ACTIVE_NOT_RECRUITING

Renal Allograft Tolerance Through Mixed Chimerism - SMC/MGH

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Renal Allograft Tolerance Through Mixed Chimerism - SMC/MGH

Quick Facts

Study Start:2021-09-01

Study Completion:2027-06

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT04540380

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 65 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	* 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

Inclusion Criteria

Exclusion 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

* 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

Contacts and Locations

Study Locations (Sites)

Massachusetts General Hospital

Boston, Massachusetts, 02114

United States

Collaborators and Investigators

Sponsor: Massachusetts General Hospital

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-09-01

Study Completion Date2027-06

Study Record Updates

Study Start Date2021-09-01

Study Completion Date2027-06

Terms related to this study

Additional Relevant MeSH Terms

Renal Failure