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Crohn DiseasePhase 1/2NCT06986382

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

A Phase 1/2 study testing CliniMACS® TCR α/β Reagent Kit and CliniMACS® CD19 System, Prednisone/Methylprenisolone and Palifermin in people with Crohn Disease, run by Stanford University at 1 site in United States.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 2 to 30 years
Conditions the study is for
Crohn Disease
What is being tested?
CliniMACS® TCR α/β Reagent Kit and CliniMACS® CD19 System, Prednisone/Methylprenisolone and Palifermin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
1 siteUnited States
Study dates
Jul 2025to Jul 2040
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Recipient Inclusion Criteria:

  1. Meets at least one of the following criteria:
  2. 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).
  3. 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.
  4. Medically refractory CD with suspected strong genetic component, but no clearly identified deleterious single gene mutation.
  5. Moderate or severe disease activity with either:
  6. history of corticosteroid-dependence despite trials of at least two biologic or small molecule therapies of different mechanisms,
  7. 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;
  2. Requirement for long-term parenteral nutrition;
  3. Intolerable extraintestinal symptoms (e.g., arthritis, dermatitis); iii. Presence of any of the following features associated with high genetic contribution to disease:
  4. Parental consanguinity 2. Strong family history of IBD (present in first degree relatives) 3. Diagnosis earlier than 6 years of age 4. Extraintestinal manifestations 5. Family history of CD, IBD or autoimmune disease 2. Age >2 year and < 30 years. 3. The donor and recipient must be identical, as determined by high resolution typing, at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DQB1 and HLA-DRB1.
  5. Lansky/Karnofsky score ≥50; the Karnofsky Scale will be used in subjects ≥ 16 years of age, and the Lansky Scale will be used for those < 16 years of age.
  6. All subjects ≥ 18 years of age must be able to give informed consent, or adults lacking capacity to consent must have a legally authorized representative (LAR) available to provide consent. For subjects <18 years old their legal authorized representative (LAR) (i.e. parent or guardian) must give informed consent. Pediatric subjects will be included in age-appropriate discussion and written assent will be obtained for those > 7 years of age, when appropriate.
  7. Female subjects of childbearing potential must agree to use an effective means of birth control to avoid pregnancy throughout the transplant procedure, while on immunosuppression.

Recipient 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:
  4. Specifically expressed in epithelial or stromal cells, but not expressed in lymphohematopoietic cells (e.g., TTC7A)
  5. Expected to be more functionally deleterious in cell types other than lymphohematopoietic cells than in lymphohematopoietic cell types
  6. 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.
  7. Dysfunction of liver, defined as:
  8. ALT/AST > 5 times upper normal value, or direct bilirubin > 3 times upper normal value; or
  9. Cirrhosis with bridging fibrosis (grade F3 or greater) or sclerosing cholangitis
  10. Severe cardiovascular disease (e.g. left ventricular ejection fraction < 40%), or clinical or echocardiographic evidence of severe diastolic dysfunction.
  11. Severe renal dysfunction defined as serum creatinine >1.5 X upper limit of normal (ULN) or 24-hour creatinine clearance <50 ml/min/m2
  12. Human immunodeficiency virus (HIV)-infected patients or patients with evidence of chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
  13. Past exposure to therapeutic radiation.
  14. Previous allogeneic HSCT. Patients who have received previous autologous HSCT are eligible.
  15. Active malignancy and patients who have history of malignancies, unless disease free for at least 2 years, with the exception of nonmelanoma skin cancer or carcinoma in situ (e.g., bladder, breast).
  16. Pregnant or lactating females.
  17. Lack of patient/parent/guardian informed consent.
  18. Any severe concurrent uncontrolled disease which, in the judgement of the investigator, would place the patient at increased risk during participation in the study, other than primary disease.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site

  • Lucile Packard Children's Hospital

    Palo Alto, California, 94305

Other trials in United States

About this study

Official title: 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)

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.

Read the 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.

Conditions
Crohn Disease
Being tested
CliniMACS® TCR α/β Reagent Kit and CliniMACS® CD19 System, Prednisone/Methylprenisolone, Palifermin, ATG, Clofarabine
Medical subject headings
Crohn Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CliniMACS® TCR α/β Reagent Kit and CliniMACS® CD19 SystemDevice

    Also called TCRαβ+ T-cells

    CliniMACS® TCRαβ-Biotin and CD19 Systems will be used to create the mobilized peripheral blood stem cells (PBSC) from allogeneic donors depleted of TCRαβ+ T cells and CD19+ B cells to be infused into the patient for the HSCT. The target dose for the number of CD34+ HSC infused is > 10 x 10^6 cells/Kg recipient weight. The minimum dose is 2 x 10^6 cells/Kg. There is no upper limit to the dose of CD34+ HSC infused as long as no more than 1 x 10^5 TCRαβ+ T-cells/Kg are infused. The target dose of TCRαβ+ T cells/Kg is < 0.50 x 10^5.

