Renal Allograft Tolerance Through Mixed Chimerism (Belatacept)

October 4, 2021 updated by: Tatsuo Kawai, MD, PhD, Massachusetts General Hospital
This study will examine the safety and effectiveness of a combination kidney and bone marrow transplant from a haplo-identical related donor. An investigational medication and other treatments will be given prior to and after the transplant to help protect the transplanted kidney from being attacked by the body's immune system

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

2

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

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.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female 18-60 years of age
  • Candidate for a living-donor renal allograft from an HLA mismatched donor
  • First or second transplant with either a living donor or cadaveric transplant as the first transplant.
  • Use of FDA-approved methods of contraception by all recipients from the time that study treatment begins until 104 weeks (24 months) after renal transplantation.
  • Ability to understand and provide informed consent.
  • Serologic evidence of prior exposure to EBV.

Exclusion Criteria:

  • ABO blood group-incompatible renal allograft.
  • Evidence of anti-HLA antibody within 60 days prior to transplant as assessed by routine methodology (AHG and/or ELISA)
  • Leukopenia or thrombocytopenia.
  • Positive for HIV-1, hepatitis B core antigen, or hepatitis C virus; or positivity for hepatitis B surface antigen.
  • Cardiac ejection fraction < 40% or clinical evidence of insufficiency.
  • Forced expiratory volume FEV1 < 50% of predicted.
  • Lactation or pregnancy.
  • History of cancer other than basal cell carcinoma of the skin or carcinoma in situ of the cervix.
  • Underlying renal disease etiology with a high risk of disease recurrence in the transplanted kidney (such as focal segmental glomerulosclerosis, type I or II membranoprolifertive glomerulonephritis).
  • 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 belatacept, ATG, tacrolimus, or rituximab.
  • Maintenance immunosuppression within 3 months prior to conditioning other than physiological doses of steroids, defined as ≤ 50 mg of hydrocortisone or dose equivalent.
  • The presence of any medical condition that the investigator deems incompatible with participation in the trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Combined Bone Marrow and Kidney Transplantation
Recipients will receive a conditioning regimen that starts with Rituximab on day -7 (and days -2, 5, 12), Whole Body Irradiation 1.5 Gy x2 on study days -6 and -5, followed by ATG on Days -2, -1, 0. Belatacept 10mg/kg on Days 0, 3, 10, 17, 24, 38, 52. Thymic irradiation (7 Gy) will be given on study day -1, and combined renal and bone marrow transplant will be done on study day 0. Prednisone will be started at 2 mg/kg on day 4 and tapered off by day 20. Tacrolimus will be administered on study days -1 through 60, and then tapered if weaning criteria are met.
Drug: Belatacept
A selective T-cell (lymphocyte) costimulation blocker
Drug: ATG
A T-Cell Depleting Agent
Drug: Rituximab
B-Cell Depleting Agent
Radiation: Total Body Irradiation
Radiation: Thymic Irradiation
Procedure: Combined Bone Marrow/Kidney Transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Successful Withdrawal of Immunosuppression
Time Frame: 5 Years
The Primary Outcome is: The induction of transient mixed chimerism and renal allograft tolerance (24 consecutive months off of immunosuppression)
5 Years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Investigators

  • Principal Investigator: Tatsuo Kawai, MD PhD, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

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 Major Dates

Study Start

February 1, 2015

Primary Completion (Actual)

March 1, 2021

Study Completion (Actual)

July 1, 2021

Study Registration Dates

First Submitted

December 5, 2014

First Submitted That Met QC Criteria

December 8, 2014

First Posted (Estimate)

December 11, 2014

Study Record Updates

Last Update Posted (Actual)

October 25, 2021

Last Update Submitted That Met QC Criteria

October 4, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MGH Tolerance Trial

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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