Clonal Deletion on Living-Relative Donor Kidney Transplantation

Renal Transplantation Clinical Trial

— DAWN  

Official title:

A Prospective, Open-Label, Pilot Study of Clonal Deletion on Living-Relative Donor Kidney Transplantation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01408797
• Other study ID #: DAWN-2011-TJM
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: August 2, 2011
• Last updated: August 19, 2011
• Start date: March 2011
• Est. completion date: March 2013

Study information

• Verified date: February 2011
• Source: Fuzhou General Hospital
• Contact: Tan Jianming, MD,PhD
• Phone: 8613375918000
• Email: doctortjm[@]yahoo.com
• Is FDA regulated: No
• Health authority: China:Fujian Province branch of Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Renal Transplantation
• Uremia

Intervention

Procedure:
• donor specific transfusion
before transplantation,200mL of donor whole blood will be transfused to the recipient

Drug:
• MMF, Bortezomib
MMF and Bortezomib will be administered after donor specific transfusion

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

Locations

Country	Name	City	State
China	No. 156, Xi er huan Road	Fuzhou	Fujian

Sponsors (2)

Lead Sponsor	Collaborator
Fuzhou General Hospital	Terasaki Foundation

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dosage of immunosuppressants	Effectiveness of clonal deletion on reducing the dosage of immunosuppressants (calcineurin inhibitor plus mycophenolate, azothioprine, or sirolimus).	one year	No
Secondary	immune event	Time to immune event (acute rejection or DSA);	1 year	Yes
Secondary	DSA	Proportion of patients who become positive for donor specific HLA antibodies post transplant	1 year	Yes
Secondary	DGF	Incidence of delayed graft function (defined as need for post-transplant dialysis)	1 years	Yes
Secondary	Renal function	Change in renal function as determined by estimated glomerular filtration rate and proteinuria (>1g) at 1 year post transplant	1 year	No
Secondary	Survival	Allograft Survival at 1 year post transplant	1 year	Yes