Renal Allograft Tolerance Through Mixed Chimerism

NCT ID: NCT01780454

Last Updated: 2021-04-19

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

2 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-03-31

Study Completion Date

2020-06-30

Brief Summary

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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

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Conditions

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End Stage Renal Disease

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Combined Bone Marrow and Kidney Transplantation

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

Group Type EXPERIMENTAL

MEDI-507

Intervention Type DRUG

T-Cell Depleting Agent

Rituximab

Intervention Type DRUG

B-Cell Depleting Agent

Total Body Irradiation

Intervention Type RADIATION

Bone Marrow Depletion

Thymic Irradiation

Intervention Type RADIATION

Interventions

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MEDI-507

T-Cell Depleting Agent

Intervention Type DRUG

Rituximab

B-Cell Depleting Agent

Intervention Type DRUG

Total Body Irradiation

Bone Marrow Depletion

Intervention Type RADIATION

Thymic Irradiation

Intervention Type RADIATION

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Massachusetts General Hospital

OTHER

Sponsor Role lead

Responsible Party

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David Sachs M.D.

Director, Transplantation Biology Research Center

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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A. Benedict Cosimi, M.D.

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

David Sachs, M.D.

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

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Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 21666482 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21839648 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18216355 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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2013P000822

Identifier Type: -

Identifier Source: org_study_id

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