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

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.