Renal Allograft Tolerance Through Mixed Chimerism - SMC/MGH

• Status: Not yet recruiting
• Trial end date: 2025-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Massachusetts General Hospital
• Treatments: Cyclophosphamide; Fludarabine; Rituximab; Thymoglobulin

Criteria

Inclusion Criteria:

• Male or female 18-60 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.

• Serologic evidence of prior exposure to EBV

• Negative COVID at screening and 2 days before procedure

Exclusion Criteria:

• ABO blood group-incompatible renal allograft.

• Evidence of anti-HLA antibody (donor specific or not) within 60 days prior to transplant as assessed by routine methodology (Luminex)

• 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 other than basal cell carcinoma of the skin or carcinoma in situ of the cervix

• 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, 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