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

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.

Timeline

Start

2025-07

Primary completion

2037-07

Completion

2040-07

Publications

• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.

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Indications