B Cell Induction in Pediatric Lung Transplantation
Condition: Lung Transplant
Intervention: Rituximab (Rituxan®); Placebo
Intervention description: 2 Doses: 375 mg/m^2 on Day 0 (within 12 hours of return to ICU following transplant) and Day 12 (+/-2 days).; Placebo for Rituximab (Rituxan®). 2 Doses: 375 mg/m^2 on Day 0 (within 12 hours of return to ICU following transplant) and Day 12 (+/-2 days).
Intervention MeSH terms: Rituximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 45.0
Sex: All
Maximum age: 21 Years
Healthy volunteers: No
Keywords: B cells; lung transplant recipient; rituximab; placebo; standard of care

Summary:

      In this study, doctors are trying to see if a study drug called rituximab (Rituxan®) will
      lower the number of B cells in the body. Doctors are also trying to see if decreasing B cells
      with rituximab (Rituxan®) can prevent injury to the transplanted lung. This treatment has
      been studied in other types of solid organ transplants.
    

Eligibility criteria:

        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.