RecruitingPhase 1Phase 2NCT05508009

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

Sponsor

Alice Bertaina

Enrollment

12 participants

Start Date

Jan 10, 2023

Study Type

INTERVENTIONAL

Conditions

Cystinosis CKD Stage 4 FSGS SIOD SLE Nephritis

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.

Eligibility

Min Age: 1 YearMax Age: 30 Years

Plain Language Summary

Simplified for easier understanding

This study is testing whether giving a bone marrow stem cell transplant before a kidney transplant (from the same donor) can help the body accept the kidney without needing lifelong immunosuppressive drugs. This approach, called tolerance induction, may benefit patients with certain genetic or immune kidney diseases who need a transplant. You may be eligible if: - You are between 1 and 30 years old - You need a kidney transplant due to a genetic or immune kidney disease, or because a previous transplant failed - You have stage 3 or greater chronic kidney disease - Your donor matches you at key immune markers (HLA) - Your performance score is above 50 You may NOT be eligible if: - You are pregnant or breastfeeding - You have severe heart, liver, or other organ dysfunction - You have active, uncontrolled infection (unless HIV or hepatitis with undetectable viral load on treatment) - You have had Grade II or higher severe graft-versus-host disease from a prior transplant Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGCyclophosphamide 1200 mg/Kg

Cyclophosphamide 1200 mg/Kg will be administered as part of the conditioning regimen A prior to HSCT

DRUGFludarabine

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

DRUGCyclophosphamide 100 mg/Kg

Cyclophosphamide 100 mg/Kg will be administered as part of the conditioning regimen B prior to HSCT

RADIATIONTotal Body Irradiation

Total Body Irradiation 200 cGy will be administered as part of the conditioning regimen prior to HSCT

DRUGATG

ATG 7.5 mg/Kg will be administered as part of the conditioning regimen prior to HSCT

DRUGRituximab

Rituximab 200 mg/m2 will be administered within 24 hours of the HSCT

DRUGMelphalan

Melphalan 100 mg/m2 will be administered as part of the conditioning regimen prior to HSCT

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.

PROCEDUREKidney 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