Gene Therapy-Treated Stem Cells in Treating Patients Undergoing Stem Cell Transplant for Intermediate-Grade or High-Grade AIDS-Related Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma
Study type: Interventional
Phase: Phase 1

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 description: 
      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 -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.
    

Intervention name(s): lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells; carmustine; cyclophosphamide; etoposide; autologous hematopoietic stem cell transplantation
Intervention type(s): Biological; Drug; Drug; Drug; Procedure
Intervention description(s): Undergo autologous hematopoietic stem cell transplantation comprising lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells and non-bound CD34+ cells; Given IV; Given IV; Given IV; Undergo autologous hematopoietic stem cell transplantation comprising lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells and non-bound CD34+ cells
Other intervention name(s): lentivirus-transduced hematopoietic progenitor cells; BCNU; BiCNU; bis-chloronitrosourea; CPM; CTX; Cytoxan; Endoxan; Endoxana; EPEG; VP-16; VP-16-213
Intervention MeSH terms: Cyclophosphamide; Carmustine; Etoposide; Etoposide phosphate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: AIDS-related diffuse large cell lymphoma; AIDS-related diffuse mixed cell lymphoma; AIDS-related diffuse small cleaved cell lymphoma; AIDS-related immunoblastic large cell lymphoma; AIDS-related small noncleaved cell lymphoma; HIV-associated Hodgkin lymphoma; Treatment Experienced