Gene Therapy in HIV-Positive Patients With Non-Hodgkin's Lymphoma
Condition: Lymphoma, Non-Hodgkin; HIV Infections
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to see if it is safe and effective to use gene therapy to treat
      non-Hodgkin's lymphoma (NHL) in HIV-positive patients.

      Stem cell transplantation is a procedure used to treat NHL. Stem cells are very immature
      cells that develop to create all of the different types of blood cells. In this study, some
      of your stem cells will be treated with gene therapy, meaning the cells are treated with a
      virus that does not cause disease. Some cells will receive a virus that contains ribozymes,
      enzymes that may help fight HIV. Other cells will be treated with a virus that does not
      contain ribozymes to see how the virus works alone. Some cells will not be treated at all.
      Doctors would like to see whether giving patients stem cells with ribozymes can treat NHL and
      stop HIV from growing at the same time.
    

Detailed description: 
      In this study, CD34+ cells (stem cells) are transduced with a retroviral vector construct
      that incorporates multiple ribozymes, a form of RNA with the ability to selectively inhibit
      gene expression, targeting different sites within the HIV virus. These transduced cells are
      reinfused into patients as part of a bone marrow transplant procedure for AIDS/lymphoma.

      Patients undergoing autologous bone marrow transplantation are entered into this study. A
      "neutral" retrovirus named "LN" and a retrovirus that contains two ribozyme sequences named
      "L-TR/Tat-neo" are introduced into the patient's PBPC. The L-TR/Tat-neo retrovirus has been
      shown in tissue culture experiments to inhibit the replication of HIV. The LN retrovirus
      serves as an internal control to examine selective advantage of the gene therapy. Patients
      have a bone marrow sample taken. After an additional round of chemotherapy with their
      referring physician, patients receive daily injections of G-CSF to aid in the collection of
      stem cells. Daily stem cell collections are performed. It is anticipated that three to four
      collections will be required, but as many as six may be necessary. To prepare for the
      transplantation of stem cells, patients are admitted for a 7-day series of intensive
      chemotherapy. Following this conditioning, the gene-modified and untreated stem cells are
      infused back into the patient. The collected cells are divided into three pools. One is set
      aside without modification, one is modified with the LN control vector, and one is modified
      with the L-TR/Tat-neo construct. The LN and L-TR/Tat-neo samples are pooled and given to the
      patient by IV infusion over about 15 minutes. The unmodified cells are then infused over 10
      to 15 minutes. Patients remain in the hospital until their blood cells return to adequate
      levels and they are well enough to be released. Following transplantation, all patients are
      followed at Months 1, 3, 6, 9, 12, 18, and 24. Because of the experimental nature of gene
      therapy, patients are followed periodically throughout their lifetimes.
    

Intervention name(s): Peripheral blood stem cells
Intervention type(s): Drug
Primary purpose: Treatment
Keywords: Lymphoma, Non-Hodgkin; Bone Marrow; Lymphocyte Transformation; HIV-1; Retroviridae; Lymphoma, AIDS-Related; Genetic Vectors; Transduction, Genetic; Gene Transfer Techniques