Using donor stem cells to reduce immunosuppression in intestinal transplant patients

Using T-Cell Alloreactivity and Chimerism to Guide Immunosuppression Minimization in Intestinal Transplantation

This study is testing whether using stem cells from organ donors can help people who have had intestinal transplants need less medication to suppress their immune system.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 6 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Columbia University (other)
• Locations: 1 site (New York, New York)
• Trial ID: NCT04804891 on ClinicalTrials.gov

What this trial studies

This study investigates the safety and feasibility of administering CD34+ stem cells from the bone marrow of organ donors to patients receiving intestinal transplants. The goal is to promote a state of mixed chimerism, where both donor and recipient cells coexist, potentially leading to immune tolerance and reducing the need for high levels of immunosuppression. By minimizing immunosuppressive medication, the study aims to lower the risk of infections and malignancies associated with current treatment protocols. The research is being conducted at Columbia University Irving Medical Center.

Who should consider this trial

Good fit: Ideal candidates include patients actively listed for intestinal or multi-visceral transplantation with conditions such as Short Bowel Syndrome or chronic intestinal pseudo-obstruction.

Not a fit: Patients who are not candidates for intestinal or multi-visceral transplantation or those with contraindications to stem cell therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve the long-term outcomes and quality of life for intestinal transplant patients by reducing the risks associated with immunosuppression.

How similar studies have performed: Previous studies have shown promise in using mixed chimerism to induce tolerance in kidney transplant patients, suggesting potential applicability in intestinal transplantation.

Eligibility criteria

Inclusion Criteria:

* All patients actively listed as candidates for intestinal or multi-visceral transplant at the study site; while all patients who are actively listed in United Network for Organ Sharing (UNOS) for intestinal and/or multi-visceral transplantation, including those who have previously received a multi-visceral transplant and are re-listed, are eligible for participation, the following are examples of listing criteria suitable for enrollment in this clinical trial:

  * Short Bowel Syndrome (SBS) due to:

    * Trauma (multiple resections/explorations and/or vascular abdominal trauma superior mesenteric artery (SMA) / superior mesenteric vein (SMV) injuries)
    * Gastroschisis
    * Volvulus
    * Necrotizing Enterocolitis
    * Intestinal Atresia
    * Crohn's Disease
    * Hirschprung's Disease
  * Chronic Intestinal Pseudo-Obstruction
  * Malabsorption:

    * Microvillus Inclusion Disease
    * Tufting Enteropathy
    * Complete portomesenteric thrombosis with cirrhosis
  * Slow-growing, low-malignancy potential tumors infiltrating mesenteric root:

    * Gardner's Syndrome
    * Familial Adenomatous Polyposis
    * Desmoid Tumor with Intra-Abdominal Infiltration
    * Endocrine Tumors
  * Re-transplant candidates who lost the first graft to rejection or patients who have higher risk of toxicity from chronic long term immunosuppression (i.e., patients with chronic kidney disease)
* Patient commits to planned follow up at a study site for the 48-month duration of study procedures
* Age ≥18 years old and ≤65 years old
* Subjects or capable of signing the informed consent document themselves

Exclusion Criteria:

* Active systemic infection with hemodynamic instability and/or sepsis
* Patients with known immunodeficiency syndrome
* Carcinoma with metastasis (except neuro-endocrine tumors, even in the presence of metastasis these patients may undergo multivisceral/cluster transplantation)
* Severe cardiovascular and/or respiratory instability, as defined by requirement of pressors or ventilator
* Severe cerebral edema, with radiologic findings of effaced sulci and/or herniation
* Poorly controlled hypertension (systolic blood pressure \> 170 on at least 2 occasions), diabetes mellitus (HbA1c \> 8), or uncontrollable seizure disorders
* Age \> 65 years
* Documented history of non-compliance with medical therapy and follow-up
* Substance addiction in the last six months
* Psychosocial Instability: absence of a consistent reliable social support system
* Significant or active psychiatric disorder associated with the inability to cooperate or comply with medical therapy
* In the judgement of the clinical team, severely limited functional status with poor rehabilitation potential
* Multi-organ failure and preceding CD34+ infusion
* Pre formed panel reactive antibodies (PRA) mean fluorescein intensity (MFI) \> 5000 by Luminex
* Patients who are pregnant or breast-feeding or intend to get pregnant during the study period
* Patients who have developed moderate or severe rejection before post-transplant day 11
* Vulnerable populations, such as incarcerated or institutionalized individuals
* Subjects with clinical features suggestive of GVHD
* Subjects who are hemodynamically unstable (i.e., requiring vasopressor support)
* Female subjects of childbearing age and male patients who are not using and/or unwilling to use an effective method of birth control for the duration of the trial activities
* History of previous hematopoietic progenitor cell (HPC) infusion or transplant of any kind. Note: Human leukocyte antigen (HLA) mismatch will not be one of the exclusion criteria

Where this trial is running

New York, New York

• Columbia University Irving Medical Center/NYP — New York, New York, United States (RECRUITING)

Study contacts

• Principal investigator: Tomoaki Kato, MD — Columbia University
• Study coordinator: Clinical Research Core

Conditions: Intestinal Transplantation, CD34+ stem cells, Chimerism, Bone marrow stells