Clinical Trial: Gene Therapy and Combination Chemotherapy in Treating Patients With AIDS-Related Non-Hodgkin Lymphoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Safety and Feasibility of Stem Cell Gene Transfer Following R-EPOCH for Non-Hodgkin Lymphoma in AIDS Patients Using Peripheral Blood Stem/Progenitor Cells Treated With a Lentivirus Vector-Encoding Mul

Brief Summary: This pilot clinical trial studies gene therapy following combination chemotherapy in treating patients with acquired immune deficiency syndrome (AIDS)-related non-Hodgkin lymphoma. Placing genes that have been shown in the laboratory to inhibit the growth and spread of the immunodeficiency virus (HIV) into the patient's peripheral blood stem cells may improve the body's ability to fight HIV. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving gene therapy after combination chemotherapy may improve the body's ability to fight HIV and AIDS-related non-Hodgkin lymphoma.

Detailed Summary:

PRIMARY OBJECTIVE:

I. To demonstrate the safety and feasibility of rHIV7-shI-TAR-CCR5RZ-treated hematopoietic stem progenitor cells (HSPC) (lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells) transplantation in AIDS patients completing treatment for non-Hodgkin lymphoma (NHL).

SECONDARY OBJECTIVES:

I. To determine the effect of HIV infection on the presence of gene-marked blood cells as measured by woodchuck post-transcriptional regulatory element (WPRE) deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) performed before, during, and after ATI.

II. To demonstrate the engraftment of gene-modified progeny cells following such treatment.

III. To determine if selection of these gene-modified progeny cells occurs during analytical treatment interruption (ATI) of combination anti-retroviral therapy (cART).

OUTLINE:

Patients receive prednisone orally (PO) twice daily (BID) on days 1-5; rituximab intravenously (IV) on day 1; etoposide, doxorubicin hydrochloride and vincristine sulfate IV over 96 hours on days 1-4; and cyclophosphamide IV over 30-60 minutes on day 5. Patients then receive filgrastim subcutaneously (SC) once daily (QD) beginning on day 6 and continuing until absolute neutrophil count recovers. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients then receive lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic stem/progenitor cells IV on day 0 (48 hours after the final combination chemotherapy course).

Current Primary Outcome:

• Incidence of adverse events related to R-EPOCH, graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 [ Time Frame: Up to 2 years after completion of treatment ]
  Tables will be created to summarize these toxicities and side effects by dose and by course.
• Incidence of adverse events related to lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic stem/progenitor cells infusion, graded using the NCI CTCAE version 4.03 [ Time Frame: Up to 2 years ]
  All toxicities, related and unrelated, observed after each stem cell infusion will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI CTCAE and nadir or maximum values for the laboratory measures), time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.
• Ability to obtain suitable numbers of lentiviral vector treated HSPC as determined by cell count [ Time Frame: Up to day -2 (pre-infusion) ]
• Presence of transgene in peripheral blood by digital droplet PCR [ Time Frame: Up to 2 years ]

Original Primary Outcome:

• Incidence of adverse events related to R-EPOCH, graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 2 years after completion of treatment ]
  Tables will be created to summarize these toxicities and side effects by dose and by course.
• Incidence of adverse events related to lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic stem/progenitor cells infusion, graded using the NCI CTCAE version 4.0 [ Time Frame: Up to 2 years ]
  All toxicities, related and unrelated, observed after each stem cell infusion will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI CTCAE and nadir or maximum values for the laboratory measures), time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.
• Ability to obtain suitable numbers of lentiviral vector treated HSPC as determined by cell count [ Time Frame: Up to day -2 (pre-infusion) ]
• Presence of transgene in peripheral blood by quantitative PCR (TaqMAn analysis) [ Time Frame: Up to 2 years ]

Current Secondary Outcome:

• Transgene ribonucleic acid expression by Northern blotting/hybridization and quantitative real-time PCR assay [ Time Frame: Up to 15 years ]
• HIV reservoir as determined by HIV-1 reverse transcriptase (RT)-PCR, DNA PCR, and DNA 2 long terminal repeat circle PCR [ Time Frame: Up to 15 years and during ATI ]
• HIV integration analysis by number of reads and loci [ Time Frame: Up to 15 years ]
  Integration analyses will be done at month 6 and 12, and at week 16 of ATI, and at times when there is a clinical syndrome that suggests clonal expansion of hematopoietic cells.
• Vector transgene sequences in peripheral blood mononuclear cells [ Time Frame: Up to 2 years, possibly up to 15 years ]
• Change in of shI-TAR-CCR5RZ-marked cells in bone marrow [ Time Frame: Baseline to up to 18 months ]

Original Secondary Outcome: Same as current

Information By: City of Hope Medical Center

Dates:
Date Received: December 23, 2014
Date Started: August 3, 2015
Date Completion: March 2018
Last Updated: May 1, 2017
Last Verified: May 2017