Safety and Efficacy of Allogenic Adoptive Cell Therpy for Immune Reconstitution in Chronic HIV-1 Infected Patients
|Human Immunodeficiency Virus Disorder of Immune Reconstitution||Other: Conventional plus AAC treatment Other: Conventional plus placebo treatment||Phase 1 Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Participant)
Primary Purpose: Treatment
|Official Title:||Safety and Efficacy of Allogenic Adoptive Cell Therapy for Immune Reconstitution in Chronic HIV-1 Infected Patients|
- The changes of CD4 T cell counts [ Time Frame: At Baseline and week 1, 2, 3, 4, 8, 12, 16, 24, 48 ]
- The plasma RNA copies/mL [ Time Frame: At Baseline and week 4, 12, 24, 48 ]
- The ratio of CD4 and CD8 T cells [ Time Frame: At Baseline and at day 3,4 and week 1, 2, 3, 4, 8, 12, 16, 24, 48 ]
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: At Baseline and up to week 48 ]
|Study Start Date:||April 2016|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||April 2017 (Final data collection date for primary outcome measure)|
Experimental: Conventional plus AAC treatment
Participants will receive conventional treatment plus a dose of allogenic adoptive cell transfusions from Day 0 through the Week 3 study visit. Participants will then be followed until the Week 24 or Week 48 study visit.
Other: Conventional plus AAC treatment
Participants received conventional treatment and taken i.v., at a dose of 2-3*10E8 allogenic adoptive cells/kg body at baseline, week 1 and 3.
Other Name: Conventional plus allogenic adoptive cell treatment
Experimental: Conventional plus placebo treatment
Participants will receive conventional plus placebo treatment from Day 0 through the Week 3 study visit. Participants will then be followed until the Week 24 or Week 48 study visit.
Other: Conventional plus placebo treatment
Participants received conventional treatment and taken i.v., at 50 ml saline at baseline, week 1 and 3.
Chronic HIV-1 infection is generally characterized by progressive CD4 T-cell depletion associated with increased immune activation and risk of opportunistic infections. HAART effectively suppresses viral replication, leading to a significant immune recovery and a dramatic reduction in the incidence of AIDS-defining events. However, approximately 20% of individuals who exhibit stable viral suppression by HAART still fail to achieve sufficient immune reconstitution and are considered immune nonresponders (INRs). These INRs often experience an increased risk of opportunistic infections and shorter life expectancy compared with matched immune responders.Therefore, efficiently treating these immune nonresponders has become one of the most difficult challenges in the clinic.
Granulocyte colony-stimulating factor (G-CSF)-mobilized donor peripheral-blood stem cells (GPBSCs) are a heterogeneous population of immune cells that have a potential role in immunomodulation and hemopoiesis. GPBSCs based on HLA-mismatched allogeneic transplantation have recently emerged as promising candidates for cell-based immunotherapy. Infusion of GPBSCs has been demonstrated to boost host immunity against tumor and promote hemopoiesis in a cohort of patients with acute myeloid leukemia. It represent a novel treatment as allogenic adoptive cell therapy (AACT) and has several characters as below: Before transplantation, donor and recipient HLA-A, -B, -C, -DRB1, and -DQB1 loci were typed at intermediate resolution by a polymerase chain reaction with sequence-specific primer method. All AACT-treated INR patients had related donors who were HLA mismatched. Donors who had more matched HLA loci and matched red blood cell (RBC) type were first chosen. However, donor sex, age, and other characteristics were not considered with priority.The donor was subcutaneously injected with 5μg/kg G-CSF twice a day for 5 days and then peripheral mononuclear cells was carried out with a CS-3000S cell separator. Donor cells were divided into aliquots and were cryopreserved in liquid nitrogen, but freshly collected cells were used in the first course.
The purpose of this study is to investigate the safety and initial efficacy of AACT for INR patients. 20 INR patients received i.v. transfusion of 2.0-3.0*10E8 cells/kg of GPBSCs as the treated group and other 20 INR patients were transfused with placebo without GPBSCs as control group.
All 40 of them received the routine management for AIDS. During the 24- or 48-week follow up, the evaluation of safety and efficacy will be undergone to help to establish innovative cell-based therapies for the treatment of diseases.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02648516
|Principal Investigator:||Wang Fu-Sheng||Beijing 302 Hospital|