CAR-T Cell Therapy for Desensitization in Kidney Transplantation

NCT06056102 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: DAIT CTOT-46
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is for people who have been waiting for a kidney transplant for at least one year, and who have a cPRA of 99.5% or higher. Having a cPRA of 99.5% or higher means that your immune system would reject 99.5% of kidneys available for transplant. The study will test whether new products called Chimeric Antigen Receptor T Cells (CAR T Cells), when given with chemotherapy, is safe and will reduce cPRA. The main study will last up to 2 years: Participants will have up to 30 clinic or hospital visits over a one-year period. If a transplant takes place, there will be 9 more visits after transplant. Long term follow up is required by the Food and Drug Administration (FDA) for 15 years after receiving CAR T cell. The primary objective is to evaluate the safety and feasibility of administering CART BCMA + huCART-19 following lymphodepletion, including determination of optimal tolerated regimen (OTR) and/or recommended phase 2 regimen, according to the incidence of dose limiting toxicity (DLT) in highly sensitized patients awaiting kidney transplant.

Conditions

Kidney Transplant; Kidney Failure; End Stage Renal Failure on Dialysis

Keywords

Kidney transplant; CART-BCMA; huCART-19; Highly sensitized; cPRA; UNOS waiting list; End stage renal failure patients with cPRA >99.5%

Outcome Measures

Primary Outcomes (4)

• The timing of adverse events after infusion of Chimeric antigen receptor T - B cell maturation antigen (CART-BCMA) with CD19 Targeted Humanized CAR T Cell (huCART-19)

  Adverse events will be categorized and described according to CTCAE v5.0. Specific safety outcomes will include but are not limited to: 1. Cytokine release syndrome, as defined by American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading 2. Neurotoxicity (ICANS), as defined by ASTCT consensus grading 3. Delayed hematopoetic recovery: proportion of subjects achieving ANC \>1,000/microL and Platelets \>75,000/microL at 60 days after first CART cell infusion 4. Dose limiting toxicity

  From time of lymphodepletion to 12 months

• The frequency of adverse events after infusion of Chimeric antigen receptor T - B cell maturation antigen (CART-BCMA) with CD19 Targeted Humanized CAR T Cell (huCART-19)

  Adverse events will be categorized and described according to CTCAE v5.0. Specific safety outcomes will include but are not limited to: 1. Cytokine release syndrome, as defined by ASTCT consensus grading 2. Neurotoxicity (ICANS), as defined by ASTCT consensus grading 3. Delayed hematopoetic recovery: proportion of subjects achieving ANC \>1,000/microL and Platelets \>75,000/microL at 60 days after first CART cell infusion 4. Dose limiting toxicity

  From time of lymphodepletion to 12 months

• The severity of adverse events after infusion of Chimeric antigen receptor T - B cell maturation antigen (CART-BCMA) with CD19 Targeted Humanized CAR T Cell (huCART-19)

  Adverse events will be categorized and described according to CTCAE v5.0. Specific safety outcomes will include but are not limited to: 1. Cytokine release syndrome, as defined by ASTCT consensus grading 2. Neurotoxicity (ICANS), as defined by ASTCT consensus grading 3. Delayed hematopoetic recovery: proportion of subjects achieving ANC \>1,000/microL and Platelets \>75,000/microL at 60 days after first CART cell infusion 4. Dose limiting toxicity

  From time of lymphodepletion to 12 months

• The proportion of apheresed subjects who receive the intended/planned Chimeric antigen receptor T (CAR T) cell dose in the respective cohort

  From time of lymphodepletion to 12 months

Secondary Outcomes (4)

• The proportion of subjects meeting the predefined Calculated Panel Reactive Antibody (cPRA) reduction criteria after the infusion of CART-BCMA + huCART-19

  26 weeks after the infusion

• Duration of Calculated Panel Reactive Antibody (cPRA) response

  From time of infusion to 12 months

• For subjects who are transplanted, the proportion of subjects experiencing acute cellular rejection or antibody mediated rejection, delayed graft function (as well as AKI), graft loss OR De Novo donor specific antibody

