Recruiting
Phase 1
Phase 2

Allogeneic Stem Cell Transplantation

Sponsor:

Alice Bertaina

Code:

NCT05508009

Conditions

SIOD

Cystinosis

FSGS

SLE Nephritis

CKD Stage 4

Eligibility Criteria

Sex: All

Age: 1 - 30

Healthy Volunteers: Not accepted

Interventions

Cyclophosphamide 1200 mg/Kg

Fludarabine

Cyclophosphamide 100 mg/Kg

Total Body Irradiation

ATG

Study Details

Brief 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

Study ID

NCT05508009

Start date

Jan 10, 2023

Status verified date

Jul, 2023

Completion date

Oct, 2034

Anticipated

Primary completion date

Oct, 2032

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 1 - 30

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Anticipated need for kidney transplant due to:

a. Underlying genetic/immunologic disease the following conditions i. SIOD ii. FSGS iii. Cystinosis iv. SLE v. Membranoproliferative glomerulonephritis vi. Renal vasculitis characterized by positivity of the presence of ANCA vii. Other genetic diseases leading to kidney disease requiring KT Or b. Patients who have rejected a previous KT regardless of the underlying disease
  • Chronic kidney disease (CKD) stage 3 or greater
  • Steroids < 0.5 mg/Kg/day
  • The donor and recipient must be identical, as determined by high resolution typing, at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DQB1 and HLA-DRB1
  • Lansky/Karnofsky score > 50; the Karnofsky Scale will be used in subjects ≥ 16 years of age, and the Lansky Scale will be used for those < 16 years of age.
  • Able to give informed consent or have an LAR available to provide consent
  • Male and female subjects of childbearing potential must agree to use an effective means of birth control to avoid pregnancy throughout the transplant procedure, while on immunosuppression, and if the subject experiences any cGvHD

Exclusion Criteria:

  • Pregnant or lactating females.
  • Greater than Grade II aGvHD or severe, unmanaged extensive cGvHD due to a previous allograft at the time of inclusion
  • Dysfunction of liver (ALT/AST > 10 times upper normal value, or direct bilirubin > 3 times upper normal value), unmanageable dysfunction of renal function while undergoing dialysis
  • Severe cardiovascular disease at the time of evaluation unresponsive to nutritional and dialytic support (left ventricular ejection fraction < 40%), or clinical or echocardiographic evidence of severe diastolic dysfunction
  • Current active infectious disease. Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. Patients with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load.
  • Serious concurrent uncontrolled medical disorders except for primary disease leading to chronic kidney disease
  • Lack of patient/parent/guardian informed consent
  • Any severe concurrent disease which, in the judgement of the investigator would place the patient at increased risk during participation in the study

Study Design

Enrollment

12 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

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.

Interventions

Cyclophosphamide 1200 mg/Kg

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

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

Cyclophosphamide 100 mg/Kg

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

Total Body Irradiation

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

ATG

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

Rituximab

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

Melphalan

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

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

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

Primary outcome measure

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

Central Contacts and Locations

Locations

Lucile Packard Children's Hospital

Recruiting

Palo Alto, California, United States, 94305

Contacts

SCGT Clinical Trials Program

650-723-0912DL-SCTIntakeCoordinators@stanfordchildrens.org

Principal Investigator:

Alice Bertaina, MD

More Information

Sponsor

Alice Bertaina

Last update posted

Jul 17, 2023

Last verified

Jul, 2023

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Alice Bertaina on 2023-07-17.