Renal Allograft Tolerance Through Mixed Chimerism

NCT01780454 | Completed Phase 1 Results

• 1 other identifier: 2013P000822
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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

Conditions

End Stage Renal Disease

Keywords

End Stage Renal Disease; Renal Transplant; Bone Marrow Transplant; Tolerance; Chimerism; ESRD

Outcome Measures

Primary Outcomes (1)

• 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"

  5 years

Secondary Outcomes (1)

• Number of Participants With Engraftment Syndrome

  5 Years

Study Arms (1)

Combined Bone Marrow and Kidney Transplantation

EXPERIMENTAL

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

Drug: MEDI-507; Drug: Rituximab; Radiation: Total Body Irradiation; Radiation: Thymic Irradiation

Interventions

MEDI-507 DRUG

T-Cell Depleting Agent

Combined Bone Marrow and Kidney Transplantation

Rituximab DRUG

B-Cell Depleting Agent

Combined Bone Marrow and Kidney Transplantation

Total Body Irradiation RADIATION

Bone Marrow Depletion

Combined Bone Marrow and Kidney Transplantation

Thymic Irradiation RADIATION

Combined Bone Marrow and Kidney Transplantation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (3)

• 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.

  PMID: 21666482 BACKGROUND

• 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.

  PMID: 21839648 BACKGROUND

• 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.

  PMID: 18216355 BACKGROUND

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

siplizumab; Rituximab; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Investigative Techniques

Results Point of Contact

• Title: Dr. David Sachs
• Organization: Massachusetts General Hospital

David.Sachs@tbrc.mgh.harvard.edu

617-726-4065

Study Officials

• A. Benedict Cosimi, M.D.

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• David Sachs, M.D.

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Transplantation Biology Research Center

Study Record Dates

• First Submitted: January 29, 2013
• First Posted: January 31, 2013
• Study Start: March 1, 2013
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2020
• Last Updated: April 19, 2021
• Results First Posted: September 23, 2020

Record last verified: 2021-03

Locations

US (1)