Allogeneic Adoptive Immune Therapy for Advanced AIDS Patients

NCT ID: NCT04098770

Last Updated: 2024-01-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

240 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-11

Study Completion Date

2024-12-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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AIDS Patients

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

Allogeneic Adoptive Immune Therapy

Intervention Type BIOLOGICAL

A dose (2-3 times) of AAIT was added on conventional treatment for advanced AIDS patients

Conventional treatment

Without Allogeneic Adoptive Immune Therapy but conventional treatment (anti-opportunistic infections , cART and other treatments) should be received

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Allogeneic Adoptive Immune Therapy

A dose (2-3 times) of AAIT was added on conventional treatment for advanced AIDS patients

Intervention Type BIOLOGICAL

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The 6th people's Hospital of Xinjiang province

UNKNOWN

Sponsor Role collaborator

The 4th people's hospital of Nanning City

UNKNOWN

Sponsor Role collaborator

The 3th people's hospital of Shenzhen City

UNKNOWN

Sponsor Role collaborator

Shanghai Public Health Clinical Center

OTHER_GOV

Sponsor Role collaborator

Yunnan Provincial Hospital of Infectious Diseases

UNKNOWN

Sponsor Role collaborator

Beijing 302 Hospital

OTHER

Sponsor Role lead

Responsible Party

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Fu-Sheng Wang

Head of Treatment and Research Center for Infectious Diseases, Principle Investigator, Clinical Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Fu-Sheng Wang, MD

Role: STUDY_DIRECTOR

Beijing 302 Hospital

Locations

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Beijing 302 Hospital of China

Beijing, Beijing Municipality, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Ruonan Xu, MD

Role: CONTACT

86-10-66933333

Facility Contacts

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Fu-Sheng Wang, MD

Role: primary

01066933328

References

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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.

Reference Type BACKGROUND
PMID: 26731468 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19213682 (View on PubMed)

Krishnan A. Stem cell transplantation in HIV-infected patients. Curr Opin HIV AIDS. 2009 Jan;4(1):11-5. doi: 10.1097/COH.0b013e32831a6fc9.

Reference Type BACKGROUND
PMID: 19339935 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 6131294 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 6384784 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1975487 (View on PubMed)

Yang T, Xie Z, Xu Z, Tu B, Lu H, Huang H, Huang L, Zhang C, Gao L, Jin L, Ma P, Zou J, Liu L, Zhen C, Zhou C, Meng S, Li YY, Song JW, Yang S, Ai HS, Jiao Y, Shi M, Xu R, Wang FS. HLA-mismatched allogeneic adoptive immune therapy in patients with severely immunosuppressed AIDS: a multicenter, open-label, controlled, phase 2a study. Emerg Microbes Infect. 2024 Dec;13(1):2364744. doi: 10.1080/22221751.2024.2364744. Epub 2024 Jun 27.

Reference Type DERIVED
PMID: 38935839 (View on PubMed)

Other Identifiers

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302-2019-05

Identifier Type: -

Identifier Source: org_study_id

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