Delayed infusion of a naïve T cell–depleted hematopoietic graft with memory T cells for 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

This early study will test whether giving a donor-derived stem cell graft that’s depleted of naïve T cells but includes memory T cells can safely help children and adults who receive kidney, lung, or multivisceral transplants tolerate the new organ with less long-term immune-suppressing medicine.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 0 Years and up
• Sex: All
• Sponsor: Hospital Universitario La Paz (Academic / other)
• Locations: 1 site (Madrid, Madrid)
• Trial ID: NCT06997471 on ClinicalTrials.gov

What this trial studies

This is a single-center, open-label Phase I study enrolling up to 10 pediatric and adult solid organ transplant recipients to test safety and feasibility. After transplant and a stabilization period, participants will receive low-dose preconditioning (total lymphoid irradiation and thymic irradiation) followed by infusion of a hematopoietic graft enriched for CD34+ progenitors, depleted of naïve T lymphocytes, and supplemented with memory T cells to induce mixed chimerism. The primary focus is safety and feasibility of the delayed graft infusion and monitoring for rejection, infection, and hematologic complications. Exploratory aims include signs of donor-derived chimerism and reduced dependence on long-term immunosuppression.

Who should consider this trial

Good fit: Ideal candidates are pediatric (<18) patients awaiting intestinal or lung transplantation and pediatric or adult (≥18) patients who are candidates for kidney transplantation or have recently had a kidney transplant and are eligible for hematopoietic stem cell transplantation, with no active infection or contraindicating medical conditions.

Not a fit: Patients with existing bone marrow disorders, active uncontrolled infections or autoimmune disease, or advanced cardiac, hepatic, or pulmonary dysfunction are unlikely to benefit or be eligible for this procedure.

Why it matters

Potential benefit: If successful, this approach could reduce or eliminate the need for lifelong immunosuppressive drugs and lower the risk of rejection and infection for transplant recipients.

How similar studies have performed: Mixed hematopoietic chimerism approaches have shown promising tolerance results in small kidney transplant programs, but the specific delayed infusion of a naïve T cell–depleted graft supplemented with memory T cells is a novel, early-phase strategy with limited prior clinical data.

Eligibility criteria

Inclusion Criteria:

* 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 Criteria:

* 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.

Where this trial is running

Madrid, Madrid

• La Paz University Hospital — Madrid, Madrid, Spain (Recruiting)

Study contacts

• Study coordinator: Francisco María Hernández Oliveros, MD, PhD

Conditions Solid Organ Transplant Complications; Solid Organ Transplant Recipients; Solid Organ Transplant Rejection