Clinical trial NCT02651376: Safety and Efficacy of Allogenic Adoptive Immune Therapy for Advanced AIDS Patients
Official title: Safety and Efficacy of Allogenic Adoptive Immune Therapy for Advanced AIDS Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Human Immunodeficiency Virus
Immunodeficiency
Keywords: Immunodeficiency
Allogenic Mononuclear Cell Transplantation
Lead sponsor: Beijing 302 Hospital
Sponsor class: OTHER
First posted: 2016-01-11
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Combined antiretroviral therapy (cART) efficiently suppress viral replication in majority of AIDS patients. The morbidity and mortality of the disease has dramatically decreased over the past 20 years. However, chronic human immunodeficiency virus-1 (HIV-1) infection lead to profound immune defects in some advanced AIDS patients who often develop with severe opportunistic infections (OIs), severe cachexia and other deadly complications, which accounts for the major death group even under cART. Up-to-date, there are no effective immune interventions to restore host holistic immunity for advanced AIDS patients.

Detailed description: Advanced AIDS patients are usually characterized with CD4 T cells less than 200 cells/uL, including end-stage AIDS patients (CD4 T cells less than 50 cells/uL), and often accompanied with severe opportunistic infections (including tuberculosis, PCP, fungus and so on) and deadly complications.In this regard, advanced AIDS patients present a unique and special profound immune deficiency setting. Therefore, increasing attention and evidence have been paid to development of novel immune therapeutic strategies for those patients.

Immune cell therapy in combination with anti-infection and anti-HIV therapy may open a new direction for advanced AIDS patients, but single cell-based immune therapies do not work well for advanced AIDS patients. Over past 30 years, more than hundreds of AIDS patients with haematological malignancies received autologous or allogeneic hematopoietic stem cell transfusion (HSCT), and their survival rate had been improved to the levels equal to non-HIV patients; however, allogeneic HSCT is only limited to treat AIDS patients with lymphoma or leukemia. The only cured Berlin Patient, who suffered from both acute myeloid leukemia and chronic HIV-1 infection, was transplanted with homozygous CCR5 delta 32 allogeneic HLA-matched stem cells and acquired a long-term remission of both leukemia and AIDS. However, it is very difficult to find the HLA-identical HSCT with CCR5 delta 32 homogenous donors for AIDS patients in clinic. 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 advanced AIDS patients, to the degree similar as the allogeneic HSCT for leukemia patients.

The purpose of this study is to investigate the safety and initial efficacy of allogeneic adoptive immune therapy (AAIT) for advanced AIDS patients. 20 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 (anti-opportunistic infection and ART) treatment for AIDS. The side effects, symptom improvement, control of opportunistic infections and CD4 T cell numbers will be evaluated during the 48-week follow up.

Eligibility criteria: Inclusion Criteria:

1. Severe immunodeficiency patients with chronic HIV-1 infection
2. 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
3. With or withour serious complications
4. Ability and willingness to provide informed consent

Exclusion Criteria:

1. Combined with other serious organic diseases, mental illness, including any uncontrolled clinical significance of urinary, respiratory, circulation, nerve, spirit, digestive, endocrine and immune system disease, lymphoma, malignant tumor of blood system etc;
2. Pregnancy, lactation and those who are not pregnant but do not take effective contraceptives measures
3. Allergic to blood products
4. Drug addicts within one year before the test
5. Poor compliance to antiviral therapy; take part in other clinical trials at present, may be contrary to the treatment plan; unable or unwilling to provide informed
6. Other serious conditions that may hamper clinical trials

Primary outcomes:
measure: Side effects
timeFrame: At Baseline and week 1, 2, 3, 4, 8, 12, 16, 24, 48
Secondary outcomes:
measure: The changes of clinical symptoms
timeFrame: At Baseline and week 1, 2, 3, 4, 8, 12, 16, 24,48
measure: The changes of CD4 T cell counts
timeFrame: At Baseline and week 1, 2, 3, 4, 8, 12, 16, 24, 48
measure: The plasma RNA copies/mL
timeFrame: At Baseline and at week 4, 12, 24, 48
Other outcomes:
Locations:
Study officials:
affiliation: Beijing 302 Hospital
name: Fu-Sheng Wang
role: PRINCIPAL_INVESTIGATOR
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. 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.
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: 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.