Renal Allograft Tolerance Through Mixed Chimerism - SMC/MGH

Phase 1

Recruiting

• Conditions: Renal Failure

• Registration Number: NCT04540380
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

The goal is to investigate the safety of the conditioning regimen, and its ability to induce donor/recipient lymphohematopoietic chimerism without Chimerism Transition Syndrome (CTS), which may result in donor-specific unresponsiveness (tolerance) to the renal allograft in the absence of maintenance immunosuppression.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-08-18
• Study First Submitted QC: 2020-09-01
• Study First Posted: 2020-09-07
• Study Start: 2021-09-01
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-04
• Last Update Posted: 2024-06-06
• Primary Completion: 2025-01
• Study Completion: 2025-06

Recruitment & Eligibility

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

Inclusion Criteria

• Male or female 18-65 years of age.
• Candidate for a living-donor renal allograft from an HLA mismatched donor
• Subjects with chronic kidney disease stage or ESRD who are treated with either hemodialysis or peritoneal dialysis.
• First transplant.
• Use of FDA-approved methods of contraception
• Ability to understand and provide informed consent.
• Negative COVID at screening and 2 days before procedure

Exclusion Criteria

• ABO blood group-incompatible renal allograft.
• Participant with a (non DSA) PRA > 20% within 6 months prior to transplant
• Persistent Leukopenia (WBC less than 2,000/mm3) or thrombocytopenia (<100,000/mm3).
• 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.
• Active infection
• Left ventricular ejection fraction < 40% as determined by TTE or clinical evidence of heart failure
• Forced expiratory volume FEV1 or DLCO < 50% of predicted.
• Lactation or pregnancy
• History of cancer (following the American Transplant Society Guidelines)
• Underlying renal disease etiology with a high risk of disease recurrence in the transplanted kidney (such as focal segmental glomerulosclerosis).
• Prior dose-limiting radiation therapy
• 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
• Enrollment in other investigational drug studies within 30 days prior to enrollment
• Abnormal (>2 times lab normal) values for (a) liver function chemistries (ALT, AST, AP), (b) bilirubin, (c) coagulation studies (PT, PTT).
• Allergy or sensitivity to any component of Siplizumab, Fludarabine, Cyclophosphamide, tacrolimus, DMSO, MMF or rituximab.
• The presence of any medical condition that the investigator deems incompatible with participation in the trial.
• Subjects who have non-insulin dependent diabetes (NIDDM) without good blood glucose control (HbA1c<7). Subject with severe retinopathy, gastroparesis, or severe neuropathy which prevent subject's normal independent daily activities will be excluded from the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Incidence of Chimerism Transition Syndrome	36 months after immunosuppression withdrawal
Incidence of tolerance induction	36 months after immunosuppression withdrawal
Incidence of Transient Chimerism	36 months after immunosuppression withdrawal

Trial Locations

Locations (1)

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