Allogeneic Adoptive Immune Therapy for Advanced AIDS Patients

Safety and Efficiency of Allogeneic Adoptive Immune Therapy for Advanced AIDS Patients

Combined antiretroviral therapy (ART) efficiently suppresses viral replication and markedly decreases mortality among patients with HIV-1 infection/AIDS. While the advanced AIDS patients with CD4+T cell count less than 200 cells/µL often develop seriously opportunistic infections (OIs), severe wasting syndrome, and other fatal complications, which are the major causes of death in these patients. There has been no effective immune therapy for advanced AIDS patients who had a high mortality rate even in the era of cART. This clinical trail is to inspect the efficiency of allogeneic adoptive immune therapy for advanced AIDS patients.

Study Overview

• Status: Recruiting
• Conditions: AIDS Patients
• Intervention / Treatment: Biological: Allogeneic Adoptive Immune Therapy

Detailed Description

Combined antiretroviral therapy (ART) efficiently suppress viral replication and dramatically decrease mortality of the disease in HIV-1/AIDS patients.1 While in cART naive patients with chronic human immunodeficiency virus-1 (HIV-1) infection often characterized by HIV-1 replication, immune activation and deficiency, which lead to profound and systematic inflammation and pathoglogical change, especially in the AIDS patients with CD4 T count less than 50/uL, who often develop deadly complications, which accounts for the major cause of death group in spite of cART era. Up-to-date, there are no effective immune interventions to restore host holistic immunity for advanced AIDS patients.

In pre-cARTera, HLA-matched lymphocytes or stem cell transplantation had been exploratively used in AIDS patients. However, this kind of therapy failed for immunological reconstitution due to the lack of antiviral therapy to suppress HIV-1 replication at that time. With the advent of cART, allogeneic HLA-matched or mismatched lymphocytes or stem cell transplantations were mainly used for AIDS patients with hematopoietic malignancies, the Berlin and London patients were the cured pateints. However, allogeneic transplantation can not be used outside the setting of hematopoietic malignancies. In addition, the high frequency of GVHD (Graft-versus-host disease) owning to a transient or long-lasting engraftment is inevitable.

Until now, there has been no report of effective immune therapy for late-stage AIDS patients with acquired immunodeficiency and severe opportunistic infections (OIs). The urgent challenge is how to efficiently restore the host holistic immunity in AIDS patients at late stage.

The investigators have recently developed a mismatched allogeneic adoptive immune therapy (AAIT) protocol in combination with cART, and found that the treatment was safety and tolerability in a phase I study. The purpose of this study is to further investigate the efficacy of allogeneic adoptive immune therapy (AAIT) for advanced AIDS patients. 120 patients received i.v. transfusion one round (2-3 times) of 1.0-3.0*10E8 cells/kg of MNSs as the treated group, all of these patients received the conventional cART treatment. In addition, the equal 120 patients received cART were used as control. The side effects, CD4 T cell numbers, HIV viral load, clinical symptoms improvement, control of opportunistic infections, AIDS-related events and non-AIDS related events will be evaluated during the 96-week follow up.

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ruonan Xu, MD; Phone Number: 86-10-66933333; Email: xuruonan2004@aliyun.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100039
      • Recruiting
      • Beijing 302 Hospital of China
      • Contact: Fu-Sheng Wang, MD; Phone Number: 01066933328; Email: fswang302@163.com
      • Principal Investigator: Fu-Sheng Wang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female, aged at 18 years (including) -65 years old
2. Advanced AIDS patients with AIDS-related events
3. Advanced patients with CD4 count less than or equal to 200 cells/uL, including end-stage patients with CD4 count less than or equal to 50 cells/uL before entry and at screening
4. Sign informed consent, do not participate in other clinical trails during the period

Exclusion Criteria:

1. Pregnancy, lactation and those who are not pregnant but do not take effective contraceptives measures
2. Combined with other serious organic diseases while didn't related with AIDS
3. HIV-2 infection
4. Allergic to blood products
5. Under long term immunosuppressive therapy
6. Combined with malignant tumors
7. Drug addicts within half-one year before the test
8. Poor compliance to antiviral therapy; take part in other clinical trials at present

