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

Conditions

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

Eligibility Criteria

Sex

ALL

Age

1 Year - 30 Years

Healthy Volunteers

Not accepted

Interventions

• Cyclophosphamide 1200 mg/Kg — DRUG
  Cyclophosphamide 1200 mg/Kg will be administered as part of the conditioning regimen A prior to HSCT
• Fludarabine — DRUG
  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
• Cyclophosphamide 100 mg/Kg — DRUG
  Cyclophosphamide 100 mg/Kg will be administered as part of the conditioning regimen B prior to HSCT
• Total Body Irradiation — RADIATION
  Total Body Irradiation 200 cGy will be administered as part of the conditioning regimen prior to HSCT
• ATG — DRUG
  ATG 7.5 mg/Kg will be administered as part of the conditioning regimen prior to HSCT
• Rituximab — DRUG
  Rituximab 200 mg/m2 will be administered within 24 hours of the HSCT
• Melphalan — DRUG
  Melphalan 100 mg/m2 will be administered as part of the conditioning regimen prior to HSCT
• CliniMACS® TCR α/β Reagent Kit and CliniMACS® CD19 System — DEVICE
  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.
• Kidney Transplant — PROCEDURE
  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

Study Details

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.

Key Dates

Start date

Jan 10, 2023

Status verified

Jul 2023

Primary completion

Oct 31, 2032

Completion

Oct 31, 2034

Study Design

Enrollment

12 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Cohort 1b: Conditioning Regimen A
  An initial cohort of 4 patients will be enrolled as part of the initial Phase 1b safety run-in evaluation. Patients will undergo an αβdepleted hematopoietic stem cell transplant (HSCT) after receiving conditioning regimen A (conditioning regimen type is dependent on underlying disease and not part of the experimental goals). In the presence of donor myeloid engraftment, at least 3 months post-HSCT, patients will undergo a living donor kidney transplant (KT) using same donor as HSCT. In the absence of any clinical signs of kidney rejection, pharmacological immunosuppression (used for KT) will be tapered off by Day +90 post-KT.
• Experimental: Cohort 2a: Conditioning Regimen A
  If the intervention is determined to be safe and non-futile, the study will continue to enroll eight more patients under Phase 2a following the same treatment as Phase 1b.
• Experimental: Cohort 1b: Conditioning Regimen B
  An initial cohort of 4 patients will be enrolled as part of the initial Phase 1b safety run-in evaluation. Patients will undergo an αβdepleted hematopoietic stem cell transplant (HSCT) after receiving conditioning regimen B (conditioning regimen type is dependent on underlying disease and not part of the experimental goals). In the presence of donor myeloid engraftment, at least 3 months post-HSCT, patients will undergo a living donor kidney transplant (KT) using same donor as HSCT. In the absence of any clinical signs of kidney rejection, pharmacological immunosuppression (used for KT) will be tapered off by Day +90 post-KT.
• Experimental: Cohort 2a: Conditioning Regimen B
  If the intervention is determined to be safe and non-futile, the study will continue to enroll eight more patients under Phase 2a following the same treatment as Phase 1b.

Primary Outcome Measure

Number of patients who are able to discontinue immunosuppression post-KT [ Time Frame: Day +90 post-KT ]

Locations (1)

Find similar trials in Palo Alto, CA

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