Prevention of Cardiac Allograft Vasculopathy Using Rituximab (Rituxan) Therapy in Cardiac Transplantation
Condition: Cardiac Allograft Vasculopathy; Heart Transplant Recipients
MeSH terms: Vascular Diseases
Intervention: Rituximab induction/conventional immunosuppression (tacrolimus, MMF, and steroid taper); Rituximab placebo/conventional immunosuppression (tacrolimus, MMF, and steroid taper)
Intervention MeSH terms: Rituximab; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 362.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: cardiac allograft vasculopathy (CAV); prevention; cardiac transplantation; rituximab

Summary:

      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.
    

Eligibility 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 (e.g., listed for heart transplant only);

          -  Historical panel reactive antibodies (PRA) less than 30%;

          -  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:

          -  One Lambda's LABScreen® Mixed Class I & II (presence or absence), or

          -  Less than 10% by One Lambda's LABScreen® PRA Class I and II with an MFI of <2000, or

          -  Calculated panel reactive antibodies (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 CKD-EPI at time of randomization;

          -  Serum immunoglobulin G (IgG) 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;

          -  Previous treatment with Rituximab (MabThera® / Rituxan ®);

          -  Transplant physician 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;

          -  Active systemic infection at time of enrollment;

          -  Any history of serologic positivity to HIV, HBsAg, HBcAb, and HCV Ab;

          -  History of less than 5 years remission of malignancy. Any history of adequately
             treated in-situ cervical carcinoma, or adequately treated basal or squamous cell
             carcinoma of the skin will be permitted;

          -  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.