B Cell Induction in Pediatric Lung Transplantation

NCT ID: NCT02266888

Last Updated: 2021-10-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-22
• Study Completion Date: 2019-06-30

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.

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.

Conditions

Lung Transplant

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Rituximab Induction

Rituximab (Rituxan®) Induction Therapy Plus Standard of Care Immunosuppression (thymoglobulin induction, tacrolimus or equivalent, mycophenolate mofetil (MMF) or equivalent, and steroids)

Group Type: EXPERIMENTAL

Rituximab (Rituxan®)

Intervention Type: BIOLOGICAL

2 Doses: 375 mg/m\^2 on Day 0 (within 12 hours of return to ICU following transplant) and Day 12 (+/-2 days).

Placebo Induction

Placebo Induction Therapy Plus Standard of Care Immunosuppression (Thymoglobulin® induction, tacrolimus or equivalent, mycophenolate mofetil (MMF) or equivalent, and steroids)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

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).

Interventions

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 Type: 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).

Intervention Type: BIOLOGICAL

Other Intervention Names

Rituxan®

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.

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clinical Trials in Organ Transplantation in Children

OTHER

Sponsor Role: collaborator

Rho Federal Systems Division, Inc.

INDUSTRY

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stuart Sweet, M.D., Ph.D.

Role: STUDY_CHAIR

Washington University Medical Center: Department of Pediatrics, Division of Allergy, Immunology and Pulmonary Medicine

Lara Danziger-Isakov, M.D., M.P.H.

Role: STUDY_CHAIR

Cincinnati Children's Hospital: Division of Infectious Diseases

Locations

Stanford University

Palo Alto, California, United States

Children's Hospital Boston

Boston, Massachusetts, United States

Washington University

St Louis, Missouri, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Texas Children's Hospital

Houston, Texas, United States

Countries

United States

References

Sweet SC, Armstrong B, Blatter J, Chin H, Conrad C, Goldfarb S, Hayes D Jr, Heeger PS, Lyou V, Melicoff-Portillo E, Mohanakumar T, Odim J, Ravichandran R, Schecter M, Storch GA, Visner G, Williams NM, Danziger-Isakov L. CTOTC-08: A multicenter randomized controlled trial of rituximab induction to reduce antibody development and improve outcomes in pediatric lung transplant recipients. Am J Transplant. 2022 Jan;22(1):230-244. doi: 10.1111/ajt.16862. Epub 2021 Nov 5.

Reference Type: RESULT

PMID: 34599540 (View on PubMed)

Duncan-Park S, Dunphy C, Becker J, D'Urso C, Annunziato R, Blatter J, Conrad C, Goldfarb SB, Hayes D Jr, Melicoff E, Schecter M, Visner G, Armstrong B, Chin H, Kesler K, Williams NM, Odim JN, Sweet SC, Danziger-Isakov L, Shemesh E. Remote intervention engagement and outcomes in the Clinical Trials in Organ Transplantation in Children consortium multisite trial. Am J Transplant. 2021 Sep;21(9):3112-3122. doi: 10.1111/ajt.16567. Epub 2021 Apr 12.

Reference Type: RESULT

PMID: 33752251 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases (NIAID)

https://www.niaid.nih.gov/about/dait

Division of Allergy, Immunology, and Transplantation (DAIT)

http://www.ctotc.org/

Clinical Trials in Organ Transplantation in Children (CTOT-C)

Other Identifiers

NIAID CRMS ID#: 20181

Identifier Type: OTHER

Identifier Source: secondary_id

DAIT CTOTC-08

Identifier Type: -

Identifier Source: org_study_id