  • Prednisone/MethylprenisoloneDrug

    Administered as part of the HSCT conditioning regimen

  • PaliferminDrug

    Administered as part of the HSCT conditioning regimen

  • ATGDrug

    Administered as part of the HSCT conditioning regimen

  • ClofarabineDrug

    Administered as part of the HSCT conditioning regimen

  • MelphalanDrug

    Administered as part of the HSCT conditioning regimen

  • Total Body IrradiationRadiation

    200 cGy, administered as part of the HSCT conditioning regimen

  • RituximabDrug

    Administered as part of the HSCT conditioning regimen

Study groups in NCT06986382
Study groupRoleWhat they receive
Cohort 1b: Safety Lead-InExperimentalAn initial cohort of 4 patients will be enrolled as part of the initial Phase 1b safety run-in evaluation. Patients will undergo an αβdepleted hematopoietic stem cell transplant (HSCT) after receiving a conditioning regimen.
Receives: Device: CliniMACS® TCR α/β Reagent Kit and CliniMACS® CD19 System; Drug: Prednisone/Methylprenisolone; Drug: Palifermin; Drug: ATG; Drug: Clofarabine; Drug: Melphalan; Radiation: Total Body Irradiation; Drug: Rituximab
Cohort 2aExperimentalIf the intervention is determined to be safe and non-futile, the study will continue to enroll 10 more patients under Phase 2a following the same treatment as Phase 1b.
Receives: Device: CliniMACS® TCR α/β Reagent Kit and CliniMACS® CD19 System; Drug: Prednisone/Methylprenisolone; Drug: Palifermin; Drug: ATG; Drug: Clofarabine; Drug: Melphalan; Radiation: Total Body Irradiation; Drug: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of patients with myeloid engraftment

    Cumulative incidence of donor myeloid engraftment by Day +42 post-HSCT. Myeloid engraftment is defined as ANC of > 0.5 x 109/L for three consecutive laboratory values obtained on different days. Date of myeloid engraftment is the first date of the three lab values taken.

    Measured: Day 42 post-HSCT

  2. Number of patients with Grade III-IV acute graft vs host disease (GVHD)

    Cumulative incidence of acute GvHD (graded as II-IV and III-IV using the Magic criteria)

    Cumulative incidence of acute GvHD (graded as II-IV and III-IV using the Magic criteria)

    Cumulative incidence of acute GvHD (graded as II-IV and III-IV using the Magic criteria)

    Cumulative incidence of acute GvHD (graded using the Magic criteria)

    Measured: Day 90 and 180 post-HSCT

  3. Number of patients in remission of Crohn disease (Calprotectin)

    Cumulative incidence of patient who achieve remission defined by fecal calprotectin values less than 250 mg/g

    Measured: 2 years post-HSCT

  4. Number of patients in remission of Crohn disease (wPCDAI or CDAI)

    Cumulative incidence of remission demonstrated by weighted Pediatric Crohn's Disease Activity Index (wPCDAI) <12.5 or Crohn's Disease Activity Index (CDAI) of <150 if adult

    Measured: 2 years post-HSCT

Secondary outcomes (11)

  1. Number of patients who achieve normal immune function derived from donor cells

    Cumulative incidence of patients with age-appropriate normalization of peripheral blood lymphocyte numbers including T, NK and B cells

    Measured: 1 year post-HSCT

  2. Number of patients who achieve full donor chimerism

    Cumulative incidence of patient chimerism defined as >95% of donor cells as assessed by peripheral blood (total, CD15+, CD3+, CD56+, CD19+, and CD34+) chimerism by short tandem repeat (STR) or next generation sequencing (NGS) analysis

    Measured: 1 year post-HSCT

  3. Number of patients with healthy immune cell function

    Cumulative incidence of patients who have mitogen and antigen specific T-cell proliferation or cytokine release in response to in vitro stimulation

    Measured: 1 year post-HSCT

  4. Number of patients who regain CD3 cells

    CD3 cell count of >200/ uL

    Measured: Day 90 and 180 post-HSCT

  5. Number of patients who experience moderate and severe chronic GvHD

    Cumulative incidence of patients experiencing moderate or severe chronic GvHD by NIH Consensus Criteria for Organ scoring of cGVHD

