Delayed Tolerance Through Mixed Chimerism
Massachusetts General Hospital
Summary
This study will examine the safety and effectiveness of a bone marrow transplant after kidney transplant (from either a living or deceased 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
Description
Recipients of previous living donor (LD) or deceased donor (DD) kidney transplants that were maintained on conventional immunosuppression (I.S.), will receive a conditioning regimen that includes rituximab on study day -6, fludarabine 15 mg/m2/day on days -5 to -3 (3 doses), Cyclophosphamide (30 mg/kg/day) on days -5 and -4, followed by local thymic irradiation (7 Gy) on day -1 and Siplizumab (anti-CD2 mAb) on days, -2, -1, 0 and +1. Donor hematopoetic stem cells (HSCs) will be infused on study day 0. Methylprednisolone 250mg/day will be started on day 0 and tapered off by day 20 (Fig. 2). Pro…
Eligibility
- Age range
- 18–65 years
- Sex
- All
- Healthy volunteers
- No
Recipient Inclusion Criteria 1. Male or female 18-65 years of age. 2. Kidney transplant recipients from either LD or DD, with cryo-preserved HSCs available, good renal function (GFR\>60 ml/min/1.73m2), normal current allograft biopsy, and no history of documented rejection episodes. 3. First or second renal transplant. 4. Use of FDA-approved methods of contraception (those with less than a 3% failure rate) by all recipients from the time that study treatment begins until 104 weeks (24 months) after renal transplantation. (For further information on FDA- approved methods of contraception, see…
Interventions
- OtherBone Marrow Transplant
Months-Years after standard transplant, patients will undergo bone marrow transplant (either from prospective collection of stem cells from their living donor, or from bone marrow collected at the time of deceased donation)
- ProcedurePeripheral Blood Stem Cell Collection
PBSC will be collected from the LD via leukapheresis 1-4 weeks before the scheduled HSCT. The donor will first undergo standard GCSF mobilization: GCSF (can be TBO-GCSF) dosed at 10 mcg/kg/d (rounded to nearest pre-filled syringe) administered subcutaneously daily for 5 consecutive days. On the 5th day, the donor will undergo standard large volume leukapheresis. The target yield will be 2-3 x 106 CD34+ cells / kg of actual recipient body weight. A maximum of 3 days of pheresis will be allowed. A minimum of 2 x 106 CD34+ cells / kg of actual recipient body weight will be required to proceed.
- DrugFludarabine
Fludarabine 15 mg/m2/day on days -5 to -3 (3 doses)
- DrugCyclophosphamide
Cyclophosphamide (CP) 30 mg/kg/day on days -5 and -4
- DrugRituximab
Rituximab on study day -6
- DrugSiplizumab
Siplizumab (anti-CD2 mAb) on days, -2, -1, 0 and +1.
Location
- Massachusetts General HospitalBoston, Massachusetts