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

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

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

Sponsors & Collaborators

• California Institute for Regenerative Medicine (CIRM)

  collaborator OTHER

• Alice Bertaina

  lead OTHER

Principal Investigators

• Alice Bertaina, MD · Stanford University

• Paul Grimm, MD · Stanford University

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

1 Year

Max Age

30 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-01-10

Primary Completion

2032-10-31

Completion

2034-10-31

FDA Device

Yes

Countries

• United States

Study Locations