Renal Allograft Tolerance Through Mixed Chimerism (Belatacept)

Mass General Brigham

Status and phase

Completed

Phase 1

Conditions

Renal Insufficiency

Kidney Failure, Chronic

Treatments

Procedure: Combined Bone Marrow/Kidney Transplantation

Drug: Rituximab

Radiation: Thymic Irradiation

Drug: Belatacept

Radiation: Total Body Irradiation

Drug: ATG

Study type

Interventional

Funder types

Other

Identifiers

NCT02314403

MGH Tolerance Trial

Details and patient eligibility

About

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

Enrollment

2 patients

Sex

All

Ages

18 to 60 years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

2 participants in 1 patient group

Combined Bone Marrow and Kidney Transplantation

Experimental group

Description:

Recipients will receive a conditioning regimen that starts with Rituximab on day -7 (and days -2, 5, 12), Whole Body Irradiation 1.5 Gy x2 on study days -6 and -5, followed by ATG on Days -2, -1, 0. Belatacept 10mg/kg on Days 0, 3, 10, 17, 24, 38, 52. Thymic irradiation (7 Gy) will be given on study day -1, and combined renal and bone marrow transplant will be done on study day 0. Prednisone will be started at 2 mg/kg on day 4 and tapered off by day 20. Tacrolimus will be administered on study days -1 through 60, and then tapered if weaning criteria are met.