Clinical trial NCT01656135: Reference Group Trial for The ONE Study
Official title: Reference Group Trial for The ONE Study: A Unified Approach to Evaluating Cellular Immunotherapy in Solid Organ Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: End-stage Renal Failure
Kidney Graft Rejection
Keywords: gold standard treatment
immune monitoring
acute rejection
graft rejection
living-donor
renal transplantation
kidney transplantation
Lead sponsor: University of Regensburg
Sponsor class: OTHER
Collaborators: name: European Commission
First posted: 2012-08-02
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: To investigate the progression of the immunological response in living-donor kidney transplant recipients treated with a standard immunosuppressive regimen. Clinical, immunological, and health-economic data collected during this Reference Group Trial will be used to corroborate historical renal transplantation statistics and generate reference ranges for future clinical studies that will test immunoregulatory cell therapy as an adjunct immunosuppressive treatment in renal transplantation.


Eligibility criteria: Inclusion Criteria:

Organ Donor:

A prospective donor is eligible for the research if all of the following inclusion criteria apply:

1. Eligible for live kidney donation
2. Aged at least 18 years
3. An ABO blood type compatible with the organ recipient
4. Willing and able to provide a blood sample for The ONE Study Subprojects
5. Willing to provide personal and medical/biological data for the trial
6. Signed and dated written informed consent.

In signing the donor information sheet/informed consent form (DIS/ICF), organ donors agree 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:

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 subprojects
5. Signed and dated written informed consent.

Exclusion Criteria:

Organ Donor:

If a prospective donor fulfils any of the following criteria, then they are ineligible for the trial:

1. Genetically identical to the prospective organ recipient at the HLA loci
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).

Organ Recipient:

1. Patient has previously received, or is scheduled to receive, any tissue or organ transplant other than the planned kidney graft
2. Known sensitivity to tacrolimus, mycophenolate, or corticosteroids
3. Genetically identical to the prospective organ donor at the HLA loci
4. PRA grade \> 40% 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. Evidence of significant local or systemic infection
8. HIV-positive, EBV-negative or suffering chronic viral hepatitis
9. Significant liver disease, defined as persistently elevated AST and/or ALT levels \>2 x ULN (Upper Limit of Normal range)
10. Malignant or pre-malignant haematological conditions
11. Any uncontrolled medical condition or concurrent disease that could interfere with the study objectives
12. Any condition which, in the judgement of the Investigator, would place the subject at undue risk
13. Ongoing treatment with systemic immunosuppressive drugs at study entry
14. Participation in another clinical trial during the study or within 28 days prior to planned study entry
15. Female patients of child-bearing potential with a positive pregnancy test at enrolment
16. Female patients who are breast-feeding
17. 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 local Investigator)
18. Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up visit schedule
19. 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
20. Patients unable to freely give their informed consent (e.g. individuals under legal guardianship).

Primary outcomes:
measure: biopsy-confirmed acute rejection incidence
timeFrame: 60 weeks
Secondary outcomes:
measure: time to first acute rejection episode
timeFrame: within 60 weeks
measure: severity of acute rejection episodes
timeFrame: within 60 weeks
measure: total immunosuppressive burden
timeFrame: 60 weeks
measure: incidence of chronic graft dysfunction
timeFrame: 60 weeks
measure: incidence of graft loss through rejection
timeFrame: 60 weeks
measure: incidence of adverse drug reactions
timeFrame: 60 weeks
measure: incidence of major infections
timeFrame: 60 weeks
measure: incidence of neoplasia
timeFrame: 60 weeks
measure: incidence of patients treated for subclinical acute rejection
timeFrame: 60 weeks
Other outcomes:
measure: Immune Monitoring (IM) assessment
timeFrame: 60 weeks
measure: Health Economics (HEC) assessment
timeFrame: 60 weeks
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Nantes
country: France
facility: CHU de Nantes Hotel-Dieu
city: Berlin
country: Germany
facility: Charite Campus Virchow-Klinikum
city: Regensburg
country: Germany
facility: University Hospital Regensburg
city: Milan
country: Italy
facility: Ospedale San Raffaele
city: London
country: United Kingdom
facility: Guy's Hospital in affiliation with King's College London
city: Oxford
country: United Kingdom
facility: Churchill Hospital in affiliation with the University of Oxford
Study officials:
affiliation: University of Regensburg
name: Edward K. Geissler, Ph.D.
role: STUDY_DIRECTOR
References:
citation: Sawitzki B, Harden PN, Reinke P, Moreau A, Hutchinson JA, Game DS, Tang Q, Guinan EC, Battaglia M, Burlingham WJ, Roberts ISD, Streitz M, Josien R, Boger CA, Scotta C, Markmann JF, Hester JL, Juerchott K, Braudeau C, James B, Contreras-Ruiz L, van der Net JB, Bergler T, Caldara R, Petchey W, Edinger M, Dupas N, Kapinsky M, Mutzbauer I, Otto NM, Ollinger R, Hernandez-Fuentes MP, Issa F, Ahrens N, Meyenberg C, Karitzky S, Kunzendorf U, Knechtle SJ, Grinyo J, Morris PJ, Brent L, Bushell A, Turka LA, Bluestone JA, Lechler RI, Schlitt HJ, Cuturi MC, Schlickeiser S, Friend PJ, Miloud T, Scheffold A, Secchi A, Crisalli K, Kang SM, Hilton R, Banas B, Blancho G, Volk HD, Lombardi G, Wood KJ, Geissler EK. Regulatory cell therapy in kidney transplantation (The ONE Study): a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials. Lancet. 2020 May 23;395(10237):1627-1639. doi: 10.1016/S0140-6736(20)30167-7.