Back to resultsRenal Allograft Tolerance Through Mixed Chimerism (Belatacept)
Primary Purpose
Kidney Failure, Chronic, Renal Insufficiency
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Belatacept
ATG
Rituximab
Total Body Irradiation
Thymic Irradiation
Combined Bone Marrow/Kidney Transplantation
Sponsored by
About this trial
This is an interventional treatment trial for Kidney Failure, Chronic focused on measuring ESRD
Eligibility 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.
Sites / Locations
- Massachusetts General Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Combined Bone Marrow and Kidney Transplantation
Arm Description
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.
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
Full Information
NCT ID
NCT02314403
First Posted
December 5, 2014
Last Updated
October 4, 2021
Sponsor
Massachusetts General Hospital
1. Study Identification
Unique Protocol Identification Number
NCT02314403
Brief Title
Renal Allograft Tolerance Through Mixed Chimerism (Belatacept)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
February 2015 (undefined)
Primary Completion Date
March 2021 (Actual)
Study Completion Date
July 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Failure, Chronic, Renal Insufficiency
Keywords
ESRD
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Combined Bone Marrow and Kidney Transplantation
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Belatacept
Intervention Description
A selective T-cell (lymphocyte) costimulation blocker
Intervention Type
Drug
Intervention Name(s)
ATG
Intervention Description
A T-Cell Depleting Agent
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
B-Cell Depleting Agent
Intervention Type
Radiation
Intervention Name(s)
Total Body Irradiation
Intervention Type
Radiation
Intervention Name(s)
Thymic Irradiation
Intervention Type
Procedure
Intervention Name(s)
Combined Bone Marrow/Kidney Transplantation
Primary Outcome Measure Information:
Title
Number of Participants With Successful Withdrawal of Immunosuppression
Description
The Primary Outcome is: The induction of transient mixed chimerism and renal allograft tolerance (24 consecutive months off of immunosuppression)
Time Frame
5 Years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tatsuo Kawai, MD PhD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.ncbi.nlm.nih.gov/pubmed/21666482?dopt=Abstract
Description
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.
URL
http://www.ncbi.nlm.nih.gov/pubmed/21839648?dopt=Abstract
Description
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.
URL
http://www.ncbi.nlm.nih.gov/pubmed/18216355?dopt=Abstract
Description
Kawai T, (et.al.) HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2008 Jan 24;358(4):353-61.
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Renal Allograft Tolerance Through Mixed Chimerism (Belatacept)
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