    Measured: 1 year post-HSCT

  6. Number of patients who experience severe infections

    Cumulative incidence of patients experiencing Grade 3 or higher CTCAE infections after HSCT

    Measured: 1 year post-HSCT

  7. Patient survival

    Measured: 2 and 5 years post-HSCT

  8. Number of patients with response in Crohn disease activity - 50% CRP or higher

    Cumulative incidence of patients who have a <0.5 mg/dL reduction in C-reactive protein (CRP)

    Measured: 1 and 2 years post-HSCT

  9. Number of patients with response in Crohn disease activity - wPCDAI/CDAI

    Cumulative incidence of patients who achieve wPCDAI score reduced by 17.5 points from baseline if pediatric, CDAI reduced by at least 100 points from baseline if adult

    Measured: 1 year post-HSCT

  10. Number of patients with endoscopic healing

    Endoscopic healing defined as ≤1 SEMA score

    Measured: 2 years post-HSCT

  11. Number of patients with sustained steroid-free remission

    Cumulative incidence of patients who are able to discontinue steroids for 3 or more months

    Measured: 2 years post-HSCT

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 May 2025
  2. Study startJul 2025 (estimated)
  3. Primary completionJul 2037 (estimated)
  4. Study completionJul 2040 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
14 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06986382
Sponsor's protocol ID
78920
Status last verified
May 2025
First submitted
20 May 2025
Last updated
23 May 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
No

Publications

  • Kammermeier J, Dziubak R, Pescarin M, Drury S, Godwin H, Reeve K, Chadokufa S, Huggett B, Sider S, James C, Acton N, Cernat E, Gasparetto M, Noble-Jamieson G, Kiparissi F, Elawad M, Beales PL, Sebire NJ, Gilmour K, Uhlig HH, Bacchelli C, Shah N. Phenotypic and Genotypic Characterisation of Inflammatory Bowel Disease Presenting Before the Age of 2 years. J Crohns Colitis. 2017 Jan;11(1):60-69. doi: 10.1093/ecco-jcc/jjw118. Epub 2016 Jun 14.

    PubMed 27302973

  • de Lange KM, Moutsianas L, Lee JC, Lamb CA, Luo Y, Kennedy NA, Jostins L, Rice DL, Gutierrez-Achury J, Ji SG, Heap G, Nimmo ER, Edwards C, Henderson P, Mowat C, Sanderson J, Satsangi J, Simmons A, Wilson DC, Tremelling M, Hart A, Mathew CG, Newman WG, Parkes M, Lees CW, Uhlig H, Hawkey C, Prescott NJ, Ahmad T, Mansfield JC, Anderson CA, Barrett JC. Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease. Nat Genet. 2017 Feb;49(2):256-261. doi: 10.1038/ng.3760. Epub 2017 Jan 9.

    PubMed 28067908

  • Graham DB, Xavier RJ. Pathway paradigms revealed from the genetics of inflammatory bowel disease. Nature. 2020 Feb;578(7796):527-539. doi: 10.1038/s41586-020-2025-2. Epub 2020 Feb 26.

    PubMed 32103191

  • Crowley E, Warner N, Pan J, Khalouei S, Elkadri A, Fiedler K, Foong J, Turinsky AL, Bronte-Tinkew D, Zhang S, Hu J, Tian D, Li D, Horowitz J, Siddiqui I, Upton J, Roifman CM, Church PC, Wall DA, Ramani AK, Kotlarz D, Klein C, Uhlig H, Snapper SB, Gonzaga-Jauregui C, Paterson AD, McGovern DPB, Brudno M, Walters TD, Griffiths AM, Muise AM. Prevalence and Clinical Features of Inflammatory Bowel Diseases Associated With Monogenic Variants, Identified by Whole-Exome Sequencing in 1000 Children at a Single Center. Gastroenterology. 2020 Jun;158(8):2208-2220. doi: 10.1053/j.gastro.2020.02.023. Epub 2020 Feb 19.

    PubMed 32084423

  • Cifaldi C, Chiriaco M, Di Matteo G, Di Cesare S, Alessia S, De Angelis P, Rea F, Angelino G, Pastore M, Ferradini V, Pagliara D, Cancrini C, Rossi P, Bertaina A, Finocchi A. Novel X-Linked Inhibitor of Apoptosis Mutation in Very Early-Onset Inflammatory Bowel Disease Child Successfully Treated with HLA-Haploidentical Hemapoietic Stem Cells Transplant after Removal of alphabeta+ T and B Cells. Front Immunol. 2017 Dec 22;8:1893. doi: 10.3389/fimmu.2017.01893. eCollection 2017.

