for Aids Lymphoma Using Stem Cells Treated With a Lentivirus Vector-Encoding Multiple Anti-HIV RNAs

Status Completed

Clinical Trial Summary

This pilot clinical trial studies biological therapy in treating patients with acquired immune deficiency syndrome (AIDS)-related lymphoma undergoing stem cell transplant. Giving chemotherapy before a stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and stored. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Giving biological therapy as part of the stem cell transplant may be more effective in treating patients with AIDS-related lymphoma

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the safety and feasibility of using lentivirus-transduced hematopoietic progenitor cells (HPCs) (lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells) in the setting of autologous hematopoietic cell transplantation (HCT) for treatment of AIDS related lymphoma. The safety of the of the genetically modified product used in the transplant procedure will be assessed by monitoring each subject for adverse events (procedure related toxicity); absolute neutrophil count (ANC)/platelet engraftment (sustained recovery); and evidence of replication competent vector or vector recombination with the human immunodeficiency virus (HIV) quasi-species present in the patient.

II. To determine the quantity and duration of vector-marked peripheral blood cells and to characterize: the duration and level of gene marking and expression of the anti-HIV ribonucleic acids (RNAs) in these transduced cells, and the characterization of the integration sites of vector sequences in circulating cells if there is a clinical syndrome suggestive of a clonal expansion of hematopoietic cells. In addition, the feasibility of the process will be assessed based on the results of the release testing of the transduced cells prior to injection into the patient.

III. To determine whether the design of the vector prevents vector mobilization and rescue by wild-type HIV-1. IV. To measure the effect of HIV infection on the presence of HIV-resistant blood cells as measured by genetic marking for vector sequences before and after antiviral treatment interruption.

OUTLINE:

CONDITIONING: Patients receive carmustine intravenously (IV) over 1-2 hours on days -7 to -5, etoposide IV over 4 hours on day -4, and cyclophosphamide IV on day -2.

TRANSPLANTATION: Patients undergo autologous hematopoietic stem cell transplantation comprising lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells and non-bound cluster of differentiation (CD)34+ cells IV on day 0. After completion of study treatment, patients are followed up every 2 weeks for 3 months; at 4, 6, 8, 10, 12, 18, and 24 months; every 6 months for 3 years; and then annually for 10 years. ;

Related Conditions & MeSH terms

• Lymphoma

• NCT number: NCT00569985
• Study type: Interventional
• Source: City of Hope Medical Center
• Status: Completed
• Phase: Phase 1
• Start date: June 2007
• Completion date: November 12, 2019