NCT02337985

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

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

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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 description

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.

Conditions

• 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

Interventions

Type	Name	Description
DRUG	Prednisone	Given PO
BIOLOGICAL	Rituximab	Given IV
DRUG	Etoposide	Given IV
DRUG	Doxorubicin Hydrochloride	Given IV
DRUG	Vincristine Sulfate	Given IV
DRUG	Cyclophosphamide	Given IV
BIOLOGICAL	Filgrastim	Given SC
BIOLOGICAL	Lentivirus Vector rHIV7-shI-TAR-CCR5RZ-transduced Hematopoietic Stem/Progenitor Cells	Given IV

Timeline

• Start date: 2015-11-20
• Primary completion: 2026-09-08
• Completion: 2026-09-08
• First posted: 2015-01-14
• Last updated: 2025-11-10

Locations

1 site across 1 country: United States