Renal Allograft Tolerance Through Mixed Chimerism - SMC/MGH

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.

Study Overview

• Status: Recruiting
• Conditions: Renal Failure
• Intervention / Treatment: Drug: Rituximab, Fludarabine, Cyclophosphamide, Thymic irradiation and Siplizumab; Procedure: Combined bone marrow and kidney transplant

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Tatsuo Kawai, MD PhD; Phone Number: 617-726-0289; Email: tkawai@mgh.harvard.edu
• Study Contact Backup: Name: Gabe Impreso Baysa, BS; Phone Number: 617-643-7569; Email: gimpresobaysa@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Tatsuo Kawai, MD, PhD; Phone Number: 617-726-0289; Email: tkawai@partners.org
      • Principal Investigator: Tatsuo Kawai, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.
• 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
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: August 18, 2020
• First Submitted That Met QC Criteria: September 1, 2020
• First Posted (Actual): September 7, 2020

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Cyclophosphamide; Rituximab; Fludarabine
• Other Study ID Numbers: Tolerance SMC-MGH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No