Gene Therapy and Combination Chemotherapy in Treating Patients With AIDS-Related Non-Hodgkin Lymphoma
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|ClinicalTrials.gov Identifier: NCT02337985|
Recruitment Status : Recruiting
First Posted : January 14, 2015
Last Update Posted : February 20, 2018
|Condition or disease||Intervention/treatment||Phase|
|AIDS-Related Burkitt Lymphoma AIDS-Related Diffuse Large B-cell Lymphoma AIDS-Related Plasmablastic Lymphoma AIDS-Related Primary Effusion Lymphoma HIV Infection AIDS Related Non-Hodgkin Lymphoma||Drug: Prednisone Biological: Rituximab Drug: Etoposide Drug: Doxorubicin Hydrochloride Drug: Vincristine Sulfate Drug: Cyclophosphamide Biological: Filgrastim Biological: Lentivirus Vector rHIV7-shI-TAR-CCR5RZ-transduced Hematopoietic Stem/Progenitor Cells||Phase 1|
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).
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).
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 (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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 Multiple Anti-HIV RNAs|
|Actual Study Start Date :||August 3, 2015|
|Estimated Primary Completion Date :||March 2018|
|Estimated Study Completion Date :||March 2018|
Experimental: Treatment (R-EPOCH, rHIV7-shI-TAR-CCR5RZ-transduced HSPC)
Patients receive prednisone PO BID on days 1-5; rituximab IV on day 1; etoposide IV over 96 hours, doxorubicin hydrochloride IV over 96 hours 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 SC 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.)
Given POBiological: Rituximab
Other Name: MOAB IDEC-C2B8Drug: Etoposide
Other Names:Drug: Doxorubicin Hydrochloride
Other Name: AdriamycinDrug: Vincristine Sulfate
Other Names:Drug: Cyclophosphamide
Given IVBiological: Filgrastim
Other Names:Biological: Lentivirus Vector rHIV7-shI-TAR-CCR5RZ-transduced Hematopoietic Stem/Progenitor Cells
Other Name: lentivirus-transduced hematopoietic progenitor cells
- 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 ]
- 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 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02337985
|United States, Maryland|
|NCI Lymphoid Malignancies Branch||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: Mark J. Roschewski, MD 301-451-9021 firstname.lastname@example.org|
|Contact: Margaret Shovlin, RN 240-760-6089 email@example.com|
|Principal Investigator: Mark J. Roschewski, MD|
|Principal Investigator:||Amrita Krishnan, MD||City of Hope Medical Center|
|Principal Investigator:||Mark J. Roschewski, MD||NCI Lymphoid Malignancy Branch|