Actively Recruiting

Phase 1
Phase 2
Age: 1Year - 30Years
All Genders
ID05508009

Phase 1b/2a Trial of Allogeneic Hematopoietic Stem Cell Transplantation From an HLA-partially Matched Donor Followed by Kidney Transplant From the Same Donor in Patients Requiring Kidney Transplant

Led by Alice Bertaina · Updated on 2023-07-17

12

Participants Needed

1

Research Sites

104 weeks

Total Duration

On this page

Sponsors

A

Alice Bertaina

Lead Sponsor

C

California Institute for Regenerative Medicine (CIRM)

Collaborating Sponsor

AI-Summary

What this Trial Is About

Researchers are evaluating a phase 1b/2a trial studying sequential alpha-beta depleted hematopoietic stem cell transplantation (HSCT) and kidney transplantation (KT) in patients who need a kidney transplant. The goal is to prevent kidney rejection after transplant without lifelong immunosuppression, reducing the risk of chronic rejection and the need for repeated transplants. This trial is for patients with conditions such as SIOD, FSGS, cystinosis, SLE nephritis, or chronic kidney disease stage 4, among others. Participants will undergo one of two conditioning regimens prior to receiving alpha-beta depleted HSCT from a donor. At least three months after HSCT, if donor myeloid engraftment is confirmed and there are no signs of kidney rejection, patients will receive a living donor kidney transplant from the same donor. Pharmacological immunosuppression used for the kidney transplant will be tapered off by day 90 after the transplant if no rejection occurs. The study begins with a safety evaluation in a small group of patients and may expand based on safety and feasibility. During the study, patients will be closely monitored for donor cell engraftment, kidney function, and any signs of graft-versus-host disease (GvHD). Researchers will measure how many patients can stop immunosuppression by 90 days after kidney transplant, kidney function at one year, donor chimerism, and any acute or chronic GvHD. Follow-up will include assessments up to five years post-transplant to observe long-term outcomes such as secondary malignancies. Total participation length may extend up to a decade based on study timelines.

CONDITIONS

Brief Title

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

Who Can Participate

Age: 1Year - 30Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Anticipated need for kidney transplant due to underlying genetic or immunologic diseases such as SIOD, FSGS, cystinosis, SLE, membranoproliferative glomerulonephritis, renal vasculitis with ANCA positivity, other genetic diseases, or previous kidney transplant rejection
  • Chronic kidney disease stage 3 or greater
  • Steroid use less than 0.5 mg per kilogram per day
  • Donor and recipient must be identical for at least one allele of HLA-A, HLA-B, HLA-Cw, HLA-DQB1, and HLA-DRB1 by high resolution typing
  • Lansky or Karnofsky performance score greater than 50
  • Able to give informed consent or have a legally authorized representative to provide consent
  • Males and females of childbearing potential must agree to use effective birth control during transplant procedure, immunosuppression, and if chronic graft-versus-host disease occurs
Not Eligible

You will not qualify if you...

  • Pregnant or breastfeeding females
  • Greater than Grade II acute graft-versus-host disease or severe, unmanaged chronic graft-versus-host disease from previous transplant
  • Severe liver dysfunction (ALT/AST more than 10 times normal, or direct bilirubin more than 3 times normal)
  • Unmanageable renal dysfunction during dialysis
  • Severe cardiovascular disease unresponsive to support (ejection fraction less than 40% or severe diastolic dysfunction)
  • Active infectious disease, except controlled HIV, hepatitis B or cured hepatitis C as specified
  • Serious uncontrolled medical disorders other than primary kidney disease
  • Lack of informed consent
  • Any severe concurrent disease increasing risk during study participation as judged by investigator

AI-Screening

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Conditioning and Hematopoietic Stem Cell Transplantation (HSCT)

Duration - Up to 3 months

Participants receive a conditioning regimen including various chemotherapy drugs and radiation prior to undergoing an αβ-depleted hematopoietic stem cell transplant from an HLA-partially matched donor.

Multiple visits during conditioning and transplant period

Kidney Transplant

Duration - Day of transplant plus at least 3 months post-transplant for immunosuppression taper

In participants with successful donor cell engraftment and meeting eligibility criteria post-HSCT, a living donor kidney transplant is performed using the same donor as the HSCT.

1 transplant procedure and approximately weekly visits for 3 months post-transplant

Follow-up and Immunosuppression Taper

Duration - At least 3 months post-kidney transplant and up to 1 year or longer

Participants are monitored for kidney function, donor chimerism, graft-versus-host disease, and immunosuppression is tapered off if no rejection occurs.

Weekly to monthly visits during follow-up period

Trial Site Locations

Total: 1 location

1

Lucile Packard Children's Hospital

Palo Alto, California, United States, 94305

Actively Recruiting

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How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NON_RANDOMIZED

Model

SEQUENTIAL

Primary Purpose

TREATMENT

Number of Arms

4

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Published Research Related To This Trial

Long-term results in recipients of combined HLA-mismatched kidney and bone marrow transplantation without maintenance immunosuppression.

T Kawai, D H Sachs, B Sprangers...

https://pubmed.ncbi.nlm.nih.gov/24903438

Bayesian Hodges-Lehmann tests for statistical equivalence in the two-sample setting: Power analysis, type I error rates and equivalence boundary selection in biomedical research.

Riko Kelter

https://pubmed.ncbi.nlm.nih.gov/34404344

Analyses of the short- and long-term graft survival after kidney transplantation in Europe between 1986 and 2015.

Maarten Coemans, Caner Süsal, Bernd Döhler...

https://pubmed.ncbi.nlm.nih.gov/30049474