Bortezomib With Steroid Pulse Therapy for Acute Cellular Rejection in Kidney Transplantation

Kidney Transplantation Clinical Trial

Official title:

Bortezomib With Steroid Pulse Therapy for Acute Cellular Rejection in Kidney

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02351427
• Other study ID #: 2014-1223
• Status: Recruiting
• Phase: Phase 3
• First received: January 27, 2015
• Last updated: February 3, 2015
• Start date: February 2015
• Est. completion date: December 2015

Study information

• Verified date: February 2015
• Source: Asan Medical Center
• Contact: Su-Kil Park, M.D., PhD
• Phone: 82-2-3010-3263
• Email: skpark[@]amc.seoul.kr
• Is FDA regulated: No
• Health authority: Korea: Ministry of Food and Drug Safety
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether bortezomib is effective in the treatment of acute cellular rejection after kidney transplantation.

Description:

When acute cellular rejection occurred in kidney allograft, investigators administer high dose steroid. However, there is insufficient effect in about 20-30%. Bortezomib acts not only on plasma cells, but also T cells, B cells and dendritic cells. In addition, bortezomib is relatively safe drug compared to thymoglobulin which investigators use in the cases of steroid failure. Therefore, investigators administer bortezomib with steroid in one group, and compared the group with the other group in which conventional steroid treatment is done.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

• living donor kidney transplantation recipients

• patients who were performed kidney biopsies because of laboratory and clinically suspected rejection

• Biopsy proven acute cellular rejection (Banff I - IIA) with C4d negative

• Single luminex panel reactive antibody (PRA) I & II mean fluorescent intensity (MFI) < 3000

Exclusion Criteria:

• patients who received other major organ transplantation

• combined with urinary tract infection or obstruction

• combined with acute antibody mediated rejection

• poor compliance

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Transplantation

Intervention

Drug:
• Bortezomib
In one group, investigators administer bortezomib and steroid to manage acute cellular rejection in kidney transplantation, and compare the results with another group in which only steroid was administered.
• Steroid
Investigators administer steroid in both groups for conventional treatment of acute cellular rejection.

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Asan Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (9)

Arnulf B, Pylypenko H, Grosicki S, Karamanesht I, Leleu X, van de Velde H, Feng H, Cakana A, Deraedt W, Moreau P. Updated survival analysis of a randomized phase III study of subcutaneous versus intravenous bortezomib in patients with relapsed multiple myeloma. Haematologica. 2012 Dec;97(12):1925-8. doi: 10.3324/haematol.2012.067793. Epub 2012 Jun 11. — View Citation

Everly MJ, Everly JJ, Susskind B, Brailey P, Arend LJ, Alloway RR, Roy-Chaudhury P, Govil A, Mogilishetty G, Rike AH, Cardi M, Wadih G, Tevar A, Woodle ES. Bortezomib provides effective therapy for antibody- and cell-mediated acute rejection. Transplantat — View Citation

Hu X, Xu J, Sun A, Shen Y, He G, Guo F. Successful T-cell acute lymphoblastic leukemia treatment with proteasome inhibitor bortezomib based on evaluation of nuclear factor-?B activity. Leuk Lymphoma. 2011 Dec;52(12):2393-5. doi: 10.3109/10428194.2011.593271. Epub 2011 Jul 12. — View Citation

Kim SJ, Yoon DH, Kang HJ, Kim JS, Park SK, Kim HJ, Lee J, Ryoo BY, Ko YH, Huh J, Yang WI, Kim HK, Min SK, Lee SS, Do IG, Suh C, Kim WS; Consortium for Improving Survival of Lymphoma (CISL) investigators. Bortezomib in combination with CHOP as first-line treatment for patients with stage III/IV peripheral T-cell lymphomas: a multicentre, single-arm, phase 2 trial. Eur J Cancer. 2012 Nov;48(17):3223-31. doi: 10.1016/j.ejca.2012.06.003. Epub 2012 Jul 4. — View Citation

Lemy A, Toungouz M, Abramowicz D. Bortezomib: a new player in pre- and post-transplant desensitization? Nephrol Dial Transplant. 2010 Nov;25(11):3480-9. doi: 10.1093/ndt/gfq502. Epub 2010 Sep 8. Review. — View Citation

Schmidt N, Alloway RR, Walsh RC, Sadaka B, Shields AR, Girnita AL, Hanseman DJ, Woodle ES. Prospective evaluation of the toxicity profile of proteasome inhibitor-based therapy in renal transplant candidates and recipients. Transplantation. 2012 Aug 27;94(4):352-61. — View Citation

Tzvetanov I, Spaggiari M, Joseph J, Jeon H, Thielke J, Oberholzer J, Benedetti E. The use of bortezomib as a rescue treatment for acute antibody-mediated rejection: report of three cases and review of literature. Transplant Proc. 2012 Dec;44(10):2971-5. doi: 10.1016/j.transproceed.2012.02.037. Review. — View Citation

Walsh RC, Alloway RR, Girnita AL, Woodle ES. Proteasome inhibitor-based therapy for antibody-mediated rejection. Kidney Int. 2012 Jun;81(11):1067-74. doi: 10.1038/ki.2011.502. Epub 2012 Feb 15. Review. — View Citation

Zain JM, O'Connor O. Targeted treatment and new agents in peripheral T-cell lymphoma. Int J Hematol. 2010 Jul;92(1):33-44. doi: 10.1007/s12185-010-0614-9. Epub 2010 Jun 10. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum creatinine	Investigators measure patients' serum creatinine at day 14.	Day 14	No
Secondary	Incidence of steroid failure	Steroid failure is defined as serum creatinine at day 8 = serum creatinine at day 0.	Day 7	No
Secondary	Serum creatinine	Investigators measure patients' serum creatinine at month 1.	Month 1	No
Secondary	Infection	Infection as measured by clinical, laboratory and microbiological data	Until 1 year after intervention	Yes
Secondary	Recurrence of Rejection	Recurrence of rejection as measured by clinical and laboratory data with graft biopsy.	Until 1 year after intervention	No