NCT05900401

Delayed Tolerance Through Mixed Chimerism

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Massachusetts General Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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

Detailed 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). Prophylaxis will be provided for hemorrhagic cystitis, PCP, fungal infection, CMV, and perioperative infection. All patients who require any blood transfusion will receive only leukocyte-depleted and irradiated blood products for a period of at least 12 months following HSC Transplant. The recipients will undergo renal allograft biopsy at 6 months after HSCT. If the I.S. withdrawal criteria are met, I.S. will be slowly tapered off by 9-12 months

Conditions

• Kidney Failure
• Kidney Transplant; Complications
• Chimera

Interventions

Type	Name	Description
OTHER	Bone 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)
PROCEDURE	Peripheral 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.
DRUG	Fludarabine	Fludarabine 15 mg/m2/day on days -5 to -3 (3 doses)
DRUG	Cyclophosphamide	Cyclophosphamide (CP) 30 mg/kg/day on days -5 and -4
DRUG	Rituximab	Rituximab on study day -6
DRUG	Siplizumab	Siplizumab (anti-CD2 mAb) on days, -2, -1, 0 and +1.

Timeline

• Start date: 2023-10-01
• Primary completion: 2028-12-01
• Completion: 2030-12-01
• First posted: 2023-06-12
• Last updated: 2025-12-09

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study