B Cell Induction in Pediatric Lung Transplantation

NCT02266888 | Completed Phase 2 Results DMC

• 2 other identifiers: DAIT CTOTC-08NIAID CRMS ID#: 20181
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 7

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.

Conditions

Lung Transplant

Keywords

B cells; lung transplant recipient; rituximab; placebo; standard of care

Outcome Measures

Primary Outcomes (1)

• Earliest Time to Any of the Following Events: Chronic Allograft Dysfunction, Listed for Retransplant or Death

  This composite outcome measures is defined as the earliest time post-transplant to any of the following events during the follow-up period: * Chronic Allograft Dysfunction (defined as the occurrence of confirmed Bronchiolitis Obliterans Syndrome (BOS) grade 0-p or higher or a diagnosis of Obliterative Bronchiolitis (OB)), * Listed for re-transplant (e.g., second lung transplant), or * Death.

  Up to 35 months post-transplant

Secondary Outcomes (12)

• Percent of Participants Diagnosed With Chronic Allograft Dysfunction

  Up to 35 months post-transplant

• Percent of Participants Listed for Re-Transplant During the Study Follow-Up Period

  Up to 35 months post-transplant

• Percent of Participants Who Died During the Study Follow-Up Period

  Up to 35 months post-transplant

• Percent of Participants With Primary Graft Dysfunction (PGD)

  Up to 72 hours post-transplant

• Percent of Participants With Occurrence of Grade A Acute Rejection

  Up to 24 months post-transplant

Study Arms (2)

Rituximab Induction

EXPERIMENTAL

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

Biological: Rituximab (Rituxan®)

Placebo Induction

PLACEBO COMPARATOR

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

Biological: Placebo

Interventions

Rituximab (Rituxan®) BIOLOGICAL

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

Also known as: Rituxan®

Rituximab Induction

Placebo 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).

Placebo Induction

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Enrollment:
• Subject and/or parent guardian must be able to understand and provide informed consent;
• Candidate for a primary lung transplant (listed for lung transplant);
• Female and male subjects with reproductive potential must agree to use FDA approved methods of birth control for 12-months after completion of treatment.
• 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:
• 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;
• Female subjects of childbearing potential must have a negative pregnancy test within 4 hours of transplant;
• Negative for Hepatitis B infection (if at time of transplant, participant does not exhibit effective immunization, the participant should be re-tested).

You may not qualify if:

• Enrollment:
• Individuals who meet any of these criteria are not eligible for enrollment as study participants:
• Inability or unwillingness of a participant to give written informed consent or comply with study protocol;
• Multi-organ transplant;
• Previous treatment with rituximab (Rituxan®);
• History of severe allergic anaphylactic reactions to humanized or murine monoclonal antibodies;
• History of severe reaction to previous therapy with intravenous immunoglobulin (IVIG);
• History of Burkholderia cenocepacia;
• History of anti-CD20 therapy;
• 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;
• Positive blood culture, sepsis or other disease process with hemodynamic instability at time of enrollment;
• Any history of serologic positivity to HIV, HBsAg, HBcAb and HCV Ab;
• 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);
• Any condition, including psychiatric disorders, that in the opinion of the investigator would interfere with the subject's ability to comply with study requirements;
• Participation in another investigational trial within 4 weeks of enrollment;

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Clinical Trials in Organ Transplantation in Children: collaborator
• Rho Federal Systems Division, Inc.: collaborator

Study Sites (7)

Stanford University

Palo Alto, California, 94305, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Related Publications (2)

• 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.

  PMID: 34599540 RESULT

• 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.

  PMID: 33752251 RESULT

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)
• Clinical Trials in Organ Transplantation in Children (CTOT-C)

MeSH Terms

Interventions

Rituximab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Director, Clinical Research Operations Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• 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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2014
• First Posted: October 17, 2014
• Study Start: January 22, 2015
• Primary Completion: June 30, 2019
• Study Completion: June 30, 2019
• Last Updated: October 26, 2021
• Results First Posted: July 16, 2020

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share
• Time Frame: On average, within 24 months after database lock for the trial.
• Access Criteria: Open access.

Locations

US (7)