Safety and Efficacy of Allogenic Adoptive Immune Therpy for Immune Reconstitution in Chronic HIV-1 Infected Patients
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|ClinicalTrials.gov Identifier: NCT02648516|
Recruitment Status : Unknown
Verified September 2016 by Beijing 302 Hospital.
Recruitment status was: Recruiting
First Posted : January 7, 2016
Last Update Posted : August 29, 2017
|Condition or disease||Intervention/treatment||Phase|
|Human Immunodeficiency Virus Disorder of Immune Reconstitution||Combination Product: Conventional plus AAIT||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Safety and Efficacy of Allogenic Adoptive Immune Therapy for Immune Reconstitution Failure in Chronic HIV-1 Infected Patients|
|Actual Study Start Date :||October 2016|
|Estimated Primary Completion Date :||July 2018|
|Estimated Study Completion Date :||December 2018|
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
- 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
- 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
- th changes of HIV reservoir [ Time Frame: At Baseline and up to week 48 ]marker for HIV
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
|Beijing 302 hospital||Recruiting|
|Beijing, Beijing, China, 100069|
|Contact: Ji-yuan Zhang, PhD|
|Contact: Yan-mei Jiao, PhD|
|Principal Investigator:||Wang Fu-Sheng||Beijing 302 Hospital|