Clinical trial NCT01780454: Renal Allograft Tolerance Through Mixed Chimerism
Official title: Renal Allograft Tolerance Through Mixed Chimerism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: End Stage Renal Disease
Keywords: End Stage Renal Disease
Renal Transplant
Bone Marrow Transplant
Tolerance
Chimerism
ESRD
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2013-01-31
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: Successful Withdrawal of Immunosuppressive Therapy
timeFrame: 5 years
Secondary outcomes:
measure: Number of Participants With Engraftment Syndrome
timeFrame: 5 Years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: A. Benedict Cosimi, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: David Sachs, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.