Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

The ONE Study ATDC Trial (ONEatDC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02252055
Recruitment Status : Completed
First Posted : September 29, 2014
Last Update Posted : January 2, 2019
Sponsor:
Information provided by (Responsible Party):
Nantes University Hospital

Brief Summary:
To collect evidence of the safety of administering autologous tolerogenic dendritic cells (ATDC) preparations to living-donor renal transplant recipients in the context of an international European Union funded consortium aimed at evaluationg cellular immunotherapy in solid organ transplantation (The ONE Study). It is anticipated that immune regulation induced by ATDC therapy can evntually be used to reduce the need for conventional immunosuppression in transplant recipients.

Condition or disease Intervention/treatment Phase
Renal Failure, End Stage Biological: ATDC_Nantes Phase 1 Phase 2

Detailed Description:
Decades of immunosuppressive drug development have produced an array of powerful pharmacological agents, but the various drawbacks associated with these treatments leaves considerable room for improvement. By harnessing the power of suppressive mechanisms in the human immune system, regulatory cell therapy may be able to support peripheral tolerance and induce a level of donor-specific unresponsiveness that allows for a reduction in the use of conventional immunosuppression in organ transplant recipients. Several alternative regulatory cell types have been identified as potential adjunct immunotherapies for solid organ transplantation and are now approaching a stage of development that would allow clinical testing in an early-stage trial. The ONE Study aims to answer the question as whether ATDC treatment, or immunoregulatory cell-based therapy in general, has any place in the clinical management of solid organ transplant recipients.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Monocentric Trial of Cellular Immunotherapy Based on Autologous Tolerogenic Dendritic Cells (ATDCs) Administration in Patients With Renal Insufficiency Receiving as First Transplantation a Kidney Transplant From a Living-donor.
Actual Study Start Date : March 19, 2015
Actual Primary Completion Date : November 14, 2018
Actual Study Completion Date : November 14, 2018

Arm Intervention/treatment
Experimental: ATDC Treatment

ATDC treatment (1 x 106 cells/kg BW slow peripheral venous) occurs the day before transplantation.

Recipients also receive prednisolone, Mycophenolate Mofetil and tacrolimus, as detailed below :

Prednidolone :

  • D 0: 500 mg IV
  • D 1: 125 mg IV
  • D 2 to 14: 20.0 mg/d
  • Wk 3 to 4: 15.0 mg/d
  • Wk 5 to 8: 10.0 mg/d
  • Wk 9 to 12: 5.0 mg/d
  • Wk 13 to 14: 2.5 mg/d
  • Wk 15 to End:Cessation

MMF (or biologic equiv.):

  • D -7 to -2: 500 mg/d (250mg 2x/d)
  • D -1 to 14: 2000 mg/d
  • Wk 3 to 36: 1000 mg/d
  • Wk 37 to 40: 750 mg/d
  • Wk 41 to 44: 500 mg/d
  • Wk 45 to 48: 250 mg/d
  • Wk 49 to End:Cessation Note : MMF tapering will only happen if the 36-week protocol biopsy shows no signs of subclinical rejection and there is evidence of declining renal function or if the clinician has any other concern about MMF dose reduction.

Tacrolimus :

  • ≤ 48 h pre-Tx to D 14: 3-12 ng/ml
  • Wk 3 to 12: 3-10 ng/ml
  • Wk 13 to 36: 3-8 ng/ml
  • Wk 37 to End: 3-6 ng/ml
Biological: ATDC_Nantes

ATDC treatment (1 x 106 cells/kg BW slow peripheral venous) occurs the day before transplantation into recipients also recipients of a living donor renal transplantation.

Recipients also receive prednisolone, Mycophenolate Mofetil and tacrolimus background immunosuppression ( as described in detail in the arm description)





Primary Outcome Measures :
  1. Incidence of biopsy-confirmed acute rejection (BCAR) [ Time Frame: 60 weeks ]

Secondary Outcome Measures :
  1. Time to first acute rejection episode [ Time Frame: 60 weeks ]
  2. Severity of acute rejection episodes [ Time Frame: 60 weeks ]
    based on response to treatment and histological scoring

  3. Total immunosuppressive burden [ Time Frame: 60 weeks ]
    assessed at last study visit

  4. Incidence of patients treated for subclinical acute rejection on the basis of histopathological findings [ Time Frame: 60 weeks ]
  5. Prevention of chronic graft dysfunction (chronic rejection or IF/TA) [ Time Frame: 60 weeks ]
    assessed by clinical (impairment of GFR) and histopathological (Banff staging) measures.

