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.
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). After completion of study treatment, patients are followed up at 1, 2, 3, 6, 9, 12, 18, and 24 months, every 6 months for 3 years, and then annually for 10 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Given PO
Given IV
Given IV
Given IV
Given IV
Given IV
Given SC
NCI Lymphoid Malignancies Branch
Bethesda, Maryland, United States
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
Tables will be created to summarize these toxicities and side effects by dose and by course.
Time frame: Up to 2 years after completion of treatment
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
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.
Time frame: Up to 2 years
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
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
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.
Time frame: Up to 15 years
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
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