Kidney Failure, Chronic, Renal Insufficiency
Conditions
Keywords
ESRD
Brief 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
Interventions
DRUGBelatacept
A selective T-cell (lymphocyte) costimulation blocker
DRUGATG
A T-Cell Depleting Agent
DRUGRituximab
B-Cell Depleting Agent
RADIATIONTotal Body Irradiation
RADIATIONThymic Irradiation
PROCEDURECombined Bone Marrow/Kidney Transplantation
Sponsors
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Successful Withdrawal of Immunosuppression | 5 Years | The Primary Outcome is: The induction of transient mixed chimerism and renal allograft tolerance (24 consecutive months off of immunosuppression) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Combined Bone Marrow and Kidney Transplantation 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.
Belatacept: A selective T-cell (lymphocyte) costimulation blocker
ATG: A T-Cell Depleting Agent
Rituximab: B-Cell Depleting Agent
Total Body Irradiation
Thymic Irradiation
Combined Bone Marrow/Kidney Transplantation | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | Combined Bone Marrow and Kidney Transplantation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Age, Continuous | 37 years STANDARD_DEVIATION 5.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 2 |
| other Total, other adverse events | 2 / 2 |
| serious Total, serious adverse events | 1 / 2 |
Outcome results
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)
Time frame: 5 Years
Population: Two subjects underwent conditioning regimen
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined Bone Marrow and Kidney Transplantation | Number of Participants With Successful Withdrawal of Immunosuppression | 2 Participants |