NCT06997471

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

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Sponsor: Francisco Hernández Oliveros · Academic / Other
• Sex: All
• Age: 0 Years
• Healthy volunteers: Not accepted

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.

Detailed description

This clinical trial is exploring a new way to help patients who receive a solid organ transplant-such as a kidney, lung, or intestine-live longer and healthier lives with fewer side effects from medication. Today, most transplant recipients must take strong immune-suppressing drugs every day to prevent their bodies from rejecting the new organ. While these drugs are essential, they can lead to serious complications over time, such as infections, and even damage to the transplanted organ itself. The goal of this study is to test a promising strategy that may help the body naturally accept the transplanted organ, reducing or potentially eliminating the need for long-term immunosuppressive drugs. This approach involves a technique called mixed hematopoietic chimerism, which means that the patient's body receives a mix of immune cells from both themselves and the organ donor. When successful, this blend of immune systems can lead to immune tolerance, allowing the transplanted organ to function without being attacked by the patient's immune system. This is a Phase I, single-center, open-label clinical trial, which means it is an early-stage study focused primarily on evaluating safety. The trial will enroll 10 patients who are either scheduled to receive a solid organ transplant (SOT) or have recently undergone one, depending on the type of organ and donor availability. After a transplant, each patient must go through a stabilization period, allowing time for any immediate post-surgical complications to improve. Once stabilized, the patient will receive a specially prepared infusion of blood-forming (hematopoietic) stem cells from their organ donor. This process is known as hematopoietic stem cell transplantation (HSCT). Before this infusion, patients will undergo low-dose preconditioning using total lymphoid irradiation (TLI) and thymic irradiation. These treatments prepare the body to accept the donor's cells without causing major immune damage, and they aim to lower the risk of complications like graft-versus-host disease (GVHD)-a serious condition where donor immune cells attack the patient's tissues. The infused cell product is carefully designed: * It includes CD34+ blood stem cells, which help rebuild the patient's immune and blood systems. * It removes "naïve" T cells (CD45RA+), which are known to cause GVHD. * It includes "memory" T cells (CD45RO+), which support immune recovery and protection against infections. In some cases, natural killer cells CD56+ may also be included to help protect against viruses and support tolerance-especially when the donor is haploidentical. The way the cells are collected depends on whether the donor is living or deceased. For living donors, peripheral blood stem cells are collected. For deceased donors, the bone marrow is used. This trial is based on encouraging results from earlier studies and aims to show that this strategy is safe and feasible. If successful, the benefits could be wide-ranging: * Less dependence on lifelong immunosuppressive medications * Lower risk of chronic rejection of the transplanted organ * Fewer life-threatening infections * Improved quality of life, especially for children and young adults * Increased availability of transplantable organs by improving outcomes and reducing re-transplantation needs * Lower healthcare costs due to fewer complications, hospitalizations, and medications The study will also track how well the patient's body accepts the transplanted organ over time and whether true immune tolerance is achieved. This will be monitored by looking at immune markers in the blood and through regular clinical follow-ups. This approach could be especially helpful for pediatric patients, who face unique challenges, such as difficulty adhering to lifelong medication plans and a higher risk of needing multiple transplants. It may also help adult patients at high risk of rejection, or those who have already had complications with previous transplants.

Conditions

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

Interventions

Type	Name	Description
BIOLOGICAL	Investigational 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

Timeline

• Start date: 2025-06-01
• Primary completion: 2028-06-01
• Completion: 2028-06-01
• First posted: 2025-05-30
• Last updated: 2025-05-30