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AUTOLOGOUS TRANSPLANTATION AND STEM CELL BASED-GENE THERAPY FOR THE TREATMENT OF HIV-ASSOCIATED LYMPHOMA
This clinical trial studies genetically modified peripheral blood stem cell transplant in treating patients with HIV-associated non-Hodgkin or Hodgkin lymphoma. Giving chemotherapy before a peripheral 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. More chemotherapy or radiation therapy is then given to prepare the bone marrow for the stem cell transplant. Laboratory-treated stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy
PRIMARY OBJECTIVES: 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 interruption. SECONDARY OBJECTIVES: 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. TERTIARY OBJECTIVES: I. Effect of procedure on the latent HIV reservoir. II. Effect of procedure on HIV-specific immune reconstitution. OUTLINE: 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.
Age
18 - 66 years
Sex
ALL
Healthy Volunteers
No
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States
Start Date
February 1, 2015
Primary Completion Date
February 1, 2019
Last Updated
May 7, 2015
carmustine
DRUG
cytarabine
DRUG
melphalan
DRUG
etoposide
DRUG
O6-benzylguanine
DRUG
autologous hematopoietic stem cell transplantation
PROCEDURE
peripheral blood stem cell transplantation
PROCEDURE
laboratory biomarker analysis
OTHER
Lead Sponsor
Fred Hutchinson Cancer Center
Collaborators
NCT03493451
NCT02168140
Data Source & Attribution
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