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
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.
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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety of treatment using the National Cancer Institute (NCI) hematologic Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
The toxicities observed after each stem cell infusion will be summarized in terms of type (organ affected or laboratory determination such as ANC), severity (by NCI CTCAE version 3 and nadir or maximum values for the laboratory measures), time of onset (i.e., course number), duration, and reversibility of outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.
15 years post stem cell infusion
Amrita Y. Krishnan, MD
City of Hope Medical Center
United States: Food and Drug Administration
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