Clonal Deletion on Living-Relative Donor Kidney Transplantation (DAWN)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2011 by Fuzhou General Hospital.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Terasaki Foundation
Information provided by:
Fuzhou General Hospital
ClinicalTrials.gov Identifier:
NCT01408797
First received: August 2, 2011
Last updated: August 19, 2011
Last verified: February 2011
  Purpose

The objective of this trial is to determine if clonal deletion before kidney transplantation can effectively reduce the need for post transplant immunosuppression. The investigators will adapt a DAWN (Drugs (immunosuppressants) Added When Needed) treatment protocol to assess the effect of clonal deletion and closely monitor acute rejection, renal function, and graft survival. 15 patients eligible for the study as described below will be enrolled.


Condition Intervention Phase
Renal Transplantation
Uremia
Procedure: donor specific transfusion
Drug: MMF, Bortezomib
Procedure: drugs added according to the immuno condition of the recipients
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective, Open-Label, Pilot Study of Clonal Deletion on Living-Relative Donor Kidney Transplantation

Resource links provided by NLM:


Further study details as provided by Fuzhou General Hospital:

Primary Outcome Measures:
  • Dosage of immunosuppressants [ Time Frame: one year ] [ Designated as safety issue: No ]
    Effectiveness of clonal deletion on reducing the dosage of immunosuppressants (calcineurin inhibitor plus mycophenolate, azothioprine, or sirolimus).


Secondary Outcome Measures:
  • immune event [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Time to immune event (acute rejection or DSA);

  • DSA [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Proportion of patients who become positive for donor specific HLA antibodies post transplant

  • DGF [ Time Frame: 1 years ] [ Designated as safety issue: Yes ]
    Incidence of delayed graft function (defined as need for post-transplant dialysis)

  • Renal function [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Change in renal function as determined by estimated glomerular filtration rate and proteinuria (>1g) at 1 year post transplant

  • Survival [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Allograft Survival at 1 year post transplant


Estimated Enrollment: 15
Study Start Date: March 2011
Estimated Study Completion Date: March 2013
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Donor specific transfusion
Subjects with uremia will undergo donor specific transfusion before transplantation
Procedure: donor specific transfusion
before transplantation,200mL of donor whole blood will be transfused to the recipient
Experimental: Clonal deletion Drug: MMF, Bortezomib
MMF and Bortezomib will be administered after donor specific transfusion
Experimental: Drugs Added When Needed Procedure: drugs added according to the immuno condition of the recipients
drugs (corticosteroid, MMF and/or CNI) will be added according to the recipients immuno event and donor specific antibody

Detailed Description:

The objective of this trial is to determine if clonal deletion can effectively reduce the need for post transplant immunosuppressive medicine. Emphasis will be placed on adverse events that are associated with clonal deletion. The investigators will assess whether DAWN (Drugs (immunosuppressants) Added When Needed) is feasible in living-relative donor kidney transplantation and the effectiveness of clonal deletion treatment on the rate of rejection, patient survival, and graft function from day 0 to 12 months after transplantation. Numbers of patients on single drug and dual therapy immunosuppression will be counted. Additionally, the investigators would assess time to immune event (rejection or antibody), the severity of acute rejection or antibody mediated rejection by Banff criteria, the incidence of delayed graft function (defined as the need for post-transplant dialysis), and the incidence of adverse events including infection, grade 3 and above non-hematologic toxicities, and grade 4 hematologic toxicities.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Uremia patient of any race that is greater than or equal to 18 years of age but less than 60 years old
  2. Recipients of a kidney from a certifiable relative donor 18-60 years of age
  3. Patient is willing and capable of giving written informed consent for study participation and able to participate in the study for 12 months

Exclusion Criteria:

