Renal Allograft Tolerance Through Mixed Chimerism

Study Overview
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Brief Summary
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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

Official Title
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Renal Allograft Tolerance Through Mixed Chimerism

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Drug: MEDI-507
* Drug: Rituximab
* Radiation: Total Body Irradiation
* Radiation: Thymic Irradiation


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combined Bone Marrow and Kidney Transplantation<br>Conditioning regimen consisting of Rituximab, MEDI-507, Total Body Irradiation, Thymic Irradiation followed by simultaneous bone marrow and kidney transplantation | Drug: MEDI-507<br>* T-Cell Depleting Agent<br>Drug: Rituximab<br>* B-Cell Depleting Agent<br>Radiation: Total Body Irradiation<br>* Bone Marrow Depletion<br>Radiation: Thymic Irradiation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Engraftment Syndrome | Constellation of symptoms known Engraftment Syndrome | 5 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chimerism, End Stage Renal Disease, Renal Transplant, Bone Marrow Transplant, Tolerance, ESRD