Prevention of Cardiac Allograft Vasculopathy Using Rituximab (Rituxan) Therapy in Cardiac Transplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01278745
First received: January 16, 2011
Last updated: February 28, 2014
Last verified: February 2014
  Purpose

All people who have a heart transplant are at risk for developing cardiac allograft vasculopathy (CAV). CAV means narrowing of the heart transplant vessels, which is associated with poor heart transplant function. People who develop antibodies after transplant have a higher risk of developing CAV. Infections, high cholesterol, and rejection also increase the risk of developing CAV. People who develop CAV usually have to receive another transplant. The purpose of this research study is to see if a study drug called Rituximab prevents CAV. Rituximab destroys certain types of white blood cells called B cells. B cells are important cells in the immune system that help the body fight infection by producing substances called antibodies. B cells and the antibodies they produce are also involved in some kinds of rejection after organ transplantation. Rituximab decreases the number of B cells in the blood and other tissues. The goal of this study is to determine if decreasing B cells with Rituximab can prevent injury to the transplanted heart.


Condition Intervention Phase
Cardiac Allograft Vasculopathy
Biological: Rituximab induction/conventional immunosuppression (tacrolimus, MMF, and steroid taper)
Drug: Rituximab placebo/conventional immunosuppression (tacrolimus, MMF, and steroid taper)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Prevention of Cardiac Allograft Vasculopathy Using Rituximab (Rituxan) Therapy in Cardiac Transplantation (CTOT-11)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Nominal change from baseline to 1 year in percent atheroma volume measured by intravascular ultrasound [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Post-transplant outcomes [ Time Frame: 6 months and 12 months post-transplant ] [ Designated as safety issue: Yes ]
    Outcomes include death, re-transplantation or re-listed for transplantation, number of episodes of biopsy proven acute rejection (BPAR) of any grade per subject, incidence of BPAR (any grade), Incidence of AMR, incidence of cellular rejection, incidence of any treated rejection, episodes of rejection associated with hemodynamic compromise (HDC)

  • Development of angiographically evident cardiac allograft vasculopathy [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: Yes ]
  • Post-transplant safety outcomes [ Time Frame: up to 12 months ] [ Designated as safety issue: Yes ]
    Serious infections requiring intravenous antimicrobial therapy, incidence of post-transplant lymphoproliferative disorder (PTLD), safety and tolerability of Rituximab

  • Development of post-transplant anti-HLA antibodies, including donor specific antibody [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Complement binding antibody [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • B cell depletion and recovery profile [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Measure indirect alloreactivity to donor HLA peptides in human heart transplant recipients using both fresh and frozen PBLs [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Develop a set of surrogate biomarkers of cellular, humoral, and molecular assays to monitor development of or protection from chronic allograft dysfunction, and explore mechanisms of action of novel therapies in humans [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Total atheroma volume change in average maximal intimal thickness, percentage of subjects with rapidly progressive CAV ≥0.5 mm in the first year [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Histological changes of antibody mediated rejection [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 300
Study Start Date: September 2011
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rituximab
Rituximab induction/conventional immunosuppression
Biological: Rituximab induction/conventional immunosuppression (tacrolimus, MMF, and steroid taper)
Placebo Comparator: Rituximab Placebo
Rituximab Placebo / conventional immunosuppression
Drug: Rituximab placebo/conventional immunosuppression (tacrolimus, MMF, and steroid taper)

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for Initial Enrollment:

  • Subject must be able to understand and provide informed consent;
  • Male or Female, 18 to 75 years of age;
  • Candidate for a primary heart transplant;
  • All previous PRA testing <30%LABScreen® PRA Class I and II with an MFI of <2000 or less than 10% by LABScreen® Single Antigen with an MFI <2000 at the time of transplant (Local HLA Center Testing);
  • Calculated GFR >40 mL/minute using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) ;
  • Female and male subjects with reproductive potential, must agree to use FDA approved methods of birth control for the duration of the study

Inclusion Criteria for Randomization / Post-transplant:

  • Negative PRA within 12 weeks prior to transplant (Local HLA Center Testing) using one of the following:

    1. One Lambda's LABScreen® Mixed Class I & II, or
    2. Less than 10% by One Lambda's LABScreen® PRA Class I and II with an MFI of <2000, or
    3. cPRA less than 10% by LABScreen® Single Antigen testing (Anti-HLA-A, B, DR, DQ). The antigens reported will include those with an MFI >2000.