  3 years after transplantation

• The proportion of subjects with opportunistic infections

  From time of infusion to 12 months or 3 years after transplantation

Study Arms (1)

Participant Cohorts

EXPERIMENTAL

* Safety Run-in phase (2 subjects at UPenn) * Cohort 1 (3-6 subjects) * Cohort 2 (3-6 subjects) * Cohort 3 (3-6 subjects)

Drug: Cyclophosphamide; Biological: CART-BCMA; Biological: huCART19; Drug: Fludarabine

Interventions

Cyclophosphamide DRUG

* Safety Run-in: 375mg/m\^2 daily x 3 * Cohort 1: 375mg/m\^2 daily x 3 * Cohort 2: 375mg/m\^2 daily x 3 * Cohort 3: 375mg/m\^2 daily x 3

Also known as: Cytoxan

Participant Cohorts

CART-BCMA BIOLOGICAL

* Safety Run-in: 5 x 10\^7 CAR T cells * Cohort 1: 1.5 x 10\^8 CAR T cells * Cohort 2: 1.5 x 10\^8 CAR T cells * Cohort 3: 5 x 10\^8 CAR T cells

Also known as: Chimeric Antigen Receptor T cell (CART)/B cell maturation antigen (BCMA)

Participant Cohorts

huCART19 BIOLOGICAL

* Safety Run-in: 5 x 10\^7 CAR T cells * Cohort 1: 1.5 x 10\^8 CAR T cells * Cohort 2: 1.5 x 10\^8 CAR T cells * Cohort 3: 5 x 10\^8 CAR T cells

Also known as: Chimeric Antigen Receptor T cell (CART)/ CD-19 Targeted Humanized CAR T Cell

Participant Cohorts

Fludarabine DRUG

• Cohort 3: 24mg/m\^2 daily x 3

Also known as: Fludara

Participant Cohorts

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged 18-65 years with kidney failure requiring hemodialysis.
• United Network for Organ Sharing (UNOS) listed for kidney transplant for at least 1 year.
• Patients must meet one of the following two criteria:
• Protocol-specific cPRA ≥99.5-99.895% AND no matched living donor, ineligible for kidney paired donation programs, have blood group Type O or B, have documentation of virtual crossmatch (current or past) and predictive of a positive physical crossmatch to a deceased donor
• Protocol-specific cPRA ≥99.9% Protocol-specific cPRA must be rounded from three significant figures measured ≤90 days from the time of enrollment (i.e., cPRA of 0.994500 or 0.998500 would be eligible) using the web-based OPTN cPRA calculator (https://optn.transplant.hrsa.gov/resources/allocation-calculators/cpra-calculator/); accounting for HLA-A, -B, -C, -DRB1, -DRB3/4/5, and -DQB1 Luminex Single Antigen Beads (SAB) with MFI ≥3000; 1 archived sample within 6 months of screening required.
• Based on center-specific listing policies, a cPRA in UNet Waitlist that is ≥99.5% (the candidate must be eligible for additional priority of kidneys equivalent to individuals with a 100% cPRA)
• Able to understand and give written informed consent to participate in all aspects of the study.
• Willing to stay within 2 hours of the home study site for at least 28 days after the last T cell infusion
• Subjects of reproductive potential must agree to use contraception for at least one year after CAR T Cell infusion
• In the absence of contraindication, vaccinations must be up to date per the DAIT Guidance for Patients in Transplant Trials and include TdAP
• Positive for EBV capsid IgG
• Negative testing for latent TB infection within 3 months prior to enrollment. Testing should be conducted using either a PPD or interferon-gamma release assay (i.e. QuantiFERON-TB, T-SPOT.TB). Patients with a positive test for latent TB infection must complete appropriate therapy for Latent Tuberculosis Infection (LTBI). A subject is considered eligible only if they have a negative test for LTBI within 3 months prior to enrollment OR they have appropriately completed LTBI therapy prior to transplant. Latent TB infection treatment regimens should be among those endorsed by the CDC
• Hemoglobin ≥9g/dL
• ANC ≥ 1,800/μL, \> 1,200/ μL for patients with Duffy-null associated neutrophil count (DANC)
• Absolute Lymphocyte Counts ≥500/μL or CD3 T cell Count ≥150/μL

