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)
Stanford University
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.
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 range
- 2–30 years
- Sex
- All
- Healthy volunteers
- No
Recipient 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 e…
Interventions
- DeviceCliniMACS® TCR α/β Reagent Kit and CliniMACS® CD19 System
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.
- DrugPrednisone/Methylprenisolone
Administered as part of the HSCT conditioning regimen
- DrugPalifermin
Administered as part of the HSCT conditioning regimen
- DrugATG
Administered as part of the HSCT conditioning regimen
- DrugClofarabine
Administered as part of the HSCT conditioning regimen
- Drug
Location
- Lucile Packard Children's HospitalPalo Alto, California