Clonal Deletion on Living-Relative Donor Kidney Transplantation

NCT ID: NCT01408797

Last Updated: 2011-08-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2013-03-31

Brief 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.

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.

Conditions

Renal Transplantation; Uremia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Donor specific transfusion

Subjects with uremia will undergo donor specific transfusion before transplantation

Group Type: EXPERIMENTAL

donor specific transfusion

Intervention Type: PROCEDURE

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

Clonal deletion

Group Type: EXPERIMENTAL

MMF, Bortezomib

Intervention Type: DRUG

MMF and Bortezomib will be administered after donor specific transfusion

Drugs Added When Needed

Group Type: EXPERIMENTAL

drugs added according to the immuno condition of the recipients

Intervention Type: PROCEDURE

drugs (corticosteroid, MMF and/or CNI) will be added according to the recipients immuno event and donor specific antibody

Interventions

donor specific transfusion

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

Intervention Type: PROCEDURE

MMF, Bortezomib

MMF and Bortezomib will be administered after donor specific transfusion

Intervention Type: DRUG

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

Intervention Type: PROCEDURE

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Terasaki Foundation

UNKNOWN

Sponsor Role: collaborator

Fuzhou General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Tan Jianming, MD,PhD

Principal Investigators

Tan Jianming, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Fuzhou General Hospital

Locations

No. 156, Xi er huan Road

Fuzhou, Fujian, China

Site Status: RECRUITING

Countries

China

Central Contacts

Tan Jianming, MD,PhD

Role: CONTACT

doctortjm@yahoo.com

8613375918000

Gao Xia, MD

Role: CONTACT

gaojxia@yahoo.com.cn

8615959165311

Facility Contacts

Tan Jianming, MD,PhD

Role: primary

doctortjm@yahoo.com

8613375918000

Gao Xia, MD

Role: backup

gaojxia@yahoo.com.cn

8615959165311

Other Identifiers

DAWN-2011-TJM

Identifier Type: -

Identifier Source: org_study_id