B Cell Induction in Pediatric Lung Transplantation

Patients who receive a lung transplant are at risk for rejection of the transplanted lung(s).
Rejection occurs when the new lung triggers the body's defense (immune) system. When the
immune system is triggered special cells are sent out to destroy the new lung and eventually
the lung may not be able to function as it should. These special cells include B cells. B
cells are an important part of the immune system and help the body fight infection. One way B
cells fight infection is by producing antibodies. B cells and the antibodies they produce are
involved in some kinds of rejection after organ transplantation.

Inclusion Criteria:

Enrollment:

1. Subject and/or parent guardian must be able to understand and provide informed
consent;

2. Candidate for a primary lung transplant (listed for lung transplant);

3. Female and male subjects with reproductive potential must agree to use FDA approved
methods of birth control for 12-months after completion of treatment.

4. Adequate bone marrow functions based on the following criteria:

- Absolute neutrophil count (ANC): >1000mm^3

- Platelets: >100,000/mm^3

- Hemoglobin: >7 gm/dL

- AST or ALT< 2x Upper Limit of Normal unless related to primary disease

Randomization:

Individuals who meet all of the following criteria are eligible for randomization:

1. Serum IgG immunoglobulin level greater than lower level of normal for age based on
local laboratory ranges or 400mg/dL within 90 days prior to randomization;

2. Female subjects of childbearing potential must have a negative pregnancy test within 4
hours of transplant;

3. Negative for Hepatitis B infection (if at time of transplant, participant does not
exhibit effective immunization, the participant should be re-tested).

Exclusion Criteria:

Enrollment:

Individuals who meet any of these criteria are not eligible for enrollment as study
participants:

1. Inability or unwillingness of a participant to give written informed consent or comply
with study protocol;

2. Multi-organ transplant;

3. Previous treatment with rituximab (Rituxan®);

4. History of severe allergic anaphylactic reactions to humanized or murine monoclonal
antibodies;

5. History of severe reaction to previous therapy with intravenous immunoglobulin (IVIG);

6. History of Burkholderia cenocepacia;

7. History of anti-CD20 therapy;

8. Persistent hypogammaglobulinemia (IgG < lower level of normal for age based on local
laboratory ranges or 400 gm/dL for >2 months) and/or IVIG replacement therapy;

9. Positive blood culture, sepsis or other disease process with hemodynamic instability
at time of enrollment;

10. Any history of serologic positivity to HIV, HBsAg, HBcAb and HCV Ab;

11. History of malignancy less than 2 years in 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);

12. Any condition, including psychiatric disorders, that in the opinion of the
investigator would interfere with the subject's ability to comply with study
requirements;

13. Participation in another investigational trial within 4 weeks of enrollment;

14. Currently lactating or plans to become pregnant during the timeframe of the study
follow-up period;

15. Past or current medical problems or findings from physical examination or laboratory
testing that are not listed above, which, in the opinion of the investigator, may pose
additional risks from participation in the study, may interfere with the participant's
ability to comply with study requirements or that may impact the quality or
interpretation of the data obtained from the study.

Randomization:

Individuals who meet any of these criteria are not eligible for randomization:

1. Use of an induction agent other than Thymoglobulin®;

2. Renal insufficiency requiring hemodialysis or ultrafiltration;

3. Inability to obtain intravenous access;

4. Positive blood culture, sepsis or other disease process with hemodynamic instability
at time of transplant;

5. Use of investigational agent(s) within 5 half-lives of the investigational drug or 4
weeks, whichever is longer;

6. Receipt of a MMR vaccine within 30 days prior to randomization;

7. Any condition that, in the opinion of the investigator, would interfere with the
subject's ability to comply with study requirements.