Renal Allograft Tolerance Through Mixed Chimerism

End Stage Renal Disease Clinical Trial

Official title:

Renal Allograft Tolerance Through Mixed Chimerism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01780454
• Other study ID #: 2013P000822
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 2013
• Est. completion date: June 2020

Study information

• Verified date: March 2021
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will examine the safety and effectiveness of a combination kidney and bone marrow transplant from a haplo-identical related donor. An investigational medication and other treatments will be given prior to and after the transplant to help protect the transplanted kidney from being attacked by the body's immune system

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2
• Est. completion date: June 2020
• Est. primary completion date: June 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Key Inclusion Criteria:

• Male or female 18-60 years of age

• Candidate for a living-donor renal allograft with a one haplotype identical donor identified.

• First or second transplant with either a living donor or cadaveric transplant as the first transplant.

• Positive serologic testing for EBV indicating past exposure.

Key Exclusion Criteria:

• ABO blood group-incompatible renal allograft.

• Evidence of anti-HLA antibody within 60 days prior to transplant as assessed by routine methodology (AHG and/or ELISA)

• Positive testing for: HIV, hepatitis B core antigen, or hepatitis C virus or positivity for hepatitis B surface antigen.

• Cardiac ejection fraction < 40% or clinical evidence of insufficiency.

• History of cancer other than basal cell carcinoma of the skin or carcinoma in situ of the cervix.

• Underlying renal disease etiology with a high risk of disease recurrence in the transplanted kidney (such as focal segmental glomerulosclerosis, type I or II nonproliferative glomerulonephritis).

• Prior dose-limiting radiation therapy.

• Abnormal (>2 times lab normal) values for (a) liver function chemistries (ALT, AST, AP), (b) bilirubin, (c) coagulation studies (PT, PTT).

• The presence of any medical condition that the investigator deems incompatible with participation in the trial.

Related Conditions & MeSH terms

• End Stage Renal Disease
• Kidney Diseases
• Kidney Failure, Chronic

Intervention

Drug:
• MEDI-507
T-Cell Depleting Agent
• Rituximab
B-Cell Depleting Agent

Radiation:
• Total Body Irradiation
Bone Marrow Depletion
• Thymic Irradiation

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

References & Publications (3)

Kawai T, Cosimi AB, Sachs DH. Preclinical and clinical studies on the induction of renal allograft tolerance through transient mixed chimerism. Curr Opin Organ Transplant. 2011 Aug;16(4):366-71. doi: 10.1097/MOT.0b013e3283484b2c. Review. — View Citation

Kawai T, Cosimi AB, Spitzer TR, Tolkoff-Rubin N, Suthanthiran M, Saidman SL, Shaffer J, Preffer FI, Ding R, Sharma V, Fishman JA, Dey B, Ko DS, Hertl M, Goes NB, Wong W, Williams WW Jr, Colvin RB, Sykes M, Sachs DH. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2008 Jan 24;358(4):353-61. doi: 10.1056/NEJMoa071074. — View Citation

Sachs DH, Sykes M, Kawai T, Cosimi AB. Immuno-intervention for the induction of transplantation tolerance through mixed chimerism. Semin Immunol. 2011 Jun;23(3):165-73. doi: 10.1016/j.smim.2011.07.001. Epub 2011 Aug 11. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Successful Withdrawal of Immunosuppressive Therapy	The primary endpoint is induction of transient mixed chimerism and renal allograft tolerance without "engraftment syndrome" or "acute kidney injury"	5 years
Secondary	Number of Participants With Engraftment Syndrome	Constellation of symptoms known "Engraftment Syndrome"	5 Years