  1. Women who are pregnant, intend to become pregnant in the next 1 years, breastfeeding, or have a positive pregnancy test on enrollment or prior to study medication administration
  2. Patient with prior solid organ transplant or cell transplant (e.g. bone marrow or islet cell).
  3. Patient is deemed likely to have a second solid organ transplant or cell transplant (e.g. bone marrow or islet cell) in next 3 years
  4. Patient receiving a concurrent SOT (heart, liver, pancreas) or cell transplant (islet, bone marrow, stem cell)
  5. ABO incompatible donor recipient pair or CDC crossmatch positive transplant
  6. Sensitized patients (most recent anti-HLA Class I or II Panel Reactive Antibodies (PRA)>0% by a CDC-assay) or patients identified a high immunological risk by the transplant physician
  7. Donor with cardiac death (non-heart beating donor)
  8. Recipient CMV seronegative receiving a organ from a seropositive donor (CMV seromismatch)
  9. Donor OR Recipient are known hepatitis C antibody-positive or polymerase chain reaction (PCR) positive for hepatitis C
  10. Donors OR Recipient are known hepatitis B surface antigen-positive or PCR positive for hepatitis B AND recipient is HBV negative
  11. Patient and/or donors with known human immunodeficiency virus (HIV) infection
  12. Patient at risk for tuberculosis (TB) Current clinical, radiographic, or laboratory evidence of active or latent TB as determined by local standard of care

    History of active TB:

    Within the last 2 years, even if treated Greater than 2 years ago, unless there is documentation of adequate treatment according to locally accepted clinical practice Patient at risk of reactivation of TB precludes administration of conventional immunosuppression (as determined by investigator and based upon appropriate evaluation)

  13. Patient with any significant infection or other contraindication that would preclude transplant
  14. Patient with a history of hypercoaguable state
  15. Patient with a history of substance abuse (drugs or alcohol) within the past 6 months, or psychotic disorders that are not compatible with adequate study follow-up.
  16. Patient with active peptic ulcer disease (PUD), chronic diarrhea, or gastrointestinal malabsorption
  17. Patient with a history of cancer within the last 5 years (exception: non-melanoma skin cell cancers cured by local resection are permitted)
  18. Patient with a chest radiograph (no more than 2 months prior to randomization) consistent with an acute lung parenchymal process and malignancy
  19. Patient with a hypersensitivity to any study drugs
  20. Patient who have used any investigational drug within 30 days prior to the Day 1 visit
  21. . Patients with autoimmune disease or patient treated with immunosuppressive therapy (eg methotrexate, abatacept, etc) for indications such as autoimmune disease or patient with comorbidity to a degree that treatment with such agents is likely during the trial
  22. Prisoner or patient compulsorily detained (involuntarily incarcerated) for treatment or either a psychiatric or physical (e.g. infectious disease) illness
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01408797

Contacts
Contact: Tan Jianming, MD,PhD 8613375918000 doctortjm@yahoo.com
Contact: Gao Xia, MD 8615959165311 gaojxia@yahoo.com.cn

Locations
China, Fujian
No. 156, Xi er huan Road Recruiting
Fuzhou, Fujian, China, 350025
Contact: Tan Jianming, MD,PhD    8613375918000    doctortjm@yahoo.com   
Contact: Gao Xia, MD    8615959165311    gaojxia@yahoo.com.cn   
Principal Investigator: Tan Jianming, MD,PhD         
Principal Investigator: Gao Xia, MD         
Sponsors and Collaborators
Fuzhou General Hospital
Terasaki Foundation
Investigators
Principal Investigator: Tan Jianming, MD,PhD Fuzhou General Hospital
  More Information

No publications provided

Responsible Party: Fuzhou General Hospital, Tan Jianming, MD,PhD
ClinicalTrials.gov Identifier: NCT01408797     History of Changes
Other Study ID Numbers: DAWN-2011-TJM
Study First Received: August 2, 2011
Last Updated: August 19, 2011
Health Authority: China:Fujian Province branch of Food and Drug Administration

Keywords provided by Fuzhou General Hospital:
clonal deletion
kidney transplantation

Additional relevant MeSH terms:
Uremia
Kidney Diseases
Urologic Diseases
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2014