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Safety and Efficacy of Allogenic Adoptive Cell Therpy for Immune Reconstitution in Chronic HIV-1 Infected Patients

This study is not yet open for participant recruitment.
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Verified September 2015 by Beijing 302 Hospital
Sponsor:
Information provided by (Responsible Party):
Beijing 302 Hospital
ClinicalTrials.gov Identifier:
NCT02648516
First received: September 8, 2015
Last updated: January 5, 2016
Last verified: September 2015
  Purpose
Chronic HIV-1 infection is generally characterized by progressive CD4+ T cell depletion associated with risk of opportunistic infections. In clinical, about 20% of patients who exhibit stable viral suppression by HAART still fail to achieve sufficient immune reconstitution and often experience an increased risk of opportunistic infections. Granulocyte colony-stimulating factor-mobilized donor peripheral-blood stem cells based on HLA-mismatched allogeneic transplantation have been demonstrated to boost host immunity against tumor and promote hemopoiesis without acute graft-versus-host disease. Thus, it may represent a novel treatment as allogenic adoptive cell therapy (AACT). Here, the investigators propose a hypothesis that AACT can promote hemopoiesis in bone marrow and attenuate immune-mediated inflammation, which subsequently lead to the restoration of CD4 T-cell counts and reconstitution of host immunity in HIV-infected patients.

Condition Intervention Phase
Human Immunodeficiency Virus Disorder of Immune Reconstitution Other: Conventional plus AAC treatment Other: Conventional plus placebo treatment Phase 1 Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Beijing 302 Hospital:

Primary Outcome Measures:
  • The changes of CD4 T cell counts [ Time Frame: At Baseline and week 1, 2, 3, 4, 8, 12, 16, 24, 48 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 40
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)
Arms Assigned Interventions
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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Immune non-responders with chronic HIV-1 infection
  2. Antiretroviral therapy (ART) for at least 24 months prior to study entry and continue within the 24 months after study entry
  3. CD4 count less than or equal to 250 cells/mm3 continuously and more than 50 cells/mm3 before entry and at screening, obtained within 30 days prior to study entry
  4. Vral load less than or equal to 50 copies/mL obtained within 30 days prior to study entry
  5. Certain specified laboratory values obtained within 30 days prior to study entry. More information on this criterion can be found in the study protocol
  6. Documentation that pre-entry specimen for the primary immune activation endpoint responses has been obtained
  7. No history of CDC category C AIDS-related opportunistic infections
  8. Karnofsky performance score greater than or equal to 70 within 30 days prior to study entry
  9. Ability and willingness to provide informed consent

Exclusion Criteria:

  1. Coinfection with other virus, including serum HCV RNA positive, or one of followings are positive in anti-HAV/anti-HDV/anti-HEV plus ALT more than 80 IU/L
  2. History of combination with other severe diseases including renal, circulatory, respiratory, digestive, endocrine, neural and immunological diseases and tumors
  3. WBC <2.5*10E9/L, platlet counts <50*10E9/L, Hb <80g/L, lactate >2 mmol/L
  4. Allergic constitution
  5. Accepting other immunomodulatory drugs within 6 months prior screening
  6. Drug addiction
  7. Other conditions possibly influencing the trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02648516

Contacts
Contact: Fu-Sheng Wang fswang302@163.com
Contact: Ji-Yuan Zhang uniquezjy@163.com

Sponsors and Collaborators
Beijing 302 Hospital
Investigators
Principal Investigator: Wang Fu-Sheng Beijing 302 Hospital
  More Information

Publications:
Responsible Party: Beijing 302 Hospital
ClinicalTrials.gov Identifier: NCT02648516     History of Changes
Other Study ID Numbers: Beijing302-010
Study First Received: September 8, 2015
Last Updated: January 5, 2016
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by Beijing 302 Hospital:
Immune Reconstitution
Allogenic HLA-Mismatched Stem-Cell Transplantation

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on June 26, 2017