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Conventional treatment plus Allogeneic Adoptive Immune Therapy; Participants will receive conventional treatment (anti-opportunistic infections, cART and other treatments) plus a dose (2-3 times) of Allogeneic Adoptive Immune Therapy	Biological: Allogeneic Adoptive Immune Therapy; A dose (2-3 times) of AAIT was added on conventional treatment for advanced AIDS patients
No Intervention: Conventional treatment; Without Allogeneic Adoptive Immune Therapy but conventional treatment (anti-opportunistic infections , cART and other treatments) should be received

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change of CD4+ T cell count between AAIT treatment group and conventional group	Marker for host immunity	At Baseline , week 4,12, 24, 48 and 96
The change of survival between AAIT treatment group and conventional group	Marker for efficacy of treatment	At week 24, 48 and 96

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side effects in the AAIT treatment group	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	At Baseline, week 1, 2 , 4 and 24
The occurence of clinical events including AIDS-related events and non-AIDS related events in the two groups	Marker for efficacy of treatment	At baseline, week 24, 48, 84 and 96
The change of plasma RNA copies/mL between AAIT treatment group and conventional group	Marker for HIV viral load	At Baseline, week 1, 4, 12, 24, 48, 84 and 96
The change of plasma HIV DNA between AAIT treatment group and conventional group	Changes of HIV DNA in PBMC	At Baseline and week 1, 12, 24 and 48

Collaborators and Investigators

• Sponsor: Beijing 302 Hospital
• Collaborators: Shanghai Public Health Clinical Center; The 6th people's Hospital of Xinjiang province; The 4th people's hospital of Nanning City; The 3th people's hospital of Shenzhen City; Yunnan Provincial Hospital of Infectious Diseases
• Investigators: Study Director: Fu-Sheng Wang, MD, Beijing 302 Hospital

Publications and helpful links

General Publications

• Lane HC, Zunich KM, Wilson W, Cefali F, Easter M, Kovacs JA, Masur H, Leitman SF, Klein HG, Steis RG, et al. Syngeneic bone marrow transplantation and adoptive transfer of peripheral blood lymphocytes combined with zidovudine in human immunodeficiency virus (HIV) infection. Ann Intern Med. 1990 Oct 1;113(7):512-9. doi: 10.7326/0003-4819-113-7-512.
• Hutter G, Nowak D, Mossner M, Ganepola S, Mussig A, Allers K, Schneider T, Hofmann J, Kucherer C, Blau O, Blau IW, Hofmann WK, Thiel E. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med. 2009 Feb 12;360(7):692-8. doi: 10.1056/NEJMoa0802905.
• Lane HC, Masur H, Longo DL, Klein HG, Rook AH, Quinnan GV Jr, Steis RG, Macher A, Whalen G, Edgar LC, et al. Partial immune reconstitution in a patient with the acquired immunodeficiency syndrome. N Engl J Med. 1984 Oct 25;311(17):1099-103. doi: 10.1056/NEJM198410253111706. No abstract available.
• Kuritzkes DR. Hematopoietic stem cell transplantation for HIV cure. J Clin Invest. 2016 Feb;126(2):432-7. doi: 10.1172/JCI80563. Epub 2016 Jan 5.
• Krishnan A. Stem cell transplantation in HIV-infected patients. Curr Opin HIV AIDS. 2009 Jan;4(1):11-5. doi: 10.1097/COH.0b013e32831a6fc9.
• Davis KC, Hayward A, Ozturk G, Kohler PF. Lymphocyte transfusion in case of acquired immunodeficiency syndrome. Lancet. 1983 Mar 12;1(8324):599-600. doi: 10.1016/s0140-6736(83)92855-6. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2019
• Primary Completion (Estimated): December 30, 2023
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: August 29, 2019
• First Submitted That Met QC Criteria: September 19, 2019
• First Posted (Actual): September 23, 2019

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 2, 2024
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Safety; Immune Therapy; Efficiency; AIDS patients
• Other Study ID Numbers: 302-2019-05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No