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Status unknownNCT01408797DAWNUpdated Aug 22, 2011

Clonal Deletion on Living-Relative Donor Kidney Transplantation

A Phase 1/2 interventional study of donor specific transfusion and MMF, Bortezomib in Renal Transplantation and Uremia, sponsored by Fuzhou General Hospital. Status unknown at 1 site in China. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2011-08-22.

Sponsored by Fuzhou General Hospital · Phase 1/2, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Feb 2011), so the status shown — last known as Recruiting — may be out of date.
Phase
Phase 1/2
Study type
Interventional
Enrollment
15
Allocation
Non-randomized
Ages
18 Years to 60 Years
Sex
All
01

Study summary

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.

Read the 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.

02

Conditions studied

  • Renal Transplantation
  • Uremia

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Keywords

  • clonal deletion
  • kidney transplantation
03

Who can participate

Ages eligible
18 Years to 60 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
15 participants (estimated)

Study arms

  • Experimental
    Donor specific transfusion

    Subjects with uremia will undergo donor specific transfusion before transplantation

    Procedure: donor specific transfusion

  • Experimental
    Clonal deletion

    Drug: MMF, Bortezomib

  • Experimental
    Drugs Added When Needed

    Procedure: drugs added according to the immuno condition of the recipients

Interventions

  • Proceduredonor specific transfusion

    before transplantation,200mL of donor whole blood will be transfused to the recipient

  • DrugMMF, Bortezomib

    MMF and Bortezomib will be administered after donor specific transfusion

  • Proceduredrugs 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

05

What researchers measure

Primary outcomes

  1. Dosage of immunosuppressants

    Effectiveness of clonal deletion on reducing the dosage of immunosuppressants (calcineurin inhibitor plus mycophenolate, azothioprine, or sirolimus).

    Time frame: one year

Secondary outcomes

  1. immune event

    Time to immune event (acute rejection or DSA);

    Time frame: 1 year

  2. DSA

    Proportion of patients who become positive for donor specific HLA antibodies post transplant

    Time frame: 1 year

  3. DGF

    Incidence of delayed graft function (defined as need for post-transplant dialysis)

    Time frame: 1 years

  4. Renal function

    Change in renal function as determined by estimated glomerular filtration rate and proteinuria (\>1g) at 1 year post transplant

    Time frame: 1 year

  5. Survival

    Allograft Survival at 1 year post transplant

    Time frame: 1 year

06

Study locations

1 of 1 sites recruiting
  • No. 156, Xi er huan Road
    Fuzhou, Fujian 350025, China
    • Tan Jianming, MD,PhD · Contact · doctortjm@yahoo.com · 8613375918000
    • Gao Xia, MD · Contact · gaojxia@yahoo.com.cn · 8615959165311
    • Tan Jianming, MD,PhD · Principal investigator
    • Gao Xia, MD · Principal investigator
    Recruiting
07

Registry details

Key details

Study ID
NCT01408797
Lead sponsor
Fuzhou General Hospital
Collaborators
Terasaki Foundation
First posted
Aug 3, 2011
Start date
Mar 2011
Primary completion
Mar 2013 (estimated)
Completion
Mar 2013 (estimated)
Last update
Aug 22, 2011

Study contacts

Tan Jianming, MD,PhD
Contact
doctortjm@yahoo.com
8613375918000
Gao Xia, MD
Contact
gaojxia@yahoo.com.cn
8615959165311
Tan Jianming, MD,PhD
principal investigator · Fuzhou General Hospital

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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This study is status unknown, as verified in Feb 2011. You cannot join it, but the record below documents what was studied.

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