Renal Allograft Tolerance Through Mixed Chimerism (Belatacept)

NCT ID: NCT02314403

Last Updated: 2021-10-25

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

2 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-02-28

Study Completion Date

2021-07-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Kidney Failure, Chronic Renal Insufficiency

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Group Type EXPERIMENTAL

Belatacept

Intervention Type DRUG

A selective T-cell (lymphocyte) costimulation blocker

ATG

Intervention Type DRUG

A T-Cell Depleting Agent

Rituximab

Intervention Type DRUG

B-Cell Depleting Agent

Total Body Irradiation

Intervention Type RADIATION

Thymic Irradiation

Intervention Type RADIATION

Combined Bone Marrow/Kidney Transplantation

Intervention Type PROCEDURE

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Belatacept

A selective T-cell (lymphocyte) costimulation blocker

Intervention Type DRUG

ATG

A T-Cell Depleting Agent

Intervention Type DRUG

Rituximab

B-Cell Depleting Agent

Intervention Type DRUG

Total Body Irradiation

Intervention Type RADIATION

Thymic Irradiation

Intervention Type RADIATION

Combined Bone Marrow/Kidney Transplantation

Intervention Type PROCEDURE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Massachusetts General Hospital

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Tatsuo Kawai, MD, PhD

Associate Professor of Surgery, Harvard Medical School

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Tatsuo Kawai, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Related Links

Access external resources that provide additional context or updates about the study.

http://www.ncbi.nlm.nih.gov/pubmed/21666482?dopt=Abstract

Kawai T, Cosimi AB, Sachs DH. Preclinical and clinical studies on the induction of renal allograft tolerance through transient mixed chimerism. Curr Opin Organ Transplant. 2011 Aug;16(4):366-71.

http://www.ncbi.nlm.nih.gov/pubmed/21839648?dopt=Abstract

Sachs DH, Sykes M, Kawai T, Cosimi AB. Immuno-intervention for the induction of transplantation tolerance through mixed chimerism. Semin Immunol. 2011 Jun;23(3):165-73.

http://www.ncbi.nlm.nih.gov/pubmed/18216355?dopt=Abstract

Kawai T, (et.al.) HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2008 Jan 24;358(4):353-61.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

MGH Tolerance Trial

Identifier Type: -

Identifier Source: org_study_id