Clinical trial NCT04540380: Renal Allograft Tolerance Through Mixed Chimerism - SMC/MGH
Official title: Renal Allograft Tolerance Through Mixed Chimerism - SMC/MGH
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Renal Failure
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2020-09-07
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Transient Chimerism
timeFrame: 36 months after immunosuppression withdrawal
measure: Incidence of Chimerism Transition Syndrome
timeFrame: 36 months after immunosuppression withdrawal
measure: Incidence of tolerance induction
timeFrame: 36 months after immunosuppression withdrawal
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
References: