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B Cell Induction in Pediatric Lung Transplantation

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ClinicalTrials.gov Identifier: NCT02266888
Recruitment Status : Active, not recruiting
First Posted : October 17, 2014
Last Update Posted : November 1, 2018
Sponsor:
Collaborator:
Clinical Trials in Organ Transplantation in Children
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief 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.

Condition or disease Intervention/treatment Phase
Lung Transplant Biological: Rituximab (Rituxan®) Biological: Placebo Phase 2

Detailed Description:
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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: B Cell Targeted Induction to Improve Outcomes in Pediatric Lung Transplantation (CTOTC-08)
Actual Study Start Date : January 22, 2015
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Rituximab

Arm Intervention/treatment
Experimental: Rituximab Induction
Rituximab (Rituxan®) Induction Therapy Plus Standard of Care Immunosuppression (thymoglobulin induction, tacrolimus or equivalent, MMF or equivalent, and steroids)
Biological: 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).
Other Name: Rituxan®

Placebo Comparator: Placebo Induction
Placebo Induction Therapy Plus Standard of Care Immunosuppression (Thymoglobulin® induction, tacrolimus or equivalent, MMF or equivalent, and steroids)
Biological: Placebo
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).




Primary Outcome Measures :
  1. Earliest time to Chronic Allograft Dysfunction [ Time Frame: From 12 months (1 year) to 54 months (4.5 years) post-transplant ]
  2. Earliest time to listing for retransplantation [ Time Frame: From 12 months (1 year) to 54 months (4.5 years) post-transplant ]
  3. Time to Death [ Time Frame: From 12 months (1 year) to 54 months (4.5 years) post-transplant ]

Secondary Outcome Measures :
  1. Incidence of chronic allograft dysfunction [ Time Frame: From 12 months (1 year) to 54 months (4.5 years) post-transplant ]
  2. Incidence of relisting for retransplant [ Time Frame: From 12 months (1 year) to 54 months (4.5 years) post-transplant ]
  3. Incidence of death [ Time Frame: From 12 months (1 year) to 54 months (4.5 years) post-transplant ]
  4. Incidence of Primary Graft Dysfunction [ Time Frame: From 12 months (1 year) to 54 months (4.5 years) post-transplant ]
  5. Incidence of Grade A Acute Rejection [ Time Frame: Up to 24 months (2 years) post-transplant ]
  6. Incidence of Antibody Mediated Rejection [ Time Frame: Up to 24 months (2 years) post-transplant ]
  7. Incidence of tacrolimus variability threshold (TVT) [ Time Frame: Up to 24 months (2 years) post-transplant ]
  8. Percentage of participants meeting tacrolimus variability threshold who complete tacrolimus variability intervention [ Time Frame: From 12 months (1 year) to 54 months (4.5 years) post-transplant ]
  9. Magnitude of change in standard deviation of tacrolimus levels following intervention [ Time Frame: From 12 months (1 year) to 54 months (4.5 years) post-transplant ]
  10. Incidence and severity of infection episodes [ Time Frame: From 12 months (1 year) to 54 months (4.5 years) post-transplant ]
  11. Incidence of all adverse events related to rituximab [ Time Frame: From 12 months (1 year) to 54 months (4.5 years) post-transplant ]


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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02266888


Locations
United States, California
Stanford University
Palo Alto, California, United States, 94305
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, Missouri
Washington University
Saint Louis, Missouri, United States, 63110
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Clinical Trials in Organ Transplantation in Children
Investigators
Study Chair: Stuart Sweet, M.D., Ph.D. Washington University Medical Center: Department of Pediatrics, Division of Allergy, Immunology and Pulmonary Medicine
Study Chair: Lara Danziger-Isakov, M.D., M.P.H. Cincinnati Children's Hospital: Division of Infectious Diseases

Additional Information:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02266888     History of Changes
Other Study ID Numbers: DAIT CTOTC-08
First Posted: October 17, 2014    Key Record Dates
Last Update Posted: November 1, 2018
Last Verified: October 2018

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
B cells
lung transplant recipient
rituximab
placebo
standard of care

Additional relevant MeSH terms:
Rituximab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents