Gene Therapy After Frontline Chemotherapy in Treating Patients With AIDS-Related Non-Hodgkin Lymphoma
|ClinicalTrials.gov Identifier: NCT01961063|
Recruitment Status : Active, not recruiting
First Posted : October 11, 2013
Last Update Posted : February 20, 2018
|Condition or disease||Intervention/treatment||Phase|
|AIDS-related Non-Hodgkin Lymphoma AIDS-related Plasmablastic Lymphoma AIDS-related Primary Effusion Lymphoma HIV Infection||Drug: busulfan Biological: lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells Other: pharmacological study Other: laboratory biomarker analysis||Phase 1|
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).
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 (Clinical Trial)|
|Estimated Enrollment :||3 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Safety and Feasibility of Gene Transfer After Frontline Chemotherapy for Non-Hodgkin Lymphoma in AIDS Patients Using Peripheral Blood Stem/Progenitor Cells Treated With a Lentivirus Vector-Encoding Multiple Anti-HIV RNAs|
|Actual Study Start Date :||June 11, 2014|
|Estimated Primary Completion Date :||June 2031|
|Estimated Study Completion Date :||June 2031|
Experimental: Treatment (gene therapy)
Patients receive busulfan IV over 3 hours on day -2 followed by lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells IV on day 0.
Other Names:Biological: lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells
Other Name: lentivirus-transduced hematopoietic progenitor cellsOther: pharmacological study
Correlative studiesOther: laboratory biomarker analysis
- Procedure related toxicity as determined by adverse events (AE) grading scale using the Common Terminology Criteria for Adverse Events (CTCAE) version v4.03 [ Time Frame: Up to 5 years ]Tables will be created to summarize these toxicities and side effects by dose
- 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 [ Time Frame: Up to 5 years ]PCR-based assay on PBMC
- Expression of the RNA transgenes in lineage-specific progeny of the transduced cells assessed by PCR [ Time Frame: Up to 2 years ]PCR-based assay on FACS-sorted cells
- Effect of ATI on HIV markers and CD4 count [ Time Frame: Up to 5 years ]HIV proviral DNA, HIV RNA single copy, and 2-LTR circle DNA from PBMCs
- Pharmacokinetic parameters of busulfan [ 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 ]Cmax, CLsys, Vd, t1/2's, AUC
- Ability to obtain suitable numbers of transduced HSPC for engraftment assessed by FACS [ Time Frame: Up to day -2 (Pre-infusion of the investigational drug) ]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%.
- Feasibility of product manufacturing as evidenced by product release assessed by release assays [ Time Frame: Up to day -2 (Pre-infusion of the investigational drug) ]Release assays
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01961063
|United States, California|
|City of Hope Medical Center|
|Duarte, California, United States, 91010|
|Principal Investigator:||Amrita Krishnan||City of Hope Medical Center|