      The Luminex Gen-Probe beads are equivalent to the One Lambda and may be used as an alternative ;

  • Calculated GFR >40mL/minute using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) at time of randomization ;
  • Serum IgG Immunoglobulin level greater than 500mg/dL within 90 days prior to randomization;
  • Negative test for HIV, HBsAg, HBcAb, and HCV Ab within 12 months prior to transplant. If documentation is not present to support that the testing was performed in the past 12 months, then a blood sample will be collected prior to transplant and sent for local testing. Results may be available after randomization. If positive result, the oversight committee will review the case and provide further recommendations.
  • Female subjects of childbearing potential must have a negative pregnancy test.

Exclusion Criteria for Enrollment:

  • Prior history of organ transplantation- Prior history of organ transplantation;
  • Previous treatment with Rituximab (MabThera® / Rituxan ®);
  • Intention to use any induction agents;
  • History of severe allergic anaphylactic reactions to humanized or murine monoclonal antibodies;
  • History of severe reaction to previous therapy with IVIG;
  • Lack of IV venous access;
  • Active systemic infection at time of enrollment;
  • Any history of Serologic positivity to HIV, HBsAg, HBcAb, and HCV Ab;
  • History of malignancy except adequately treated in-situ cervical carcinoma, or adequately treated basal or squamous cell carcinoma of the skin;
  • Any condition that, in the opinion of the investigator, would interfere with the subject's ability to comply with study requirements;
  • Use of other investigational drugs within 4 weeks of enrollment;
  • Currently breast-feeding or plans to become pregnant during the timeframe of the study follow-up period.

Exclusion Criteria for Randomization/Post-transplant:

  • Recipient of multiple solid organ or tissue transplants;
  • Previous treatment with Rituximab (MabThera® / Rituxan ®);
  • Use of any induction agents;
  • History of severe allergic anaphylactic reactions to humanized or murine monoclonal antibodies;
  • History of severe reaction to previous therapy with IVIG;
  • Lack of IV venous access;
  • Active systemic infection at time of randomization;
  • Any history of serologic positivity to HIV, HBsAg, HBcAb and HCV Ab;
  • Any condition that, in the opinion of the investigator, would interfere with the subject's ability to comply with study requirements;
  • Use of other investigational drugs within 4 weeks prior to randomization;
  • Receipt of a live vaccine within 30 days prior to randomization;
  • Currently breast-feeding or plans to become pregnant during the timeframe of the study follow-up period.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01278745

