Tolerance Through Mixed Chimerism (Sip-Tego)

Exclusion Criteria

• •1. ABO blood group-incompatible renal allograft
• •2. Participant with a donor-specific antibody (DSA) within 6 months prior to transplant
• •3. Persistent Leukopenia (WBC less than 2,000/mm3) or thrombocytopenia (\<100,000/mm3)
• •4. Seropositivity for HIV-1, hepatitis B core antigen, or hepatitis C virus (confirmed by hepatitis C virus RNA); or positivity for hepatitis B surface antigen.
• •5. Untreated Infection
• •6. Left ventricular ejection fraction \< 40% as determined by TTE or clinical evidence of heart failure.
• •7. Forced expiratory volume FEV1 or DLCO \< 50% of predicted.
• •8. Lactation or pregnancy.
• •9. Patients with active cancer or those with a high risk of recurrence following the American Transplant Society
• •10. Underlying renal disease etiology with a high risk of disease recurrence in the transplanted kidney (such as non-genetic primary focal segmental glomerulosclerosis dense deposit disease, C3 glomerulonephritis, and, atypical hemolytic uremic syndrome).
• •11. Prior dose-limiting radiation therapy for treatment of malignant disease.
• •12. 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. This includes long term cigarette smoking or a family history of malignancy.
• •13. Enrollment in other investigational drug studies within 30 days prior to enrollment.
• •14. Abnormal (\>2 times lab normal) values for (a) liver function chemistries (ALT, AST, AP), (b) bilirubin, (c) coagulation studies (PT, PTT) , or any patients on chronic anticoagulation therapy.
• •15. Allergy or sensitivity to any component of Cyclophosphamide, tacrolimus, Siplizumab, Tegoprubart, or rituximab.
• •16. The presence of any medical condition that the investigator deems incompatible with participation in the trial. This includes a history of alcohol abuse or illicit drug use/dependence.
• •17. Any chronic or intermittent administration of immunosuppressant medication (such as for inflammatory bowel disease or asthma)
• •18. Subjects who have non-insulin dependent diabetes (NIDDM) without good blood glucose control (HbA1c\<8%). Subjects with severe diabetes-related complications, such as advanced retinopathy, gastroparesis, or severe neuropathy that significantly impair their ability to perform normal, independent daily activities, will also be excluded.