NCT05508009

Early Trial of Allogeneic Hematopoietic Stem Cell Transplantation for Patients Who Will Receive a Kidney Transplant From the Same Donor

Phase 1b/2a Trial of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) From an HLA-partially Matched Related or Unrelated Donor After TCRαβ+ T-cell/CD19+ B-cell Depletion for Patients Who Will Receive a Kidney Transplant (KT) From the Same HSCT/KT Donor

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 12 (estimated)
• Sponsor: Alice Bertaina · Academic / Other
• Sex: All
• Age: 1 Year – 30 Years
• Healthy volunteers: Not accepted

Summary

This is a single center, non-randomized, non-controlled open-label phase 1b/2a trial of performing sequential αβdepleted-HSCT and KT in patients requiring KT to prevent kidney rejection post-KT, in the absence of any post-KT immunosuppression, to abrogate the need for lifelong immunosuppression, the risk of chronic rejection and, ultimately, the need for repeated transplantation.

Conditions

• SIOD
• Cystinosis
• FSGS
• SLE Nephritis
• CKD Stage 4

Interventions

Type	Name	Description
DRUG	Cyclophosphamide 1200 mg/Kg	Cyclophosphamide 1200 mg/Kg will be administered as part of the conditioning regimen A prior to HSCT
DRUG	Fludarabine	Fludarabine (starting dose 0.5 mg/Kg and then PK guided to reach an AUC of 18-20) will be administered as part of the conditioning regimen prior to HSCT
DRUG	Cyclophosphamide 100 mg/Kg	Cyclophosphamide 100 mg/Kg will be administered as part of the conditioning regimen B prior to HSCT
RADIATION	Total Body Irradiation	Total Body Irradiation 200 cGy will be administered as part of the conditioning regimen prior to HSCT
DRUG	ATG	ATG 7.5 mg/Kg will be administered as part of the conditioning regimen prior to HSCT
DRUG	Rituximab	Rituximab 200 mg/m2 will be administered within 24 hours of the HSCT
DRUG	Melphalan	Melphalan 100 mg/m2 will be administered as part of the conditioning regimen prior to HSCT
DEVICE	CliniMACS® 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.
PROCEDURE	Kidney Transplant	In the presence of donor myeloid engraftment, at least 3 months post-HSCT, with \> 95% donor CD3+ chimerism, in the absence of signs of active aGvHD or cGvHD (moderate or severe), at least 4 weeks off of immunosuppression for any previously occurring acute or chronic GvHD (except single agent treatment of mild cGvHD), and with a BMI \>18.5, ambulatory and active in addition to the eligibility for the standard of care KT criteria, patients will undergo a living donor KT using same donor as HSCT

Timeline

• Start date: 2023-01-10
• Primary completion: 2032-10-01
• Completion: 2034-10-01
• First posted: 2022-08-19
• Last updated: 2023-07-17

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated device study