Renal Allograft Tolerance Through Mixed Chimerism - SMC/MGH
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Outcome Measures
Primary Outcome Measures
- Incidence of Transient Chimerism [36 months after immunosuppression withdrawal]
- Incidence of Chimerism Transition Syndrome [36 months after immunosuppression withdrawal]
- Incidence of tolerance induction [36 months after immunosuppression withdrawal]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male or female 18-60 years of age.
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Candidate for a living-donor renal allograft from an HLA mismatched donor
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Subjects with chronic kidney disease stage or ESRD who are treated with either hemodialysis or peritoneal dialysis.
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First transplant.
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Use of FDA-approved methods of contraception
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Ability to understand and provide informed consent.
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Serologic evidence of prior exposure to EBV
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Negative COVID at screening and 2 days before procedure
Exclusion Criteria:
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ABO blood group-incompatible renal allograft.
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Evidence of anti-HLA antibody (donor specific or not) within 60 days prior to transplant as assessed by routine methodology (Luminex)
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Persistent Leukopenia (WBC less than 2,000/mm3) or thrombocytopenia (<100,000/mm3).
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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.
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Active infection
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Left ventricular ejection fraction < 40% as determined by TTE or clinical evidence of heart failure
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Forced expiratory volume FEV1 or DLCO < 50% of predicted.
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Lactation or pregnancy
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History of cancer other than basal cell carcinoma of the skin or carcinoma in situ of the cervix
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Underlying renal disease etiology with a high risk of disease recurrence in the transplanted kidney (such as focal segmental glomerulosclerosis).
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Prior dose-limiting radiation therapy
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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
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Enrollment in other investigational drug studies within 30 days prior to enrollment
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Abnormal (>2 times lab normal) values for (a) liver function chemistries (ALT, AST, AP), (b) bilirubin, (c) coagulation studies (PT, PTT).
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Allergy or sensitivity to any component of Siplizumab, Fludarabine, Cyclophosphamide tacrolimus, MMF or rituximab
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The presence of any medical condition that the investigator deems incompatible with participation in the trial.
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
Sponsors and Collaborators
- Massachusetts General Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Tolerance SMC-MGH