RecruitingPhase 1NCT06997471

Phase I Trial on the Safety of Delayed Infusion of a Naïve T Cell-Depleted Hematopoietic Graft With Memory T Cells in Solid Organ Transplant Recipients

A Phase I, Single-Center, Open-Label Trial to Assess the Safety and Tolerability of Delayed Infusion of a Naïve T Cell Depleted Hematopoietic Graft and Memory T-lymphocytes in Recipients of Solid Organ Transplantation

Sponsor

Francisco Hernández Oliveros

Enrollment

10 participants

Start Date

Jun 10, 2025

Study Type

INTERVENTIONAL

Conditions

Solid Organ Transplant Complications Solid Organ Transplant Recipients Solid Organ Transplant Rejection

Summary

The goal of this clinical trial is to evaluate the safety and feasibility of inducing hematopoietic mixed chimerism to promote immune tolerance and potentially reduce the need for lifelong immunosuppression in pediatric and adult patients undergoing solid organ transplantation (SOT), including kidney, lung, and multivisceral transplants. The main questions it aims to answer are: * Is it safe to infuse a naïve T cell-depleted hematopoietic graft along with memory T-lymphocytes after SOT? * Can this approach support immune tolerance and reduce the incidence of rejection and infection without long-term immunosuppression? Participants will: * Undergo a solid organ transplant from a living or deceased donor. * Wait through a stabilization period to ensure resolution of early transplant-related complications. * Receive low-dose preconditioning (TLI and thymic irradiation) to prepare for hematopoietic stem cell transplantation. * Be infused with a graft containing CD34+ progenitor cells, memory T cells (CD45RO+), and no naïve T cells (CD45RA+); in some cases, NK cells may also be included. * Be followed for graft survival, immune tolerance, infection rates, and adverse events through regular clinical and immune monitoring visits.

Eligibility

Min Age: 0 Years

Inclusion Criteria4

Pediatric patients (<18 years old) who are candidates to receive intestinal or lung transplantation (before SOT).
Pediatric (<18 years old) or adult patients (≥18 years old) who are either candidates for renal transplantation or have already undergone renal transplantation and remain candidates for subsequent HSCT.
Patients who provide informed consent (or their legal guardians in the case of minors) before any study-related procedures.
Recipients should have no active infectious disease or other medical condition that would contraindicate the combined transplantation procedure, as determined by the investigational team.

Exclusion Criteria8

Recipients with existing bone marrow disorders or those receiving medications known to adversely affect bone marrow function.
Patients with advanced organ dysfunction (hepatic, cardiac, or pulmonary) incompatible with successful combined transplantation.
Patients with active or uncontrolled autoimmune conditions that may interfere with transplantation and the induction of chimerism.
Patients with known allergies to medications or products required for conditioning or transplantation.
Patients with severe psychiatric or cognitive disorders that may interfere with adherence to study instructions or postoperative care.
Patients currently enrolled in another clinical trial that could interfere with the outcomes or safety of this study.
Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
Any other condition that, in the opinion if the Investigator, may interfere with the efficacy and/or safety evaluation of the trial.

Interested in this trial?

Get notified about updates and connect with the research team.

Interventions

BIOLOGICALInvestigational cellular therapy consisting on a HSCT using a graft enriched in CD34+, depleted of naïve T-lymphocytes and supplemented with memory lymphocytes

Infusion Schedule 1. Primary Infusion: the enriched graft, containing the CD34+ progenitors and depleted naïve T cells, will be infused after the patient has undergone conditioning therapy. 2. In the case of haploidentical donors, an additional NK cell infusion will be administered whenever possible around day 7 post-transplant from a non-mobilized apheresis collection, aiming to enhance graft tolerance and prevente HHV6 disease. 3. Post-Transplant Memory T cell Infusions: beginning on days 15 and 30, and then administered monthly up to a maximum of one year or until the supply is depleted, memory T cells will be infused. Conditioning Regimen Prior to HSCT, all patients will undergo a low-intensity conditioning regimen designed to allow engraftment of the donor cells while minimizing toxicity: 1. Total Lymphoid Irradiation (TLI): 8 Gy of total lymphoid irradiation will be administered. 2. Fludarabine: a total dose of 120 mg/m², spread over 4 days (-6 to -3 before transplant), will serv