  Hide Study Locations
Locations
United States, California
Cedars Sinai Heart Institute Recruiting
Beverly Hills, California, United States, 90211
Contact: Tiffany Duan, RN, MN,CCRC    310-248-7129    Tiffany.Duan@cshs.org   
Principal Investigator: Jon Kobashigawa, MD         
Ronald Regan UCLA Medical Center Recruiting
Los Angeles, California, United States, 90095
Contact: Julie Chait, RN    310-206-4313    jchait@mednet.ucla.edu   
Principal Investigator: Gregg Fonarow, MD         
Stanford University/Palo Alto VA Recruiting
Palo Alto, California, United States, 94304
Contact: Son Nguyen    650-493-5000 ext 67199    Son.nguyen1@va.gov   
Sub-Investigator: Michael Pham, MD         
University of California San Francisco Recruiting
San Francisco, California, United States, 94143-0124
Contact: Julia Healy    415-514-1125    jhealy@medicine.ucsf.edu   
Principal Investigator: Teresa De Marco, MD         
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Helen Luikart    650-724-2883    luikart@stanford.edu   
Contact: Bitika Kohli    (650) 724-4740    bitika@stanford.edu   
Principal Investigator: Kiran Khush, MD         
United States, Connecticut
Yale University: New Haven Hospital Recruiting
New Haven, Connecticut, United States, 16510
Contact: Lynn Wilson    203-737-8871    lynn.wilson@ynhh.org   
Principal Investigator: D. Dries, MD         
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Rachel Zmora    312-695-1991    rzmora@nmh.org   
Principal Investigator: Robert Gordon, MD         
United States, Maryland
University of Maryland Recruiting
Baltimore, Maryland, United States, 21201
Contact: Dana Beach    410-328-0993    dbeach@smail.umaryland.edu   
Principal Investigator: Erika Feller, MD         
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Eileen Mann, RN    617-525-7073    emann@partners.org   
Principal Investigator: Michael Givertz, MD         
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Sandy deBronkart, RN    617-726-2631    sdebronkart@partners.org   
Principal Investigator: Joren C Madsen, MD, DPhil         
Tufts Medical Center Recruiting
Boston, Massachusetts, United States, 02111
Contact: Ryan O'Kelly    617-636-4990    ROkelly@tuftsmedicalcenter.org   
Principal Investigator: David DeNofrio, MD         
United States, Minnesota
Minneapolis Heart Institute Recruiting
Minneapolis, Minnesota, United States, 55407
Contact: Susab Gjersik    612-863-1674    susan.falk@allina.com   
Principal Investigator: David Feldman, MD, PhD         
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Matt Larson    612-625-9455    larso342@umn.edu   
Contact: Aimee Hamel    (612) 626-3712    ahamel@umn.edu   
Principal Investigator: Monica Colvin-Adams, MD         
United States, New York
Mount Sinai School of Medicine Recruiting
New York, New York, United States, 10029
Contact: Rashid Ahmed    212-241-3453    rashid.ahmed@mountsinai.org   
Principal Investigator: Sean Pinney, MD         
Columbia University Medical Center Not yet recruiting
New York, New York, United States, 10032`
Contact: Mary Marks, RN    212-305-1368    mc2228@columbia.edu   
Principal Investigator: Donna Mancini, MD         
United States, Ohio
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: Barbara Gus, RN    216-445-6552    GusB@ccf.org   
Principal Investigator: Randall Starling, MD         
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Faith Pickering    215-662-4214    faith.pickering@uphs.upenn.edu   
Contact: Marisa Konig    (215) 615-3236    marisa.konig@uphs.upenn.edu   
Principal Investigator: Lee Goldberg, MD         
Drexel University College of Medicine Recruiting
Philadelphia, Pennsylvania, United States, 19102
Contact: Colleen Poisker, RN    215-762-8512    Cpoisker@drexelmed.edu   
Contact: Janet Matthews    (215) 762-8563    Janet.matthews@drexelmed.edu   
Principal Investigator: Howard J. Eisen, MD         
Allegheny General Hospital Recruiting
Pittsburgh, Pennsylvania, United States, 15212
Contact: Pranav Ravi    412-359-6691    pravi@wpahs.org   
Contact: Joseph Carothers    412-359-4156    jcarothe@wpahs.org   
Principal Investigator: Srinivas Murali, MD         
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Theodora Hollifield    843-876-5011    russelcm@musc.edu   
Principal Investigator: Adrian Van Bakel, MD         
United States, Texas
Medical City Dallas Hospital/CRSTI Recruiting
Dallas, Texas, United States, 75230
Contact: Tina Worley, RN    972-566-4083    tworley@crsti.org   
Principal Investigator: Judson Hunt, MD         
The Methodist Hospital Not yet recruiting
Houston, Texas, United States, 77030
Contact: Anna Rodriguez    713-441-4536    amrodriguez2@tmhs.org   
Principal Investigator: Arvind Bhimaraj, MD         
United States, Utah
Intermountain Medical Center Recruiting
Murray, Utah, United States, 84157
Contact: Joe Tuinei, BS    801-507-4796    joe.tuinei@imail.org   
Principal Investigator: A G Kfoury, MD         
University of Utah Recruiting
Salt Lake City, Utah, United States, 84132-2401
Contact: Melissa Whipple    801-587-9048    melissa.whipple@hsc.utah.edu   
Principal Investigator: Josef Stehlik, MD         
United States, Virginia
Virginia Commonwealth University Not yet recruiting
Richmond, Virginia, United States, 23298
Contact: J Hager, MPH    804-628-2520    jhager@mcvh-vcu.edu   
Principal Investigator: Keyur Shah, MD         
United States, Wisconsin
University of Wisconsin Recruiting
Madison, Wisconsin, United States, 53792
Contact: Travis Doran    608-265-6417    tadoran@clinicaltrials.wisc.edu   
Principal Investigator: Maryl Johnson, MD         
Sponsors and Collaborators
Investigators
Study Chair: Randall Starling, MD The Cleveland Clinic
Principal Investigator: Mohamed Sayegh, MD Brigham and Women's Hospital/Harvard
Study Chair: Anil Chandraker, MD Brigham and Women's Hospital/Harvard
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01278745     History of Changes
Other Study ID Numbers: DAIT CTOT-11
Study First Received: January 16, 2011
Last Updated: February 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Tacrolimus
Rituximab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 26, 2014