AUTOLOGOUS TRANSPLANTATION AND STEM CELL BASED-GENE THERAPY FOR THE TREATMENT OF HIV-ASSOCIATED LYMPHOMA
I. To determine the safety and feasibility of infusing gene-modified, human immunodeficiency
virus (HIV)-protected hematopoietic stem cells (HSC) after high-dose chemotherapy for
treatment of acquired immunodeficiency syndrome (AIDS)-related lymphoma.
II. To determine the dose of carmustine (BCNU) in combination with O^6-benzylguanine (O6BG)
that results in selection in vivo of gene-modified HIV-resistant cells.
III. To estimate 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
I. Evaluate the molecular and clonal composition of gene-modified cells after hematopoietic
cell transplant (HCT).
II. Evaluate the molecular and clonal composition of gene-modified cells after O6BG/BCNU.
III. Determine the correlation of the level of O6-methylguanine- methyltransferase (MGMT)
(P140K) marking with toxicity and response.
IV. Characterize the toxicity associated with in vivo selection. V. Determine the efficacy
of the procedure for treatment of lymphoma: defined as time to disease progression,
progression-free survival, treatment-related mortality, time to neutrophil and platelet
recovery, and incidence of infections.
I. Effect of procedure on the latent HIV reservoir. II. Effect of procedure on HIV-specific
CONDITIONING: Patients receive carmustine intravenously (IV) over 3 hours on day -7,
cytarabine IV over 2 hours twice daily (BID) and etoposide IV over 2 hours BID on days -6 to
-3, and melphalan IV over 30 minutes on day -2.
TRANSPLANTATION: Patients receive an autologous PBSC infusion and/or infusion of autologous
transduced hematopoietic cells on day 0.
Beginning 28-120 days later, patients eligible for in vivo selection after detection of
gene-marked cells receive O6-benzylguanine IV over 1 hour and carmustine IV over 3 hours on
days 14, 28, and then monthly until completion of therapy. Patients achieving > 10% gene
marking and CD4 count of >= 500 cells/uL receive up to 2 courses of structured treatment
interruption without undergoing in vivo selection.
After completion of study treatment, patients are followed up periodically for 15 years.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety of infusion of gene-modified cells, measured by grade 3 or greater toxicities related to infusion of gene-modified cells using the Common Toxicity Criteria version 4.0(CTCv.4)
Up to day 180
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Federal Government
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