  6. Incidence of post-transplant dialysis, inclusion on the transplant waiting list or re-transplantation following graft loss through rejection (acute or chronic). [ Time Frame: 60 weeks ]
  7. Avoidance of drug-related complications by immunosuppressant reduction [ Time Frame: 60 weeks ]
  8. Incidence of embolic pulmonary complications and other embolic events [ Time Frame: 60 weeks ]
  9. Incidence of immunological reactions resulting in anaphylactoid reactions, immediate cardiovascular compromise or other acute organ failure [ Time Frame: 1 week ]
  10. Biochemical disturbances caused by cell infusion [ Time Frame: 1 week ]
  11. Over-suppression of the immune system assessed by the incidence of major and/or opportunistic infections, especially CMV, EBV and polyoma virus [ Time Frame: 1 week ]
  12. Over-suppression of the immune system assessed by the incidence of neoplasia. [ Time Frame: 1 week ]
  13. Immunological condition of study patients w [ Time Frame: 60 weeks ]
    an extensive immune monitoring program has been established in the ONE Study


Other Outcome Measures:
  1. Incidence of malignancies arising directly from ATDC_Nantes [ Time Frame: 60 weeks ]
  2. ii) incidence of autoimmune disorders [ Time Frame: 60 weeks ]
  3. Incidence of inflammatory pathologies [ Time Frame: 60 weeks ]
  4. Incidence of anaemia, cytopaenia or biochemical disturbances unrelated to the function of the transplanted kidney. [ Time Frame: 60 weeks ]
  5. A Health-Economic Subproject will evaluate the health-related quality-of-life of trial patients using patient-reported outcome measures. [ Time Frame: 60weeks ]
    This subproject will also calculate the cost-effectiveness of ATDC_Nantes to review the financial implications of cellular immunotherapy as a practical and routine clinical prescription.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

RECIPIENT

Inclusion Criteria:

  1. Chronic renal insufficiency necessitating kidney transplantation and approved to receive a primary kidney allograft from a living donor
  2. Aged at least 18 years
  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 subprojects
  5. Eligible for leucapheresis prior to organ transplantation
  6. Signed and dated written informed consent

Exclusion Criteria:

  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 (like known allergies to heparin)
  3. Genetically identical to the prospective organ donor at the HLA loci (A.B.DR 0 mismatch)
  4. PRA grade > 0 within 6 months prior to enrolment
  5. Previous treatment with any desensitisation 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. ABO incompatibility
  8. Presence of DSA (donor specific antibodies) detected by luminex prior transplantation
  9. Evidence of significant local or systemic infection
  10. HIV-positive, EBV-negative or suffering chronic viral hepatitis, syphilis serology- positive
  11. Significant liver disease, defined as persistently elevated AST and/or ALT levels > 2 x ULN (Upper Limit of Normal range)
  12. Malignant or pre-malignant haematological conditions
  13. Any uncontrolled medical condition or concurrent disease that could interfere with the study objectives
  14. Any condition which, in the judgement of the Investigator, would place the subject at undue risk
  15. Ongoing treatment with systemic immunosuppressive drugs at inclusion (despite corticoids lower than 10 mg)
  16. Participation in another clinical trial during the study or within 28 days prior to planned study entry
  17. Exposure to an investigational product during the study or within 28 days prior to planned study entry
  18. Female patients of child-bearing potential with a positive pregnancy test at enrolment and F01
  19. Female patients who are breast-feeding
  20. All female patients of child-bearing potential* UNLESS:

    1. The patient is willing to maintain a highly effective method of birth control** for the duration of the study
    2. The career, lifestyle, or sexual orientation of the patient ensures that there is no risk of pregnancy for the duration of the study (at the discretion of the Investigator)
  21. Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up visit schedule
  22. 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
  23. Patients unable to freely give their informed consent (e.g. individuals under legal guardianship).

    Criteria specific to the infusion of the ATDC_Nantes:

  24. Any pro-coagulant disposition, as evidenced by a past history of thromboembolic disease or abnormal laboratory coagulation parameters which, in the judgement of the Investigator, would place the subject at undue risk
  25. Any condition resulting in a substantial reduction in the volume of the pulmonary vasculature or an increase in the pulmonary vascular resistance. Any disease or disease process leading to substantially elevated pulmonary arterial pressure (as evidenced by electrocardiography, echocardiography, radiology or cardiac catheterisation) or right heart hypertrophy or dysfunction
  26. Known atrial or ventricular septal defects posing a risk of paradoxical embolism of infused cells or cell aggregates
  27. Known hypersensitivity to any component of the cell product or components used in the manufacture of the cell product.

DONOR

Inclusion Criteria:

  1. Eligible for live kidney donation
  2. Willing and able to provide a blood sample for The ONE Study IM Subproject
  3. Willing to provide personal and medical/biological data for the trial analysis
  4. Signed and dated written informed consent

Exclusion Criteria:

  1. Genetically identical to the prospective organ recipient at the HLA loci (A.B.DR 0 mismatch)
  2. Exposure to any investigational agents at the time of kidney donation, or within 28 days prior to kidney donation
  3. 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
  4. Subjects unable to freely give their informed consent (e.g. individuals under legal guardianship).
  5. ABO incompatibility

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02252055


Locations
Layout table for location information
France
Nantes University hospital
Nantes, France, 44093
Sponsors and Collaborators
Nantes University Hospital
Investigators
Layout table for investigator information
Study Director: Edward K Geissler, PhD University Hospital Regensburg
Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Nantes University Hospital
ClinicalTrials.gov Identifier: NCT02252055    
Other Study ID Numbers: RC13_0441
First Posted: September 29, 2014    Key Record Dates
Last Update Posted: January 2, 2019
Last Verified: December 2018
Additional relevant MeSH terms:
Layout table for MeSH terms
Kidney Failure, Chronic
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Renal Insufficiency, Chronic