This pilot clinical trial studies gene therapy after frontline chemotherapy in treating patients with acquired immune deficiency syndrome (AIDS)-related non-Hodgkin lymphoma (NHL). Placing genes for anti-human immunodeficiency virus (HIV) ribonucleic acid (RNA) into stem/progenitor cells may make the body build an immune response to AIDS. Giving the chemotherapy drug busulfan before gene therapy can help gene-modified cells engraft and work better.
PRIMARY OBJECTIVES: I. To evaluate the safety and feasibility of recombinant (r)HIV7-short hairpin RNA targeted to the HIV-1 tat/rev (shI)-trans-active response element (TAR)-chemokine cysteine-cysteine receptor 5 ribozyme (CCR5RZ)-treated hematopoietic stem progenitor cells (HSPC) (lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells) infusion in AIDS patients completing treatment for NHL and non-myeloablative conditioning with busulfan. 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). SECONDARY OBJECTIVES: I. To evaluate the pharmacokinetics of busulfan in patients with AIDS-related lymphoma (ARL). II. To determine the effects of HIV-1 infection on the presence of gene-marked peripheral blood mononuclear cells (PBMC) as measured by woodchuck post-transcriptional regulatory element (WPRE) deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) performed before, during, and after ATI. OUTLINE: Patients receive busulfan intravenously (IV) over 3 hours on day -2 followed by lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells IV on day 0. After completion of study treatment, patients are followed up at 1, 7, 14, and 21 days and 1, 2, 3, 6, 9, 12, 18, and 24 months and then annually for 3 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
3
City of Hope Medical Center
Duarte, California, United States
Procedure related toxicity as determined by adverse events (AE) grading scale using the Common Terminology Criteria for Adverse Events (CTCAE) version v4.03
Tables will be created to summarize these toxicities and side effects by dose
Time frame: Up to 5 years
Time to Absolute Neutrophil Count (ANC) >= 500/uL
Time frame: First 28 days
Time to platelet recovery to >= 50,000/uL
Time frame: First 90 days
Evidence for and duration of vector-marked PBMC/marrow cells assessed by PCR
PCR-based assay on PBMC
Time frame: Up to 5 years
Expression of the RNA transgenes in lineage-specific progeny of the transduced cells assessed by PCR
PCR-based assay on FACS-sorted cells
Time frame: Up to 2 years
Effect of ATI on HIV markers and CD4 count
HIV proviral DNA, HIV RNA single copy, and 2-LTR circle DNA from PBMCs
Time frame: Up to 5 years
Pharmacokinetic parameters of busulfan
Cmax, CLsys, Vd, t1/2's, AUC
Time frame: Day -2 at 0 hours (pre-infusion); 3 hours (just before end of infusion); and at 4, 5, and 6 hours and day -1 at 24 hours
Ability to obtain suitable numbers of transduced HSPC for engraftment assessed by FACS
The number and type of cells will be determined by fluorescence activated cell sorting (FACS) analysis of the final cell product. The minimum target number of CD34+ cells for collection is 7.5 x 10e6 cells/kg and, in the final transduced cell product, the number of CD34+ cells must be \>= 2.0 x 10e6 CD34+ cells/kg with total viability \>= 70%.
Time frame: Up to day -2 (Pre-infusion of the investigational drug)
Feasibility of product manufacturing as evidenced by product release assessed by release assays
Release assays
Time frame: Up to day -2 (Pre-infusion of the investigational drug)
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