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Phase 1b/2a Trial of Allogeneic HSCT From an HLA-partially Matched Related or Unrelated Donor After TCRab+ T-cell/CD19+ B-cell Depletion for Patients With Monogenic and/or Early-onset Medically Refractory Crohn Disease | Clinical Trials | Clareo Health

NOT_YET_RECRUITINGPHASE1/PHASE2

Phase 1b/2a Trial of Allogeneic HSCT From an HLA-partially Matched Related or Unrelated Donor After TCRab+ T-cell/CD19+ B-cell Depletion for Patients With Monogenic and/or Early-onset Medically Refractory Crohn Disease

Phase 1b/2a Trial of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) From an HLA-partially Matched Related or Unrelated Donor After TCRab+ T-cell/CD19+ B-cell Depletion for Patients With Monogenic and/or Early-onset (EO), Medically Refractory (MR) Crohn Disease (CD)

NCT06986382•Stanford University

View on ClinicalTrials.gov

Summary

This research study is investigating whether alpha beta T-cell depleted hematopoietic stem cell transplant (HSCT) can be an immune system replacement for Crohn disease patients and whether this is safe and effective for patients with early onset, medically refractory Crohn disease.

Detailed Description

This is a single center, non-randomized, non-controlled open-label Phase 1b/2a trial to study the safety and efficacy of performing TCRαβ+ T-cell/CD19+ B-cell depleted (TCRαβ-depleted) HSCT to induce immune tolerance in patients with monogenic or early onset, medically refractory Crohn disease to re-establish normal immune-intestinal homeostasis.

Eligibility

Age

2 - 30 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1\. Meets at least one of the following criteria:
•a. Known monogenic ("Mendelian") cause of IBD for which HSCT has been successfully performed i. Causative gene mutation known for which HSCT is demonstrated to be curative (e.g., IL10, IL10RA, IL10RB, XIAP, IPEX, WAS, CD40L, CGD, LRBA, CTLA4, DOCK8 and SCID syndromes).
•b. Known monogenic cause of CD for which HSCT has not been previously performed i. Causative gene mutation expressed in lymphohematopoietic cells, for which HSCT has not been previously performed; AND ii. Moderate disease activity (shown through endoscopic, MRI, or PCDAI score); AND iii. Has been treated with at least two available treatment pathways (e.g., TNF inhibitors, anti-IL12 and /or IL-23 antibodies, JAK inhibitors, anti-integrin), but did not have adequate response, experienced significant toxicity, or had adverse effect(s) c. Suspected monogenic cause of CD i. Rare variant in a gene predicted to be functionally deleterious, suspected to drive IBD, and expressed in lymphohematopoietic cells; AND ii. Moderate disease activity or corticosteroid-dependence despite trials of at least two biologic or small molecule therapies of different mechanisms or significant toxicity or adverse effect related to such medical therapy.
•d. Medically refractory CD with suspected strong genetic component, but no clearly identified deleterious single gene mutation.
•i. Moderate or severe disease activity with either:
•1. history of corticosteroid-dependence despite trials of at least two biologic or small molecule therapies of different mechanisms,
•2. significant toxicity, or adverse effects related to such medical therapy;
•AND at least one of the following criteria from ii or iii below:
•ii. Severity unlikely to be tolerable long-term due to the presence of either:
•1. Disease not amenable to surgical therapy without risk of short bowel syndrome or permanent ileostomy;
+6 more criteria

Exclusion Criteria

•1. Ulcerative colitis
•2. CD and associated extraintestinal manifestations responsive to medical therapy without corticosteroid-dependence or significant toxicity or adverse effects
•3. Known or suspected functionally deleterious mutation in a gene that meets either of the following expression criteria:
•1. Specifically expressed in epithelial or stromal cells, but not expressed in lymphohematopoietic cells (e.g., TTC7A)
•2. Expected to be more functionally deleterious in cell types other than lymphohematopoietic cells than in lymphohematopoietic cell types
•4. Active hemophagocytic lymphohistiocytosis (HLH). Patients with a history of hemophagocytic lymphohistiocytosis (HLH) are eligible, if there is no current clinical, histological, or biochemical evidence of HLH activity.
•5. Dysfunction of liver, defined as:
•1. ALT/AST \> 5 times upper normal value, or direct bilirubin \> 3 times upper normal value; or
•2. Cirrhosis with bridging fibrosis (grade F3 or greater) or sclerosing cholangitis
•6. Severe cardiovascular disease (e.g. left ventricular ejection fraction \< 40%), or clinical or echocardiographic evidence of severe diastolic dysfunction.
+8 more criteria

Locations (1)

Lucile Packard Children's Hospital

Palo Alto, California, United States

Key Dates

Start Date

July 1, 2025

Primary Completion Date

July 1, 2037

Completion Date

July 1, 2040

Last Updated

May 23, 2025

Enrollment

ESTIMATED participants

Conditions

Crohn Disease

Interventions

CliniMACS® TCR α/β Reagent Kit and CliniMACS® CD19 System

DEVICE

Prednisone/Methylprenisolone

DRUG

Palifermin

DRUG

ATG

DRUG

Clofarabine

DRUG

Melphalan

DRUG

Total Body Irradiation

RADIATION

Rituximab

DRUG

Switching to the IL-23 Inhibitor Guselkumab for People With Active IBD Who Previously Used Ustekinumab (SHIFT-IBD)

NCT07245394

Inflammatory Bowel Disease (IBD)Crohn Disease (CD)+2 more

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RECRUITING

ALPCO/Calprotectin CLIA Assay: Expected Values of Calprotectin in Healthy Subjects

NCT07089420

IBD (Inflammatory Bowel Disease)IBS - Irritable Bowel Syndrome+2 more

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: May 23, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Phase 1b/2a Trial of Allogeneic HSCT From an HLA-partially Matched Related or Unrelated Donor After TCRab+ T-cell/CD19+ B-cell Depletion for Patients With Monogenic and/or Early-onset Medically Refractory Crohn Disease

Inclusion Criteria

Exclusion Criteria

Switching to the IL-23 Inhibitor Guselkumab for People With Active IBD Who Previously Used Ustekinumab (SHIFT-IBD)

ALPCO/Calprotectin CLIA Assay: Expected Values of Calprotectin in Healthy Subjects

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