Donor-Alloantigen-Reactive Regulatory T Cell (darTreg) Therapy in Renal Transplantation (The ONE Study )

Official Title:

Donor-Alloantigen-Reactive Regulatory T Cell (darTreg) Therapy in Renal Transplantation: A ONE Study Clinical Trial

Basic Trial Information

Phase Type Age Sponsor Protocol IDs Status
Phase 1 Interventional 18 - 70 Years University of California, San Francisco ONEdarTreg14
NCT02244801
Enrolling patients

Study Design:


Principal Investigator

Associate Professor of Surgery
Division of Transplant Surgery
Surgical Director, Intestinal Rehabilitation and Transplantation

Clinical Research Coordinator

UCSF Medical Center at Parnassus
(415) 514-0192 Phone

Trial Summary

This Phase I pilot study will evaluate the safety, and tolerability of darTreg infusion for adult, de novo, living donor renal transplant recipients.

Eligibility

Inclusion Criteria: (organ donor eligibility)

     1. Eligible for live kidney donation
     2. At least 18 years of age
     3. An ABO blood type compatible with the organ recipient
     4. Willing and able to provide a blood sample for The ONE Study IM (Immune Monitoring)
         Subproject
     5. Willing to provide personal and medical/biological data for the trial analysis
     6. Eligible to give blood for B cell source prior to organ donation
     7. Signed and dated written informed consent*. *For subjects unable to read and/or
         write, oral informed consent observed by an independent witness is acceptable if the
         subject has fully understood oral information given by the Investigator. The witness
         should sign the consent form on behalf of the subject.
In signing the donor information sheet/informed consent form (DIS/ICF), organ donors agree
to undergo phlebotomy to provide donor B cells for the production of darTreg, to provide a
blood sample for the IM Subproject, and permit access to their medical records for the
collection of specified demographic and medical/biological data for the trial.
Organ Recipient eligibility:
A prospective kidney transplant recipient is eligible for enrollment into the study if all
of the following inclusion criteria apply:

     1. Chronic renal insufficiency necessitating kidney transplantation and approved to
         receive a primary kidney allograft from a living donor
     2. At least 18 years of age
     3. Able to commence the immunosuppressive regimen at the protocol-specified time point
     4. Willing and able to participate in The ONE Study IM and HEC (Health-Economics
         Subproject) subprojects
     5. Adequate venous access to support leukapheresis
     6. Signed and dated written informed consent*.
    - For patients unable to read and/or write, oral informed consent observed by an
       independent witness is acceptable if the patient has fully understood oral
       information given by the Investigator. The witness should sign the consent form
       on behalf of the patient.
Exclusion Criteria: (organ donor)
If a prospective donor fulfills any of the following criteria, they are ineligible for the
trial:

     1. Genetically identical to the prospective organ recipient at the HLA (human leukocyte
         antigen) loci (0-0-0 mismatch)
     2. CMV-positive and donating to a CMV-negative recipient
     3. Exposure to any investigational agents at the time of kidney donation, or within 28
         days prior to kidney donation
     4. Any form of substance abuse, psychiatric disorder, or other condition that, in the
         opinion of the Investigator, may invalidate communication with the Investigator
         and/or designated study personnel
     5. Subjects unable to freely give their informed consent (e.g. individuals under legal
         guardianship).
Exclusion criteria (organ recipient)

