Clinical Trial: Gene-Modified HIV-Protected Stem Cell Transplant in Treating Patients With HIV-Associated Lymphoma

Study Status: Suspended
Recruit Status: Suspended
Study Type: Interventional

Official Title: Autologous Transplantation and Stem Cell-Based Gene Therapy With LVsh5/C46 (CAL-1), a Dual Anti-HIV Lentiviral Vector, for the Treatment of HIV-Associated Lymphoma

Brief Summary: This clinical trial studies gene-modified, human immunodeficiency virus (HIV)-protected stem cell transplant in treating patients with HIV-associated lymphoma. Stem cells, or cells which help form blood, are collected from the patient and stored. They are treated in the laboratory to help protect the immune system from HIV. Chemotherapy is given before transplant to kill lymphoma cells and to make room for new stem cells to grow. Patients then receive the stem cells that were collected from them before chemotherapy and have been genetically modified to replace the stem cells killed by the chemotherapy.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To assess the safety and feasibility of infusing gene-modified, HIV-protected hematopoietic stem/progenitor cells (HSPC) after high-dose chemotherapy for treatment of acquired immune deficiency syndrome (AIDS)-related lymphoma.

II. To observe the change in gene-modified cell levels before and after antiviral treatment interruption.

SECONDARY OBJECTIVES:

I. To evaluate the molecular and clonal composition of gene-modified cells after hematopoietic cell transplant (HCT).

II. To describe time to disease progression, progression-free survival, treatment-related mortality, time to neutrophil and platelet recovery, and incidence of infections.

TERTIARY OBJECTIVES:

I. To evaluate the effect of procedure on HIV-specific immune reconstitution.

II. To observe the effect of HIV infection on the presence of gene-marked cells as determined by deoxyribonucleic (DNA) polymerase chain reaction (PCR).

OUTLINE:

CONDITIONING: Patients undergo high-dose chemotherapy or chemoradiotherapy according to institutional guidelines.

STEM CELL INFUSION: Patients undergo hematopoietic stem cell transplant with LVsh5/C46 (Cal-1) transduced autologous CD34+ hematopoietic stem/progenitor cells (HSPC) on day 0.

Note: Patients continue to receive highly active antiretroviral therapy (HAART) throughout treatment, with a 7-day break for apheresis
Sponsor: Fred Hutchinson Cancer Research Center

Current Primary Outcome:

  • Feasibility of collection of >= 2.1 x 10^6 CD34+ cells/kg for backup cryopreservation and collection of an additional >= 2.5 x 10^6 CD34+ cells/kg for genetic modification [ Time Frame: Up to 15 years ]
  • Feasibility of genetic modification, defined as evidence for gene modified CD34+ cells in the infusion product [ Time Frame: Up to 15 years ]
  • Feasibility of infusion of gene-modified cells, defined as engraftment of >= 1% gene-modified cells at the time of hematopoietic recovery from conditioning (absolute neutrophil count >= 500/mcL, platelets >= 100,000/mcL for three consecutive evaluations) [ Time Frame: Up to 15 years ]
  • Feasibility of stem cell infusion (STI), defined as the ability to achieve engraftment level and maintain CD4 counts and plasma viremia at levels required for STI eligibility [ Time Frame: Up to 15 years ]
  • Incidence of >= grade 3 toxicity related to the infusion of gene-modified cells, defined by Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 15 years ]
  • Incidence of confirmed insertional mutagenesis [ Time Frame: Up to 15 years ]
  • Incidence of development of confirmed replication competent lentivirus [ Time Frame: Up to 15 years ]
  • Integration sites of vector sequences in peripheral blood mononuclear cells [ Time Frame: Up to 15 years ]
    Characterized if clinical symptoms suggest clonal expansion of the HSPC or if molecular assays result in clonal expansion in > 20% of gene-marked cells.

    Original Primary Outcome:

    • Incidence of >= grade 3 toxicity related to the infusion of gene-modified cells, defined by Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 15 years ]
    • Incidence of development of confirmed replication competent lentivirus [ Time Frame: Up to 15 years ]
    • Incidence of confirmed insertional mutagenesis [ Time Frame: Up to 15 years ]
    • Integration sites of vector sequences in peripheral blood mononuclear cells [ Time Frame: Up to 15 years ]
      Characterized if clinical symptoms suggest clonal expansion of the HSC or if molecular assays result in clonal expansion in > 20% of gene-marked cells.
    • Feasibility of collection of >= 2.1 x 10^6 CD34+ cells/kg for backup cryopreservation and collection of an additional >= 2.5 x 10^6 CD34+ cells/kg for genetic modification [ Time Frame: Up to 15 years ]
    • Feasibility of genetic modification, defined as evidence for gene modified CD34+ cells in the infusion product [ Time Frame: Up to 15 years ]
    • Feasibility of infusion of gene-modified cells, defined as engraftment of >= 1% gene-modified cells at the time of hematopoietic recovery from conditioning (absolute neutrophil count >= 500/mcL, platelets >= 100,000/mcL for three consecutive evaluations) [ Time Frame: Up to 15 years ]
    • Feasibility of stem cell infusion (STI), defined as the ability to achieve engraftment level and maintain CD4 counts and plasma viremia at levels required for STI eligibility [ Time Frame: Up to 15 years ]

      Current Secondary Outcome:

      Original Secondary Outcome:

      Information By: Fred Hutchinson Cancer Research Center

      Dates:
      Date Received: February 27, 2015
      Date Started: June 2016
      Date Completion:
      Last Updated: January 9, 2017
      Last Verified: January 2017