Clonal Deletion on Living-Relative Donor Kidney Transplantation (DAWN)
Recruitment status was Recruiting
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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 |
- 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).
- 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 |
Inclusion Criteria:
- Uremia patient of any race that is greater than or equal to 18 years of age but less than 60 years old
- Recipients of a kidney from a certifiable relative donor 18-60 years of age
- 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:
- 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
- Patient with prior solid organ transplant or cell transplant (e.g. bone marrow or islet cell).
- 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
- Patient receiving a concurrent SOT (heart, liver, pancreas) or cell transplant (islet, bone marrow, stem cell)
- ABO incompatible donor recipient pair or CDC crossmatch positive transplant
- 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
- Donor with cardiac death (non-heart beating donor)
- Recipient CMV seronegative receiving a organ from a seropositive donor (CMV seromismatch)
- Donor OR Recipient are known hepatitis C antibody-positive or polymerase chain reaction (PCR) positive for hepatitis C
- Donors OR Recipient are known hepatitis B surface antigen-positive or PCR positive for hepatitis B AND recipient is HBV negative
- Patient and/or donors with known human immunodeficiency virus (HIV) infection
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)
- Patient with any significant infection or other contraindication that would preclude transplant
- Patient with a history of hypercoaguable state
- 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.
- Patient with active peptic ulcer disease (PUD), chronic diarrhea, or gastrointestinal malabsorption
- Patient with a history of cancer within the last 5 years (exception: non-melanoma skin cell cancers cured by local resection are permitted)
- Patient with a chest radiograph (no more than 2 months prior to randomization) consistent with an acute lung parenchymal process and malignancy
- Patient with a hypersensitivity to any study drugs
- Patient who have used any investigational drug within 30 days prior to the Day 1 visit
- . 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
- Prisoner or patient compulsorily detained (involuntarily incarcerated) for treatment or either a psychiatric or physical (e.g. infectious disease) illness
Contacts and Locations| Contact: Tan Jianming, MD,PhD | 8613375918000 | doctortjm@yahoo.com |
| Contact: Gao Xia, MD | 8615959165311 | gaojxia@yahoo.com.cn |
| 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 | |
| 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 May 21, 2013