Clinical trial NCT04098770: Allogeneic Adoptive Immune Therapy for Advanced AIDS Patients
Official title: Safety and Efficiency of Allogeneic Adoptive Immune Therapy for Advanced AIDS Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: AIDS Patients
Keywords: AIDS patients
Safety
Efficiency
Immune Therapy
Lead sponsor: Beijing 302 Hospital
Sponsor class: OTHER
Collaborators: name: The 6th people's Hospital of Xinjiang province
name: The 4th people's hospital of Nanning City
name: The 3th people's hospital of Shenzhen City
name: Shanghai Public Health Clinical Center
name: Yunnan Provincial Hospital of Infectious Diseases
First posted: 2019-09-23
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: The change of CD4+ T cell count between AAIT treatment group and conventional group
timeFrame: At Baseline , week 4,12, 24, 48 and 96
measure: The change of survival between AAIT treatment group and conventional group
timeFrame: At week 24, 48 and 96
Secondary outcomes:
Other outcomes:
measure: Side effects in the AAIT treatment group
timeFrame: At Baseline, week 1, 2 , 4 and 24
measure: The occurence of clinical events including AIDS-related events and non-AIDS related events in the two groups
timeFrame: At baseline, week 24, 48, 84 and 96
measure: The change of plasma RNA copies/mL between AAIT treatment group and conventional group
timeFrame: At Baseline, week 1, 4, 12, 24, 48, 84 and 96
measure: The change of plasma HIV DNA between AAIT treatment group and conventional group
timeFrame: At Baseline and week 1, 12, 24 and 48
Locations:
city: Beijing
country: China
facility: Beijing 302 Hospital of China
state: Beijing
Study officials:
affiliation: Beijing 302 Hospital
name: Fu-Sheng Wang, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: Krishnan A. Stem cell transplantation in HIV-infected patients. Curr Opin HIV AIDS. 2009 Jan;4(1):11-5. doi: 10.1097/COH.0b013e32831a6fc9.
citation: 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.
citation: 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.
citation: 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.