Renal Allograft Tolerance Through Mixed Chimerism - SMC/MGH

Mass General Brigham

Status and phase

Active, not recruiting

Phase 1

Conditions

Renal Failure

Treatments

Procedure: Combined bone marrow and kidney transplant

Drug: Rituximab, Fludarabine, Cyclophosphamide, Thymic irradiation and Siplizumab

Study type

Interventional

Funder types

Other

Identifiers

NCT04540380

Tolerance SMC-MGH

Details and patient eligibility

About

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.

Enrollment

20 estimated patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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