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

NCT04804891 | Recruiting Phase 1 FDA Drug

• 1 other identifier: AAAS8908
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate the safety and feasibility of giving intestinal transplant patients CD34+ stem cells (the cells that make all the types of blood cells) obtained from their organ donor's bone marrow. The goal of this is to develop a post-transplant treatment strategy that controls rejection while reducing the high risk of infection and malignant disease associated with the high levels of immunosuppression medication(s) that intestinal and multi-organ transplant patients must take. Infusion of bone marrow cells from the same donor of the transplanted organ(s) could promote a state called "mixed chimerism" in which both donor cells and recipient cells coexist in the body with the ultimate goal of minimizing the amount of immunosuppression medication(s) needed.

Conditions

Intestinal Transplantation

Keywords

CD34+ stem cells; Chimerism; Bone marrow stells

Outcome Measures

Primary Outcomes (1)

• Total number of participants with moderate to severe GVHD

  Total number of participants with moderate to severe (at least Grade II) graft-versus-host disease (GVHD) will be monitored.

  Up to 4 years after transplantation

Secondary Outcomes (6)

• Graft survival rate

  Up to 1 month after transplantation

• Retention rate

  Up to 1 month after transplantation

• Graft survival rate

  Up to 1 year after transplantation

• Retention rate

  Up to 1 year after transplantation

• Graft survival rate

  Up to 3 years after transplantation

Study Arms (2)

Cell Therapy

EXPERIMENTAL

Patients will receive an infusion containing 1x106/kg CD34+ cells. No more than 104 CD34+ T cells per kg recipient weight will be included in the infusion. Cadaveric donor CD34 cell infusion will occur at any time between post-operative day 11 to day 13 following transplantation.

Biological: Cell Therapy

Control

NO INTERVENTION

Patients who do not consent to receive donor CD34 cell infusion or whose donor family declines consent for research use of donor bone marrow will receive their usual standard of care.

Interventions

Cell Therapy BIOLOGICAL

Infusion of containing 1x106/kg CD34+ cells from donor bone marrow selected using the CliniMACS® CD34 Reagent System.

Cell Therapy

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Tufting Enteropathy
• Complete portomesenteric thrombosis with cirrhosis
• Slow-growing, low-malignancy potential tumors infiltrating mesenteric root:
• Gardner's Syndrome

You may not qualify if:

• 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

Sponsors & Collaborators

• Columbia University: lead
• Ossium Health, Inc.: collaborator

Study Sites (1)

Columbia University Irving Medical Center/NYP

New York, New York, 10032, United States

RECRUITING

MeSH Terms

Interventions

Cell- and Tissue-Based Therapy

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Tomoaki Kato, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Research Core

CONTACT

212-305-3839; tk2388@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2021
• First Posted: March 18, 2021
• Study Start: October 22, 2021
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 1, 2026

Record last verified: 2026-03

Locations

US (1)