Renal Allograft Tolerance Through Mixed Chimerism (Belatacept)

Kidney Failure, Chronic Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02314403
• Other study ID #: MGH Tolerance Trial
• Status: Completed
• Phase: Phase 1
• Start date: February 2015
• Est. completion date: July 2021

Study information

• Verified date: October 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: July 2021
• Est. primary completion date: March 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Male or female 18-60 years of age

• Candidate for a living-donor renal allograft from an HLA mismatched donor

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

• Use of FDA-approved methods of contraception by all recipients from the time that study treatment begins until 104 weeks (24 months) after renal transplantation.

• Ability to understand and provide informed consent.

• Serologic evidence of prior exposure to EBV.

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)

• Leukopenia or thrombocytopenia.

• Positive for HIV-1, hepatitis B core antigen, or hepatitis C virus; or positivity for hepatitis B surface antigen.

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

• Forced expiratory volume FEV1 < 50% of predicted.

• Lactation or pregnancy.

• 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 membranoprolifertive glomerulonephritis).

• Prior dose-limiting radiation therapy.

• Known genetic disease or family history that may result in greater sensitivity to the effects of irradiation, or a physical deformity that would preclude adequate shielding or appropriate dosing during the irradiation component of the conditioning regimen.

• Enrollment in other investigational drug studies within 30 days prior to enrollment.

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

• Allergy or sensitivity to any component of belatacept, ATG, tacrolimus, or rituximab.

• Maintenance immunosuppression within 3 months prior to conditioning other than physiological doses of steroids, defined as = 50 mg of hydrocortisone or dose equivalent.

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

Related Conditions & MeSH terms

• Kidney Failure, Chronic
• Renal Insufficiency

Intervention

Drug:
• Belatacept
A selective T-cell (lymphocyte) costimulation blocker
• ATG
A T-Cell Depleting Agent
• Rituximab
B-Cell Depleting Agent

Radiation:
• Total Body Irradiation

• Thymic Irradiation

Procedure:
• Combined Bone Marrow/Kidney Transplantation

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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Successful Withdrawal of Immunosuppression	The Primary Outcome is: The induction of transient mixed chimerism and renal allograft tolerance (24 consecutive months off of immunosuppression)	5 Years

External Links

•   Kawai T, (et.al.) HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2008 Jan 24;358(4):353-61.
•   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.
•   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.