The ONE Study ATDC Trial

Renal Failure, End Stage Clinical Trial

— ONEatDC  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02252055
• Other study ID #: RC13_0441
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 19, 2015
• Est. completion date: November 14, 2018

Study information

• Verified date: December 2018
• Source: Nantes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: November 14, 2018
• Est. primary completion date: November 14, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Kidney Failure, Chronic
• Renal Failure, End Stage
• Renal Insufficiency

Intervention

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)

Locations

Country	Name	City	State
France	Nantes University hospital	Nantes

Sponsors (1)

Lead Sponsor	Collaborator
Nantes University Hospital

Country where clinical trial is conducted

France, 

References & Publications (1)

Geissler EK. The ONE Study compares cell therapy products in organ transplantation: introduction to a review series on suppressive monocyte-derived cells. Transplant Res. 2012 Sep 28;1(1):11. doi: 10.1186/2047-1440-1-11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of malignancies arising directly from ATDC_Nantes		60 weeks
Other	ii) incidence of autoimmune disorders		60 weeks
Other	Incidence of inflammatory pathologies		60 weeks
Other	Incidence of anaemia, cytopaenia or biochemical disturbances unrelated to the function of the transplanted kidney.		60 weeks
Other	A Health-Economic Subproject will evaluate the health-related quality-of-life of trial patients using patient-reported outcome measures.	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.	60weeks
Primary	Incidence of biopsy-confirmed acute rejection (BCAR)		60 weeks
Secondary	Time to first acute rejection episode		60 weeks
Secondary	Severity of acute rejection episodes	based on response to treatment and histological scoring	60 weeks
Secondary	Total immunosuppressive burden	assessed at last study visit	60 weeks
Secondary	Incidence of patients treated for subclinical acute rejection on the basis of histopathological findings		60 weeks
Secondary	Prevention of chronic graft dysfunction (chronic rejection or IF/TA)	assessed by clinical (impairment of GFR) and histopathological (Banff staging) measures.	60 weeks
Secondary	Incidence of post-transplant dialysis, inclusion on the transplant waiting list or re-transplantation following graft loss through rejection (acute or chronic).		60 weeks
Secondary	Avoidance of drug-related complications by immunosuppressant reduction		60 weeks
Secondary	Incidence of embolic pulmonary complications and other embolic events		60 weeks
Secondary	Incidence of immunological reactions resulting in anaphylactoid reactions, immediate cardiovascular compromise or other acute organ failure		1 week
Secondary	Biochemical disturbances caused by cell infusion		1 week
Secondary	Over-suppression of the immune system assessed by the incidence of major and/or opportunistic infections, especially CMV, EBV and polyoma virus		1 week
Secondary	Over-suppression of the immune system assessed by the incidence of neoplasia.		1 week
Secondary	Immunological condition of study patients w	an extensive immune monitoring program has been established in the ONE Study	60 weeks

External Links

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