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Kidney TransplantPhase 1NCT06056102

CAR-T Cell Therapy for Desensitization in Kidney Transplantation

A Phase 1 study testing Cyclophosphamide, CART-BCMA and huCART19 in people with Kidney Transplant and Kidney Failure, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Cyclophosphamide, CART-BCMA and huCART19
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
3 sitesUnited States
Study dates
9 May 2024to 15 Dec 2042
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female patients aged 18-65 years with kidney failure requiring hemodialysis.
  • Patients must meet one of the following two criteria:
  • All the following:
  • Protocol-specific cPRA ≥99.5%
  • No suitable living donor OR has been active in a kidney paired donation program but not received a match within 12 months
  • Have blood group Type O or B, and predictive of a positive virtual crossmatch to an available deceased donor.
Show all 19Show fewer
  • United Network for Organ Sharing (UNOS) listed for kidney transplant for at least 1 year
  • 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
  • Platelet count ≥120,000/μL

Who cannot join

  • 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)
  • Subjects described in exclusion #4 with structural disease such as polycystic kidney disease, obstructive uropathy with nephrolithiasis or those otherwise at higher risk of urinary tract infections. Anuric subjects with structural kidney disease are not excluded
  • 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
Show all 35Show fewer
  • 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 >5mg/day, intravenous immunoglobulin, cyclophosphamide, tacrolimus, mycophenolic acid, or azathioprine from 30 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 Systemic Lupus Erythematosus that has been managed with a stable low dose of prednisone (5mg or less for at least 8 weeks) without other immunosuppressants or targeted biologics; or 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.
  • Moderate-severe pulmonary function abnormality, defined as resting oxygen saturation <92% on room air or FEV1, TLC, or DLCO (after correction for hemoglobin) <50% of predicted values
  • Patients who have received any live vaccine within 30 days of planned leukapheresis
  • Treatment with any investigational agent within 4 weeks (or 5 half-lives of investigational drug, whichever is longer) of screening
  • Pregnant, currently breastfeeding, or planning to become pregnant during the primary or post-transplant follow up of the study.
  • Past or current social or medical problems; or findings from physical examination or laboratory testing that are not listed above, which in the opinion of investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study
  • Lymphodepleting Chemotherapy Eligibility:
  • Study entry eligibility must be re-assessed prior to starting lymphodepletion. In addition, subjects must undergo respiratory viral testing on nasal or nasopharyngeal swabs (per institutional practice) for SARS-CoV-2 and influenza within 7 days prior to the first planned lymphodepletion chemotherapy.
  • If the subject is positive for influenza, Tamiflu® or equivalent should be administered per package insert. The subject must complete treatment and symptoms must be improving and either resolved or nearly resolved in the judgment of the treating investigator prior to receiving lymphodepleting chemotherapy and CAR T cells. Repeat influenza testing is not required prior to initiating lymphodepleting chemotherapy and CAR T cell infusion.
  • If the subject tests positive for SARS-CoV-2, the subject will be managed per institutional practice. Subject will be eligible to initiate lymphodepleting chemotherapy and CAR T cell infusion once cleared from requirement for isolation according to institutional and/or CDC guidance.
  • If testing is positive for another respiratory virus (e.g., as part of a multiplex respiratory pathogen panel in the course of testing for influenza or SARS-CoV-2), the lymphodepleting chemotherapy and CAR T cell infusion will be delayed for at least 7 days to be sure clinical symptoms of a viral infection do not develop. If clinical symptoms develop, the lymphodepleting chemotherapy and CAR T cell infusion will be delayed until resolution of these symptoms.
  • CAR T Cell Infusion Eligibility:
  • The criteria below will be assessed by the investigator following lymphodepleting chemotherapy and before administration of CAR T cells. Subjects who do not satisfy these criteria may have CAR T cell infusion delayed until such time as criteria are satisfied. Subjects who receive lymphodepleting chemotherapy but in whom CAR T cell infusion is delayed >4 weeks after the first day of lymphodepleting chemotherapy will receive a second cycle of lymphodepleting chemotherapy prior to CAR T cell infusion. For subjects receiving fludarabine, a second cycle of cyclophosphamide can be administered, but fludarabine will not be repeated.
  • Subjects must not have developed deterioration in performance status or overall clinical condition or new laboratory abnormalities that would, in the opinion of the treating investigator, render it unsafe to proceed with CAR T cell infusion. The following are specific conditions that warrant delaying CAR T cell infusion:
  • Requirement for supplemental oxygen to maintain peripheral oxygen saturation ≥95%.
  • Presence of clinically significant radiographic abnormalities on chest x-ray. Chest x-ray is not required to evaluate for radiographic abnormalities in the absence of suggestive symptoms or exam findings.
  • New cardiac arrhythmia not controlled with medical management. EKG is not required to evaluate for arrhythmia in the absence of suggestive symptoms or exam findings.
  • Hypotension requiring vasopressor support.
  • Active infection: Diagnostic test results indicating new bacterial, fungal, or viral infection within prior 48 hours.
  • Subjects must have adhered to restrictions on pre-infusion therapy.

