Clinical trial NCT05508009: Early Trial of Allogeneic Hematopoietic Stem Cell Transplantation for Patients Who Will Receive a Kidney Transplant From the Same Donor
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: SIOD
Cystinosis
FSGS
SLE Nephritis
CKD Stage 4
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: California Institute for Regenerative Medicine (CIRM)
First posted: 2022-08-19
Enrollment: 12
Sex: ALL
Minimum age (years): 1
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The study has two cohorts (Cohort 1b which will be safety lead-in with 4 patients, and then cohort 2a of 8 patients). The data generated will be compared with historical data available on outcomes of KT performed as SoC in this patient population.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of patients who are able to discontinue immunosuppression post-KT
timeFrame: Day +90 post-KT
Secondary outcomes:
measure: Number of patients with successful kidney function
timeFrame: +1 year post-KT
measure: Number of patients with myloid engraftment
timeFrame: Day +42 post-HSCT
measure: Number of patients with persistent full donor chimerism
timeFrame: Day +180 and 1 year post-KT
measure: Number of patients with acute GvHD
timeFrame: Day +90 and Day +180 post-HSCT
measure: Number of patients with chronic GvHD
timeFrame: +1 year post-HSCT
measure: Number of patients with de novo acute GVHD
timeFrame: +1 year post-KT
measure: Number of patients with de novo chronic GVHD
timeFrame: +1 year post-KT
measure: Number of patients with functional tolerance to donor cells
timeFrame: 6- and 12-months post-KT
measure: Number of cases of secondary malignancies
timeFrame: +5 year post-KT
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital
state: California
Study officials:
affiliation: Stanford University
name: Alice Bertaina, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Paul Grimm, MD
role: PRINCIPAL_INVESTIGATOR
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