     1. Patient has previously received any tissue or organ transplant other than the planned
         kidney graft
     2. Known contraindication to the protocol-specified treatments / medications
     3. Genetically identical to the prospective organ donor at the HLA (human leukocyte
         antigen) loci (0-0-0 mismatch)
     4. PRA (panel reactive antibody) grade > 40% within 6 months prior to enrollment
     5. Previous treatment with any desensitization procedure (with or without IVIg)
     6. Concomitant malignancy or history of malignancy within 5 years prior to planned study
         entry (excluding successfully-treated non-metastatic basal/squamous cell carcinoma of
         the skin)
     7. Evidence of significant local or systemic infection
     8. HIV-positive, EBV-negative or suffering chronic viral hepatitis
     9. CMV-negative and receiving a kidney from a CMV-positive donor
     10. Significant liver disease, defined as persistently elevated AST (aspartate
         aminotransferase) and/or ALT(alanine aminotransferase) levels > 2 x ULN (Upper Limit
         of Normal range)
     11. Malignant or pre-malignant hematological conditions
     12. Neutrophils < 1000/μl ; platelets < 100,000/μl
     13. Regulatory T cells present in peripheral blood at <30/µL
     14. Any uncontrolled medical condition or concurrent disease that could interfere with
         the study objectives
     15. Any condition which, in the judgment of the Investigator, would place the subject at
         undue risk
     16. Ongoing treatment with systemic immunosuppressive drugs at study entry
     17. Patients who have received anti-T cell therapy within 30 days prior to transplant
         surgery
     18. Participation in another clinical trial during the study or within 28 days prior to
         planned study entry
     19. Female patients of reproductive potential with a positive pregnancy test at
         enrollment
     20. Female patients who are breast-feeding
     21. All female patients of reproductive potential* UNLESS the patient is willing to use
         an acceptable birth control for the duration of the study unless the patient chooses
         abstinence (she chooses to avoid heterosexual intercourse completely) (See Table 2.
         Acceptable Contraception Methods for Females of Reproductive Potential)
     22. Male patients unwilling to use a reliable and effective form of contraception for 3
         months after darTreg dosing
     23. Psychological, familial, sociological or geographical factors potentially hampering
         compliance with the study protocol and follow-up visit schedule
     24. Any form of substance abuse, psychiatric disorder, or other condition that, in the
         opinion of the Investigator, may invalidate communication with the Investigator
         and/or designated study personnel
     25. Patients unable to freely give their informed consent (e.g. individuals under legal
         guardianship).
    - Females of reproductive potential include girls who have entered puberty and all
       women who have a uterus and have not passed through menopause. Menopause is the
       permanent end of menstruation and fertility. Menopause should be clinically
       confirmed by a patient's healthcare practitioner. Some commonly used diagnostic
       criteria include 1) 12 months of spontaneous amenorrhea (not amenorrhea induced
       by a medical condition or medical therapy) or 2) postsurgical from a bilateral
       oophorectomy.
Exclusion Criteria B (organ recipient)
Below are exclusion criteria to be assessed post-transplantation and prior to darTreg
infusion. Subjects who meet any of these criteria should not receive a darTreg-infusion:

     1. Unacceptable darTreg product.
     2. Delayed graft function (requiring dialysis post-transplant).
     3. Requiring oxygen supplementation to keep capillary oxygen saturations >95%.
     4. Any medical or technical complications (e.g. myocardial infarction, urine leak, wound
         dehiscence, pneumonia, ongoing fevers, etc.) that in the judgment of the
         investigators or responsible clinician would put the subject at undue risk.-

Detailed Description

A single-center, open-label, dose-escalation pilot trial of a single infusion of darTregs in
two dosing cohorts. This study is an independent single-center clinical trial. However, the
organizational and mechanistic infrastructure of the study will be provided by the ONE Study
project, a European Union funded collaborative project, whose objective is to assess
distinct purified hematopoietic immunoregulatory cells as clinical therapies in solid organ
transplantation. This study is one of multiple clinical trials within the framework of The
ONE Study project, based on the same general design.

Important

Final eligibility is determined by the health professionals conducting the trial and the protocol approved by the Committee on Human Resources (CHR) at the University of California, San Francisco (UCSF). The Patient Consent Form for this trial is available upon request. For more information about this trial, please see the full posting at ClinicalTrials.gov.

Information about this trial was obtained from the NIH Clinical Trials website, http://clinicaltrials.gov on 2/7/2017. UCSF specific information including the PI (Principal Investigator), trial enrollment status, and UCSF Study ID, supplement the ClinicalTrials.gov study posting.
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