Tolerance Through Mixed Chimerism (Sip-Tego)
Tatsuo Kawai, MD, PhD
Summary
This is an open-label, single-institution study to assess the safety and the efficacy of the Sip-Tego regimen for the induction of donor-specific immunologic unresponsiveness to a renal allograft. The investigators propose to treat 6 adult subjects in end-stage renal disease (ESRD) who do not demonstrate evidence of prior sensitization.
Description
The conditioning regimen to be used in this protocol consists of an ordered series of procedures and treatments including thymic irradiation, low-dose cyclophosphamide, antibody administration (Siplizumab, rituximab and tegoprubart), and bone marrow cell infusion. The surgical techniques for the renal transplant will be accomplished according to the surgeon's clinical judgment and experience using standard techniques in use at the institution. The donor nephrectomy will be accomplished according to the surgeon's clinical judgment and experience. The conditioning regimen requires six days leadi…
Eligibility
- Age range
- 18–65 years
- Sex
- All
- Healthy volunteers
- No
Recipient Inclusion Criteria: 1. Male or female 18-65 years of age. 2. Subjects with chronic kidney disease stage V (GFR\<15ml/min/1.73m2) or ESRD who are treated or imminently be treated with either hemodialysis or peritoneal dialysis. 3. Candidate for a living-donor renal allograft from an HLA matched or mismatched donor 4. First or second renal transplant. 5. EBV Seropositive 6. 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 7. Ability to understand and provide informed consent…
Interventions
- ProcedureCombined Kidney/Bone Marrow Transplant
The conditioning regimen to be used in this protocol consists of an ordered series of procedures and treatments including thymic irradiation, low-dose cyclophosphamide, antibody administration (Siplizumab, rituximab and tegoprubart), and bone marrow cell infusion.
- ProcedureDonation of Kidney / Bone Marrow
The donor will undergo nephrectomy and under general anesthesia. Donors will undergo bone marrow harvested under general anesthesia. Sufficient marrow will be obtained to provide at least 2 x 108 nucleated cells per kilogram weight of the recipient.
- DrugConditioning Regimen (Rituxan, Siplizumab, Cyclophosphamide, Tegoprubart)
Recipients will receive a conditioning regimen that includes rituximab on study day -6 and -2, Siplizumab (0.6mg/kg) on day -6, -1, 0 and +1, cyclophosphamide (CP, 22.5mg/kg) on days -5 and -4. Tegoprubart (Fc-modified anti-CD154 mAB, Eledon Pharm) 20mg/kg will be administered on days 0, 2, 5, 12 and 19).
Location
- Massachusetts General HospitalBoston, Massachusetts