Renal Allograft Tolerance Through Mixed Chimerism (Belatacept)

NCT02314403 | Completed Phase 1 Results DMC

• 1 other identifier: MGH Tolerance Trial
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Kidney Failure, Chronic; Renal Insufficiency

Keywords

ESRD

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Successful Withdrawal of Immunosuppression

  The Primary Outcome is: The induction of transient mixed chimerism and renal allograft tolerance (24 consecutive months off of immunosuppression)

  5 Years

Study Arms (1)

Combined Bone Marrow and Kidney Transplantation

EXPERIMENTAL

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; Drug: ATG; Drug: Rituximab; Radiation: Total Body Irradiation; Radiation: Thymic Irradiation; Procedure: Combined Bone Marrow/Kidney Transplantation

Interventions

Belatacept DRUG

A selective T-cell (lymphocyte) costimulation blocker

Combined Bone Marrow and Kidney Transplantation

ATG DRUG

A T-Cell Depleting Agent

Combined Bone Marrow and Kidney Transplantation

Rituximab DRUG

B-Cell Depleting Agent

Combined Bone Marrow and Kidney Transplantation

Total Body Irradiation RADIATION

Combined Bone Marrow and Kidney Transplantation

Thymic Irradiation RADIATION

Combined Bone Marrow and Kidney Transplantation

Combined Bone Marrow/Kidney Transplantation PROCEDURE

Combined Bone Marrow and Kidney Transplantation

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Links

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

MeSH Terms

Conditions

Kidney Failure, Chronic; Renal Insufficiency

Interventions

Abatacept; Rituximab; Whole-Body Irradiation; Kidney Transplantation

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Immunoproteins; Radiotherapy; Therapeutics; Investigative Techniques; Renal Replacement Therapy; Organ Transplantation; Transplantation; Surgical Procedures, Operative; Urologic Surgical Procedures; Urogenital Surgical Procedures

Limitations and Caveats

The incidence of adverse events found around 10 days after bone marrow transplant.

Results Point of Contact

• Title: Tatsuo Kawai, MD PhD
• Organization: Massachusetts General Hospital

tkawai@mgh.harvard.edu

617-726-0289

Study Officials

• Tatsuo Kawai, MD PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Surgery, Harvard Medical School

Study Record Dates

• First Submitted: December 5, 2014
• First Posted: December 11, 2014
• Study Start: February 1, 2015
• Primary Completion: March 1, 2021
• Study Completion: July 1, 2021
• Last Updated: October 25, 2021
• Results First Posted: September 2, 2021

Record last verified: 2021-10

Locations

US (1)