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Renal Allograft Tolerance Through Mixed Chimerism

Primary Purpose

End Stage Renal Disease

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
MEDI-507
Rituximab
Total Body Irradiation
Thymic Irradiation
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for End Stage Renal Disease focused on measuring End Stage Renal Disease, Renal Transplant, Bone Marrow Transplant, Tolerance, Chimerism, ESRD

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  • Male or female 18-60 years of age
  • Candidate for a living-donor renal allograft with a one haplotype identical donor identified.
  • First or second transplant with either a living donor or cadaveric transplant as the first transplant.
  • Positive serologic testing for EBV indicating past exposure.

Key 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)
  • Positive testing for: HIV, hepatitis B core antigen, or hepatitis C virus or positivity for hepatitis B surface antigen.
  • Cardiac ejection fraction < 40% or clinical evidence of insufficiency.
  • 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 nonproliferative glomerulonephritis).
  • Prior dose-limiting radiation therapy.
  • Abnormal (>2 times lab normal) values for (a) liver function chemistries (ALT, AST, AP), (b) bilirubin, (c) coagulation studies (PT, PTT).
  • 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

Conditioning regimen consisting of Rituximab, MEDI-507, Total Body Irradiation, Thymic Irradiation followed by simultaneous bone marrow and kidney transplantation

Outcomes

Primary Outcome Measures

Successful Withdrawal of Immunosuppressive Therapy
The primary endpoint is induction of transient mixed chimerism and renal allograft tolerance without "engraftment syndrome" or "acute kidney injury"

Secondary Outcome Measures

Number of Participants With Engraftment Syndrome
Constellation of symptoms known "Engraftment Syndrome"

Full Information

First Posted
January 29, 2013
Last Updated
March 19, 2021
Sponsor
Massachusetts General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01780454
Brief Title
Renal Allograft Tolerance Through Mixed Chimerism
Official Title
Renal Allograft Tolerance Through Mixed Chimerism
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
March 2013 (undefined)
Primary Completion Date
June 2018 (Actual)
Study Completion Date
June 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital

4. Oversight

Data Monitoring Committee
No

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
End Stage Renal Disease
Keywords
End Stage Renal Disease, Renal Transplant, Bone Marrow Transplant, Tolerance, Chimerism, ESRD

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
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
Conditioning regimen consisting of Rituximab, MEDI-507, Total Body Irradiation, Thymic Irradiation followed by simultaneous bone marrow and kidney transplantation
Intervention Type
Drug
Intervention Name(s)
MEDI-507
Intervention Description
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 Description
Bone Marrow Depletion
Intervention Type
Radiation
Intervention Name(s)
Thymic Irradiation
Primary Outcome Measure Information:
Title
Successful Withdrawal of Immunosuppressive Therapy
Description
The primary endpoint is induction of transient mixed chimerism and renal allograft tolerance without "engraftment syndrome" or "acute kidney injury"
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Number of Participants With Engraftment Syndrome
Description
Constellation of symptoms known "Engraftment Syndrome"
Time Frame
5 Years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Male or female 18-60 years of age Candidate for a living-donor renal allograft with a one haplotype identical donor identified. First or second transplant with either a living donor or cadaveric transplant as the first transplant. Positive serologic testing for EBV indicating past exposure. Key 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) Positive testing for: HIV, hepatitis B core antigen, or hepatitis C virus or positivity for hepatitis B surface antigen. Cardiac ejection fraction < 40% or clinical evidence of insufficiency. 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 nonproliferative glomerulonephritis). Prior dose-limiting radiation therapy. Abnormal (>2 times lab normal) values for (a) liver function chemistries (ALT, AST, AP), (b) bilirubin, (c) coagulation studies (PT, PTT). 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
A. Benedict Cosimi, M.D.
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David Sachs, M.D.
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

Citations:
PubMed Identifier
21666482
Citation
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. doi: 10.1097/MOT.0b013e3283484b2c.
Results Reference
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PubMed Identifier
21839648
Citation
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. doi: 10.1016/j.smim.2011.07.001. Epub 2011 Aug 11.
Results Reference
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PubMed Identifier
18216355
Citation
Kawai T, Cosimi AB, Spitzer TR, Tolkoff-Rubin N, Suthanthiran M, Saidman SL, Shaffer J, Preffer FI, Ding R, Sharma V, Fishman JA, Dey B, Ko DS, Hertl M, Goes NB, Wong W, Williams WW Jr, Colvin RB, Sykes M, Sachs DH. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2008 Jan 24;358(4):353-61. doi: 10.1056/NEJMoa071074.
Results Reference
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Renal Allograft Tolerance Through Mixed Chimerism

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