You may not qualify if:

• Subjects with indwelling catheters as primary access for hemodialysis
• Previous solid organ (except kidney) or bone marrow transplant
• BMI ≥35 kg/m\^2
• Subjects who have preserved or oliguric urine output \> 100 cc/day with history of recurrent UTI (2 in 6 months or 3 in 1 year, see study definitions)
• Known active current or history of invasive fungal infection; any non-tuberculous mycobacterial infection that has been active or has required therapy within the last year. Any infection requiring hospitalization and IV antibiotics within 4 weeks of screening or PO antibiotics within 2 weeks
• History of HIV, chronic HBV, or chronic HCV, regardless of treatment
• Negative CMV serology
• Detectible viral load HBV, HCV, CMV, EBV, or BK by PCR
• Any B cell depleting or monoclonal antibody therapy within 6 months prior to enrollment
• Receiving ongoing immunosuppression including corticosteroids, intravenous immunoglobulin, cyclophosphamide, tacrolimus, mycophenolic acid, or azathioprine from 90 days prior to study entry
• Active auto-immune disease, including connective tissue disease, uveitis, sarcoidosis, inflammatory bowel disease, or multiple sclerosis, or have a history of severe (as judged by the investigator) autoimmune disease requiring prolonged immunosuppressive therapy, except for renal-limited autoimmune conditions without risk for systemic manifestations (e.g. IgA nephropathy)
• Any chronic illness requiring uninterrupted anti-coagulation or anti-platelet therapy
• History of cirrhosis or severe liver disease, including abnormal liver profile (aspartate aminotransferase \[AST\], alanine aminotransferases \[ALT\] or total bilirubin \> 3 times upper limit of normal at screening (except for patients in whom hyperbilirubinemia is attributed to Gilbert's syndrome)
• History of sickle cell disease, or systemic amyloidosis
• Cardiac clearance for transplant \> 6 months old and/or any of the following: NYHA Class III or IV heart failure, unstable angina, left ventricular ejection fraction \< 40%, a history of recent (within 6 months) myocardial infarction or implantable cardioverter/ defibrillators and/or biventricular pacing.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• University of Pennsylvania Clinical Cell and Vaccine Production Facility (CVPF): collaborator

Study Sites (3)

Massachusetts General Hospital: Transplantation (Site #: 71107)

Boston, Massachusetts, 02114, United States

RECRUITING

NYU Langone Health (Site #: 71177)

New York, New York, 10016, United States

RECRUITING

University of Pennsylvania Medical Center (Site #: 71111)

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Related Publications (1)

• Vo A, Ammerman N, Jordan SC. New Therapies for Highly Sensitized Patients on the Waiting List. Kidney360. 2024 Aug 1;5(8):1207-1225. doi: 10.34067/KID.0000000000000509. Epub 2024 Jul 12.

  PMID: 38995690 DERIVED

MeSH Terms

Conditions

Renal Insufficiency

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Vijay Bhoj, M.D., Ph.D.

  University of Pennsylvania Medical Center: Transplantation

  STUDY CHAIR

• Ali Naji, MD, Ph.D.

  University of Pennsylvania Medical Center: Transplantation

  PRINCIPAL INVESTIGATOR

• Alfred Garfall, MD

  University of Pennsylvania Medical Center: Transplantation

  STUDY CHAIR

Central Study Contacts

Mary Kaminski, PA

CONTACT

215-349-8334; mary.kaminski@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2023
• First Posted: September 28, 2023
• Study Start: May 9, 2024
• Primary Completion (Estimated): December 15, 2028
• Study Completion (Estimated): December 15, 2042
• Last Updated: November 26, 2025

Record last verified: 2025-11

Locations

US (3)