- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02648516
Safety and Efficacy of Allogenic Adoptive Immune Therapy for Immune Reconstitution in Chronic HIV-1 Infected Patients
Safety and Efficacy of Allogenic Adoptive Immune Therapy for Immune Reconstitution Failure in Chronic HIV-1 Infected Patients
Study Overview
Status
Intervention / Treatment
Detailed Description
There is not a consensus definition of immunologic nonresponder individuals. In this study, we described patients whose cluster of differentiation 4(CD4)+ T-cell count remained below 200 cells/ul after 2 years of effective antiviral as immunologic nonresponders, in which viroimmunological dissociation implies a greater risk of AIDS related and non-AIDS-related illnesses. Immune-based therapy such as interleukin (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 Tissue Mesenchymal Stem Cells (UC-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 T-cell growth factor transforming growth factor (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 human leukocyte antigen (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 MNCs 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 96-week follow up.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Fu-Sheng Wang
- Email: fswang302@163.com
Study Contact Backup
- Name: Yan-Mei Jiao
- Email: jiaoyanmei@sina.com
Study Locations
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Beijing
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Beijing, Beijing, China, 100069
- Recruiting
- Beijing 302 Hospital
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Contact:
- Ji-yuan Zhang, PhD
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Contact:
- Yan-mei Jiao, PhD
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Immune non-responders with chronic HIV-1 infection
- Antiretroviral therapy (ART) for at least 24 months prior to study entry and continue within the 24 months after study entry
- 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
- Viral load less than or equal to 50 copies/mL obtained within 12 months prior to study entry
- Certain specified laboratory values obtained within 30 days prior to study entry. More information on this criterion can be found in the study protocol
- Documentation that pre-entry specimen for the primary immune activation endpoint responses has been obtained
- No history of Centers for Disease Control and Prevention (CDC) category C AIDS-related opportunistic infections
- Karnofsky performance score greater than or equal to 70 within 30 days prior to study entry
- Ability and willingness to provide informed consent
Exclusion Criteria:
- Coinfection with other virus, including serum hepatitis C virus RNA positive, or one of followings are positive in anti-hepatitis A virus/anti-HDV/anti-hepatitis delta virus plus alanine aminotransferase (ALT) more than 80 IU/L
- History of combination with other severe diseases including renal, circulatory, respiratory, digestive, endocrine, neural and immunological diseases and tumors
- White blood cell (WBC) <2.5*10E9/L, platlet counts <50*10E9/L, Hb <80g/L, lactate >2 mmol/L
- Allergic constitution
- Pregnancy or lactation
- Accepting other immunomodulatory drugs within 6 months prior screening
- Drug addiction
- Other conditions possibly influencing the trial
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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 2 study visit.
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Participants will receive ART and taken i.v., at a dose of 2-3*10E8 MNCs/kg body at baseline, week 1 and 2.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The changes of CD4 T cell counts
Time Frame: At Baseline and week 1, 2, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96
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marker for host immunity
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At Baseline and week 1, 2, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The changes of HIV-1 DNA
Time Frame: At Baseline and up to week 96
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marker for HIV-1 reservoir
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At Baseline and up to week 96
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The ratio of CD4 and CD8 T cells
Time Frame: At Baseline and week 1, 2, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96
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marker for host immunity
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At Baseline and week 1, 2, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96
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Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: At Baseline and up to week 96
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marker for safety
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At Baseline and up to week 96
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Wang Fu-Sheng, Beijing 302 Hospital
Publications and helpful links
General Publications
- Hutter G. Stem cell transplantation in strategies for curing HIV/AIDS. AIDS Res Ther. 2016 Sep 13;13(1):31. doi: 10.1186/s12981-016-0114-y. eCollection 2016.
- Zhang Z, Fu J, Xu X, Wang S, Xu R, Zhao M, Nie W, Wang X, Zhang J, Li T, Su L, Wang FS. Safety and immunological responses to human mesenchymal stem cell therapy in difficult-to-treat HIV-1-infected patients. AIDS. 2013 May 15;27(8):1283-93. doi: 10.1097/QAD.0b013e32835fab77.
- Corbeau P, Reynes J. Immune reconstitution under antiretroviral therapy: the new challenge in HIV-1 infection. Blood. 2011 May 26;117(21):5582-90. doi: 10.1182/blood-2010-12-322453. Epub 2011 Mar 14.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Slow Virus Diseases
- HIV Infections
- Acquired Immunodeficiency Syndrome
Other Study ID Numbers
- Beijing302-010
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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