End Stage Renal Disease
Conditions
Keywords
End Stage Renal Disease, Renal Transplant, Bone Marrow Transplant, Tolerance, Chimerism, 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
DRUGMEDI-507
T-Cell Depleting Agent
DRUGRituximab
B-Cell Depleting Agent
RADIATIONTotal Body Irradiation
Bone Marrow Depletion
RADIATIONThymic Irradiation
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 65 Years
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Successful Withdrawal of Immunosuppressive Therapy | 5 years | The primary endpoint is induction of transient mixed chimerism and renal allograft tolerance without engraftment syndrome or acute kidney injury |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Engraftment Syndrome | 5 Years | Constellation of symptoms known Engraftment Syndrome |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Combined Bone Marrow and Kidney Transplantation Conditioning regimen consisting of Rituximab, MEDI-507, Total Body Irradiation, Thymic Irradiation followed by simultaneous bone marrow and kidney transplantation
MEDI-507: T-Cell Depleting Agent
Rituximab: B-Cell Depleting Agent
Total Body Irradiation: Bone Marrow Depletion
Thymic Irradiation | 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 |
| 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
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
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined Bone Marrow and Kidney Transplantation | Successful Withdrawal of Immunosuppressive Therapy | 2 Participants |
Secondary
Number of Participants With Engraftment Syndrome
Constellation of symptoms known Engraftment Syndrome
Time frame: 5 Years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined Bone Marrow and Kidney Transplantation | Number of Participants With Engraftment Syndrome | 2 Participants |