Renal Allograft Tolerance Through Mixed Chimerism

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01780454
• Collaborator: (none)
• Enrollment: 2
• Location: 1
• Arm: 1
• Duration (Months): 87
• Patients Per Site Per Month: 0

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
End Stage Renal Disease	Drug: MEDI-507; Drug: Rituximab; Radiation: Total Body Irradiation; Radiation: Thymic Irradiation	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Renal Allograft Tolerance Through Mixed Chimerism
• Study Start Date: Mar 1, 2013
• Actual Primary Completion Date: Jun 1, 2018
• Actual Study Completion Date: Jun 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: MEDI-507; T-Cell Depleting Agent; Drug: Rituximab; B-Cell Depleting Agent; Radiation: Total Body Irradiation; Bone Marrow Depletion; Radiation: Thymic Irradiation

Outcome Measures

Primary Outcome Measures

1. Successful Withdrawal of Immunosuppressive Therapy [5 years]

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

Secondary Outcome Measures

1. Number of Participants With Engraftment Syndrome [5 Years]

   Constellation of symptoms known "Engraftment Syndrome"

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital

Investigators

• Principal Investigator: A. Benedict Cosimi, M.D., Massachusetts General Hospital
• Principal Investigator: David Sachs, M.D., Massachusetts General Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 27, 2014

More Information

Publications

• 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. Review.
• 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.
• 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. Review.

• Responsible Party: David Sachs M.D., Director, Transplantation Biology Research Center, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01780454
• Other Study ID Numbers: 2013P000822
• First Posted: Jan 31, 2013
• Last Update Posted: Apr 19, 2021
• Last Verified: Mar 1, 2021

• Keywords provided by David Sachs M.D., Director, Transplantation Biology Research Center, Massachusetts General Hospital: End Stage Renal Disease; Renal Transplant; Bone Marrow Transplant; Tolerance; Chimerism; ESRD
• Additional relevant MeSH terms: Kidney Diseases; Kidney Failure, Chronic; Rituximab

Study Results

Participant Flow

Arm/Group Title	Combined Bone Marrow and Kidney Transplantation
Arm/Group Description	Conditioning regimen consisting of Rituximab, MEDI-507, Total Body Irradiation, Thymic Irradiation followed by simultaneous bone marrow and kidney transplantation MEDI-507: T-Cell Depleting Agent Rituximab: B-Cell Depleting Agent Total Body Irradiation: Bone Marrow Depletion Thymic Irradiation
Period Title: Overall Study
STARTED	2
COMPLETED	2
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Combined Bone Marrow and Kidney Transplantation
Arm/Group Description	Conditioning regimen consisting of Rituximab, MEDI-507, Total Body Irradiation, Thymic Irradiation followed by simultaneous bone marrow and kidney transplantation MEDI-507: T-Cell Depleting Agent Rituximab: B-Cell Depleting Agent Total Body Irradiation: Bone Marrow Depletion Thymic Irradiation
Overall Participants	2
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	2 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 50%
Not Hispanic or Latino	1 50%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	1 50%
More than one race	0 0%
Unknown or Not Reported	1 50%
Region of Enrollment (participants) [Number]
United States	2 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combined Bone Marrow and Kidney Transplantation
Arm/Group Description	Conditioning regimen consisting of Rituximab, MEDI-507, Total Body Irradiation, Thymic Irradiation followed by simultaneous bone marrow and kidney transplantation MEDI-507: T-Cell Depleting Agent Rituximab: B-Cell Depleting Agent Total Body Irradiation: Bone Marrow Depletion Thymic Irradiation
Measure Participants	2
Count of Participants [Participants]	2 100%

2. Secondary Outcome

Title	Number of Participants With Engraftment Syndrome
Description	Constellation of symptoms known "Engraftment Syndrome"
Time Frame	5 Years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combined Bone Marrow and Kidney Transplantation
Arm/Group Description	Conditioning regimen consisting of Rituximab, MEDI-507, Total Body Irradiation, Thymic Irradiation followed by simultaneous bone marrow and kidney transplantation MEDI-507: T-Cell Depleting Agent Rituximab: B-Cell Depleting Agent Total Body Irradiation: Bone Marrow Depletion Thymic Irradiation
Measure Participants	2
Count of Participants [Participants]	2 100%

Adverse Events

Time Frame	5 years
Arm/Group Title	Combined Bone Marrow and Kidney Transplantation
Arm/Group Description	Conditioning regimen consisting of Rituximab, MEDI-507, Total Body Irradiation, Thymic Irradiation followed by simultaneous bone marrow and kidney transplantation MEDI-507: T-Cell Depleting Agent Rituximab: B-Cell Depleting Agent Total Body Irradiation: Bone Marrow Depletion Thymic Irradiation
All Cause Mortality
	Combined Bone Marrow and Kidney Transplantation
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Serious Adverse Events
	Combined Bone Marrow and Kidney Transplantation
	Affected / at Risk (%)	# Events
Total	1/2 (50%)
Gastrointestinal disorders
Dehydration	1/2 (50%)	1
Other (Not Including Serious) Adverse Events
	Combined Bone Marrow and Kidney Transplantation
	Affected / at Risk (%)	# Events
Total	2/2 (100%)
Blood and lymphatic system disorders
Neutropenia	2/2 (100%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.