Delayed Tolerance Through Mixed Chimerism

Phase 1

Recruiting

• Conditions: Kidney Failure; Kidney Transplant; Complications; Chimera
• Interventions: Other: Bone Marrow Transplant; Procedure: Peripheral Blood Stem Cell Collection; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Rituximab; Drug: Siplizumab

• Registration Number: NCT05900401
• Lead Sponsor: Massachusetts General Hospital

Brief 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

Study Timeline

• Study First Submitted: 2023-05-18
• Study First Submitted QC: 2023-06-09
• Study First Posted: 2023-06-12
• Study Start: 2023-10-01
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-04
• Last Update Posted: 2024-06-06
• Primary Completion: 2028-12
• Study Completion: 2030-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Kidney and Stem Cell Recipients	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)
Kidney and Stem Cell Recipients	Fludarabine	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)
Kidney and Stem Cell Recipients	Rituximab	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)
Kidney and Stem Cell Donors	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
Kidney and Stem Cell Recipients	Cyclophosphamide	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)
Kidney and Stem Cell Recipients	Siplizumab	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)

Primary Outcome Measures

Name	Time	Method
Incidence of transient mixed chimerism	3 months
Incidence of renal allograft tolerance	2 years after immunosuppression withdrawal

Secondary Outcome Measures

Name	Time	Method
Incidence of Allograft Rejection	2 years after immunosuppression withdrawal	Measuring incidence of acute or chronic rejection free survival
Incidence of DSA	2 years after immunosuppression withdrawal
Incidence of thymic irradiation toxicities	2 years after immunosuppression withdrawal
Incidence of Graft Survival	2 years after immunosuppression withdrawal
Incidence of Chimeric Transition Syndrome	3 months
Incidence of infections	2 years after immunosuppression withdrawal	Clinically significant, invasive or resistant opportunistic infection
Incidence of Participant Survival	2 years after immunosuppression withdrawal
Incidence of GvHD	2 years after immunosuppression withdrawal

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States