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

This study is currently recruiting participants.
Verified September 2016 by Beijing 302 Hospital
Sponsor:
ClinicalTrials.gov Identifier:
NCT02648516
First Posted: January 7, 2016
Last Update Posted: August 29, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Beijing 302 Hospital
  Purpose
Combination antiretroviral therapy (ART) 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 ART, but 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.

Condition Intervention Phase
Human Immunodeficiency Virus Disorder of Immune Reconstitution Combination Product: Conventional plus AAIT Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Allogenic Adoptive Immune Therapy for Immune Reconstitution Failure 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 ]
    marker for host immunity


Secondary Outcome Measures:
  • The ratio of CD4 and CD8 T cells [ Time Frame: At Baseline and week 1, 2, 3, 4, 8, 12, 16, 24, 48 ]
    marker for host immunity

  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: At Baseline and up to week 48 ]
    marker for safety


Other Outcome Measures:
  • th changes of HIV reservoir [ Time Frame: At Baseline and up to week 48 ]
    marker for HIV


Estimated Enrollment: 20
Actual Study Start Date: October 2016
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Conventional plus AAIT
Participants will receive ART plus a dose of allogenic adoptive immune transfusion (3 times of MNCs transfusions) from day 0 through the week 3 study visit.
Combination Product: Conventional plus AAIT
Participants will receive ART and taken i.v., at a dose of 2-3*10E8 MNCs/kg body at baseline, week 1 and 3.
Other Name: Conventional plus allogenic adoptive immune treatment

Detailed Description:

There is not a consensus definition of immunologic nonresponder individuals. In this study, we described patients whose CD4+ T-cell count remained below 200 cells/ul after 2 years of effective antiviral as immunologic nonresponders, in which viroimmunologic dissociation implies a greater risk of AIDS related and non-AIDS-related illnesses. Immune-based therapy such as IL-2 and IL-7 have been shown to increase CD4 T-cell counts but yielded no clinical benefit in a large randomized study. We have reported that umbilical cord-MSC treatment is safe and can significantly decrease systemic immune overactivation and improve immune reconstitution in INR patients. Meanwhile, we did not find that there was a significantly transitory increase in peripheral CD4 T-cell counts within 1-2 weeks since the onset of each MSC infusion. More important, umbilical cord-MSCs were found to be with a potential to produce IL-7 and TGF-β in vitro and in vivo and preferentially expand CD4 T-cell response in the recipients. Therefore, development of novel interventions to reduce immune overactivation/inflammation and enhance immune reconstitution in INRs is a high priority.

Granulocyte colony-stimulating factor (G-CSF)-mobilized donor peripheral blood mononuclear cells (MNCs) are a heterogeneous population of immune cells that have a potential role in immunomodulation and hemopoiesis. Here, we hypothesized that HLA-mismatched MNCs transfusion can be used to comprehensively restore or boost the host holistic immune system for INR patients, to the degree similar as immune responders.

The purpose of this study is to investigate the safety and initial efficacy of allogeneic adoptive immune therapy (AAIT) for INR patients. 20 INR patients received i.v. transfusion one round (3 times) of 2.0-3.0*10E8 cells/kg of MNSs as the treated group. All of them received the conventional treatment for AIDS. The CD4 T cell numbers, HIV reservoir, side effects, symptom improvement, control of opportunistic infections and will be evaluated during the 48-week follow up.

  Eligibility

Information from the National Library of Medicine

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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 200 cells/mm3 continuously and more than 50 cells/mm3 before entry and at screening, obtained within 30 days prior to study entry
  4. Viral load less than or equal to 50 copies/mL obtained within 12 months 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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02648516


Contacts
Contact: Fu-Sheng Wang fswang302@163.com
Contact: Yan-Mei Jiao jiaoyanmei@sina.com

Locations
China, Beijing
Beijing 302 hospital Recruiting
Beijing, Beijing, China, 100069
Contact: Ji-yuan Zhang, PhD         
Contact: Yan-mei Jiao, PhD         
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
First Submitted: September 8, 2015
First Posted: January 7, 2016
Last Update Posted: August 29, 2017
Last Verified: September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Beijing 302 Hospital:
Immune Reconstitution
Allogenic HLA-Mismatched Mononuclear Cells 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