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Mary Kaminski, PA contact

215-349-8334

mary.kaminski@pennmedicine.upenn.edu

United States3 sites, 3 recruiting

  • Massachusetts General Hospital: Transplantation (Site #: 71107)

    Boston, Massachusetts, 02114

    Sydney Guthrie-Baker, 617-643-4179, sguthrie-baker@mgh.harvard.edu

    Recruiting

  • NYU Langone Health (Site #: 71177)

    New York, New York, 10016

    Kathryn Dzurilla, 347-802-5853, Kathryn.Dzurilla@nyulangone.org

    Recruiting

  • University of Pennsylvania Medical Center (Site #: 71111)

    Philadelphia, Pennsylvania, 19104

    Mary Kaminski, 215-349-8334, Mary.Kaminski@pennmedicine.upenn.edu

    Recruiting

Other trials in United States

About this study

Official title: Autologous Chimeric Antigen Receptor Engineered T Cell Immunotherapy for Desensitization in Patients Awaiting Kidney Transplantation

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.

Read the detailed description

CTOT-46 will enroll up to up to 26 highly sensitized kidney transplant candidates at 3 centers. There will be a safety run-in and 2 treatment cohorts to assess the safety and pharmacodynamics of CART-BCMA and huCART-19.

Following screening and enrollment, the subject will undergo leukapheresis to collect T cells for CAR T cell manufacturing. Subsequently, subjects will undergo lymphodepleting chemotherapy followed by CART-BCMA and huCART19 cell infusions. A secondary objective is to evaluate the efficacy of study treatment to reduce cPRA and determine the duration cPRA reduction.

Being tested
Cyclophosphamide, CART-BCMA, huCART19
Keywords
Kidney transplant, CART-BCMA, huCART-19, Highly sensitized, cPRA, UNOS waiting list, End stage renal failure patients with cPRA >99.5%
Medical subject headings
Renal Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Also called Cytoxan

    • 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

  • CART-BCMABiological

    Also called Chimeric Antigen Receptor T cell (CART)/B cell maturation antigen (BCMA)

    • 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

  • huCART19Biological

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

    • 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
Study groups in NCT06056102
Study groupRoleWhat they receive
Participant CohortsExperimental* Safety Run-in phase (2 subjects at UPenn) * Cohort 1 (3-12 subjects) * Cohort 2 (3-12 subjects)
Receives: Drug: Cyclophosphamide; Biological: CART-BCMA; Biological: huCART19

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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 (≥600/microL for those with Duffy null associated phenotype) and Platelets >75,000/microL at 60 days after first CART cell infusion
    4. Dose limiting toxicity

    Measured: 12 months after infusion of CART-BCMA with huCART-19

  2. 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 (≥600/microL for those with Duffy null associated phenotype) and Platelets >75,000/microL at 60 days after first CART cell infusion
    4. Dose limiting toxicity

    Measured: 12 months after infusion of CART-BCMA with huCART-19

  3. 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 (≥600/microL for those with Duffy null associated phenotype) and Platelets >75,000/microL at 60 days after first CART cell infusion
    4. Dose limiting toxicity

    Measured: 12 months after infusion of CART-BCMA with huCART-19

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

    Measured: From time of lymphodepletion to 12 months

Secondary outcomes (4)

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

    Measured: 26 weeks after the infusion

  2. Duration of Calculated Panel Reactive Antibody (cPRA) response

    Measured: From time of infusion to 12 months

  3. 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

    Measured: 3 years after transplantation

  4. The proportion of subjects with opportunistic infections

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Sep 2023
  2. Study start9 May 2024
  3. Primary completion15 Dec 2028 (estimated)
  4. Study completion15 Dec 2042 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06056102
Sponsor's protocol ID
DAIT CTOT-46
Status last verified
Sep 2026
First submitted
20 Sep 2023
Last updated
8 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Bhoj VG, Kaminski M, Zhao H, Jackson K, Wang W, Liu C, Montgomery RA, Ali N, Mangiola M, Spitzer TR, Safa K, Pattanayak V, Taj R, Chiu J, Bui TM, Sonnenberg EM, Markmann JF, Milone MC, June CH, Siegel DL, Fraietta JA, Gonzalez V, Locci M, Palmer M, Monos D, Hwang WT, Sledge T, Bridges ND, Goldstein JS, Odim J, Sweet SC, Besharatian BD, Hussain SM, Brown NK, Kamoun M, Garfall AL, Naji A. Kidney Transplantation in Two Highly Sensitized Candidates after CAR T-Cell Therapy. N Engl J Med. 2026 Jun 4;394(21):2117-2125. doi: 10.1056/NEJMoa2513428.

    PubMed 42235014

  • 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.

    PubMed 38995690

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cyclophosphamide, CART-BCMA and huCART19 in people with Kidney Transplant and Kidney Failure, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 8 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Mary Kaminski, PA (215-349-8334, mary.kaminski@pennmedicine.upenn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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) (time frame: 12 months after infusion of CART-BCMA with huCART-19). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06056102, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2026.

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