Clinical trial NCT02923076: HIV Eradication Through Cord-blood Transplantation
Official title: A Prospective Clinical Research Protocol of Allogeneic CCR5 delta32/delta32 Cord Blood Cell Transplantation to Cure HIV Infection
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: HIV
Keywords: Allogeneic Hematopoietic Cell Transplantation
Lead sponsor: Puerta de Hierro University Hospital
Sponsor class: OTHER
Collaborators: name: Fundación Mutua Madrileña
name: Instituto de Salud Carlos III
First posted: 2016-10-04
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Allogeneic hematopoietic cell transplantation from a CCR5 Δ32/Δ32 unrelated donor, performed for the first time in the "Berlin patient", provides the only evidence to date of long-term control of HIV infection. Stringent criteria to select human leukocyte antigen (HLA)-matched conventional donors and low prevalence of the CCR5 Δ32/Δ32 homozygous genotype (\<1%) made the pursuit of "patient number 2" unsuccessful for many years. Cord blood (CB) transplantation allows more permissive HLA-matching criteria, making the search for HLA-compatible Δ32/Δ32 CB units potentially feasible for transplantation of HIV-infected individuals.

The investigator team involved in this trial has recently reported the first such case of CCR5 delta32/delta32 CB transplantation in a patient with HIV infection, showing a reduction of the patient's latent viral reservoir and, upon achievement of full CB chimerism, resistance of his CD4 T-lymphocytes to infection by HIV. This proof of concept led the Spanish National Transplant Organization (ONT) to generate an inventory of over 150 CCR5 Δ32/Δ32 CB units readily available for transplant.

From this initial evidence and repository of CB units, financial support from the Fundación Mutua Madrileña (FMM) has allowed the investigators to launch this first pilot clinical trial in this indication. The study was launched in January 2016 at Hospital Universitario Puerta de Hierro Majadahonda. All HIV virology and reservoir analyses are carried out by the AIDS Immunopathology Unit at the Spanish Instituto de Salud Carlos III. Three additional transplant centres in Spain will also shortly open the trial.


Eligibility criteria: Inclusion Criteria:

* Inform consent, that will be previously approved by the board, is required in order to carry out any procedure related to the study.
* HIV infection.
* Hematologic malignancies or any other condition with a standard indication for allogeneic hematopoietic cell transplantation. See indications by the European Society for Blood and Marrow Transplantation (EBMT). \[Sureda A. et al. Indications for allo- and auto-SCT for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2015. Bone Marrow Transplantation (2015) 50, 1037-1056.\]
* Lack of HLA-identical related donor
* Availability of at least one cord blood unit CCR5 delta32 homozygous that meets quality standards.

Exclusion Criteria:

* Availability of HLA-identical related donor
* Contraindication for allogeneic stem cell transplantation.

Primary outcomes:
measure: HIV infection and viral reservoir - Cell-associated total HIV-1 DNA in CD4 T cells from peripheral blood and from gut-associated lymphoid tissue (GALT): Expressed in copies per million cells.
timeFrame: Between 6-12 months: following discontinuation of antiretroviral therapy upon full CCR5 delta32/delta32 cord blood chimerism
measure: HIV infection and viral reservoir - Viral copies in plasma and culture supernatants by Single Copy Assay and COBAS AMPLICOR HIV-1 Monitor v.1.5: Expressed in copies per mL.
timeFrame: Between 6-12 months: following discontinuation of antiretroviral therapy upon full CCR5 delta32/delta32 cord blood chimerism
measure: Ex vivo HIV-1 infection tests on CCR5 d32/d32-derived recipients CD4 T cells - Using patient's primary isolates and laboratory strains of HIV-1 with CCR5 and CXCR4 tropism: Expressed in ng/mL of p24 ELISA.
timeFrame: Between 6-12 months: following discontinuation of antiretroviral therapy upon full CCR5 delta32/delta32 cord blood chimerism
Secondary outcomes:
Other outcomes:
Locations:
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro- Majadahonda
state: Madrid
Study officials:
affiliation: Hospital Universitario Puerta de Hierro- Majadahonda
name: Rafael Duarte Palomino
role: PRINCIPAL_INVESTIGATOR
References: