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Renal Allograft Tolerance Through Mixed Chimerism (Belatacept)

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ClinicalTrials.gov Identifier: NCT02314403
Recruitment Status : Active, not recruiting
First Posted : December 11, 2014
Last Update Posted : April 12, 2019
Sponsor:
Information provided by (Responsible Party):
Tatsuo Kawai, MD, PhD, Massachusetts General Hospital

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

Condition or disease Intervention/treatment Phase
Kidney Failure, Chronic Renal Insufficiency Drug: Belatacept Drug: ATG Drug: Rituximab Radiation: Total Body Irradiation Radiation: Thymic Irradiation Procedure: Combined Bone Marrow/Kidney Transplantation Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 5 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Study Start Date : February 2015
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : August 2021

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



Primary Outcome Measures :
  1. 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)



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02314403


Locations
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United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
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Principal Investigator: Tatsuo Kawai, MD PhD Massachusetts General Hospital

Additional Information:
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Responsible Party: Tatsuo Kawai, MD, PhD, Associate Professor of Surgery, Harvard Medical School, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02314403     History of Changes
Other Study ID Numbers: MGH Tolerance Trial
First Posted: December 11, 2014    Key Record Dates
Last Update Posted: April 12, 2019
Last Verified: April 2019

Keywords provided by Tatsuo Kawai, MD, PhD, Massachusetts General Hospital:
ESRD

Additional relevant MeSH terms:
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Renal Insufficiency
Kidney Failure, Chronic
Kidney Diseases
Urologic Diseases
Renal Insufficiency, Chronic
Rituximab
Abatacept
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Immunosuppressive Agents