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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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

Brief 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

Detailed Summary:

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
Sponsor: City of Hope Medical Center

Current Primary Outcome:

  • Safety of treatment using the National Cancer Institute (NCI) hematologic Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: 15 years post stem cell infusion ]
    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.
  • Survival of shI-TAR-CCR5RZ-marked cells in the peripheral blood, demonstrated by presence of transgene by Q-PCR using primers specific for rHIV7-shI-TAR-CCR5RZ in serial samples of peripheral blood [ Time Frame: 24 months post stem cell infusion ]
  • Determination of RNA transgene expression in samples of peripheral blood mononuclear cells (PBMCs) or marrow before and after infusion, analyzed by Northern blotting/hybridization [ Time Frame: Day 1 post stem cell infusion ]
    For detection of the shRNA, we will use a quantitative real-time PCR assay.
  • Analysis of vector rescue by HIV [ Time Frame: 15 years post stem cell infusion ]
    Integration analysis will be performed only if there is a clinical syndrome that suggests clonal expansion of hematopoietic cells. In that situation, the method of insertion site location will use a linear amplification mediated (LAM)-PCR technique. If positive vector sequences are found in the plasma, confirmation of vector rescue will be done by isolation of HIV an

    Original Primary Outcome:

    • Safety
    • Feasibility


    Current Secondary Outcome:

    Original Secondary Outcome:

    Information By: City of Hope Medical Center

    Dates:
    Date Received: December 7, 2007
    Date Started: June 2007
    Date Completion: July 2017
    Last Updated: February 17, 2017
    Last Verified: February 2017