    PubMed 29312354

  • Stiff PJ, Leinonen M, Kullenberg T, Rudebeck M, de Chateau M, Spielberger R. Long-Term Safety Outcomes in Patients with Hematological Malignancies Undergoing Autologous Hematopoietic Stem Cell Transplantation Treated with Palifermin to Prevent Oral Mucositis. Biol Blood Marrow Transplant. 2016 Jan;22(1):164-9. doi: 10.1016/j.bbmt.2015.08.018. Epub 2015 Aug 22.

    PubMed 26303102

  • Alatrash G, Thall PF, Valdez BC, Fox PS, Ning J, Garber HR, Janbey S, Worth LL, Popat U, Hosing C, Alousi AM, Kebriaei P, Shpall EJ, Jones RB, de Lima M, Rondon G, Chen J, Champlin RE, Andersson BS. Long-Term Outcomes after Treatment with Clofarabine +/- Fludarabine with Once-Daily Intravenous Busulfan as Pretransplant Conditioning Therapy for Advanced Myeloid Leukemia and Myelodysplastic Syndrome. Biol Blood Marrow Transplant. 2016 Oct;22(10):1792-1800. doi: 10.1016/j.bbmt.2016.06.023. Epub 2016 Jul 1.

    PubMed 27377901

  • Bertaina A, Grimm PC, Weinberg K, Parkman R, Kristovich KM, Barbarito G, Lippner E, Dhamdhere G, Ramachandran V, Spatz JM, Fathallah-Shaykh S, Atkinson TP, Al-Uzri A, Aubert G, van der Elst K, Green SG, Agarwal R, Slepicka PF, Shah AJ, Roncarolo MG, Gallo A, Concepcion W, Lewis DB. Sequential Stem Cell-Kidney Transplantation in Schimke Immuno-osseous Dysplasia. N Engl J Med. 2022 Jun 16;386(24):2295-2302. doi: 10.1056/NEJMoa2117028.

    PubMed 35704481

  • Greco R, Labopin M, Badoglio M, Veys P, Furtado Silva JM, Abinun M, Gualandi F, Bornhauser M, Ciceri F, Saccardi R, Lankester A, Alexander T, Gennery AR, Bader P, Farge D, Snowden JA. Allogeneic HSCT for Autoimmune Diseases: A Retrospective Study From the EBMT ADWP, IEWP, and PDWP Working Parties. Front Immunol. 2019 Jul 4;10:1570. doi: 10.3389/fimmu.2019.01570. eCollection 2019.

    PubMed 31333680

  • McLaughlin L, DeZoeten E, Verneris MR. Can allogeneic haematopoietic cell transplantation be curative in classical Crohn's disease? Br J Haematol. 2023 Mar;200(5):541-542. doi: 10.1111/bjh.18551. Epub 2022 Nov 9.

    PubMed 36352551

  • Moser LM, Fekadu J, Willasch A, Rettinger E, Sorensen J, Jarisch A, Kirwil M, Lieb A, Holzinger D, Calaminus G, Bader P, Bakhtiar S. Treatment of inborn errors of immunity patients with inflammatory bowel disease phenotype by allogeneic stem cell transplantation. Br J Haematol. 2023 Mar;200(5):595-607. doi: 10.1111/bjh.18497. Epub 2022 Oct 10.

    PubMed 36214981

  • Engelhardt KR, Shah N, Faizura-Yeop I, Kocacik Uygun DF, Frede N, Muise AM, Shteyer E, Filiz S, Chee R, Elawad M, Hartmann B, Arkwright PD, Dvorak C, Klein C, Puck JM, Grimbacher B, Glocker EO. Clinical outcome in IL-10- and IL-10 receptor-deficient patients with or without hematopoietic stem cell transplantation. J Allergy Clin Immunol. 2013 Mar;131(3):825-30. doi: 10.1016/j.jaci.2012.09.025. Epub 2012 Nov 14.

    PubMed 23158016

  • Lopez-Cubero SO, Sullivan KM, McDonald GB. Course of Crohn's disease after allogeneic marrow transplantation. Gastroenterology. 1998 Mar;114(3):433-40. doi: 10.1016/s0016-5085(98)70525-6.

    PubMed 9496932

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CliniMACS® TCR α/β Reagent Kit and CliniMACS® CD19 System, Prednisone/Methylprenisolone and Palifermin in people with Crohn Disease, run by Stanford University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 23 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of patients with myeloid engraftment (time frame: Day 42 post-HSCT). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06986382, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2025; AzTrials last refreshed its copy on 7 Nov 2026.

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