Soluble Tumor Necrosis Factor Receptor: Enbrel® (Etanercept) for the Treatment of Acute Non-Infectious Pulmonary Dysfunction (Idiopathic Pneumonia Syndrome) Following Allogeneic Stem Cell Transplantation
I. Determine the response rate, defined as survival and complete discontinuation of
supplemental oxygen at day 28, in pediatric patients with acute noninfectious pulmonary
dysfunction (idiopathic pneumonia syndrome [IPS]) after undergoing allogeneic stem cell
transplantation treated with etanercept.
I. Estimate the day 56 survival rate in patients treated with this drug. II. Determine the
overall survival distribution in patients treated with this drug.
III. Determine the pulmonary response, as defined as the time to discontinuation of
supplemental oxygen, in patients treated with this drug.
IV. Evaluate the toxicity of etanercept therapy in patients with IPS. V. Evaluate levels of
pro-inflammatory cytokines, in both bronchoalveolar lavage (BAL) fluid and serum, in
patients with IPS.
VI. Describe C-reactive protein (CRP) levels at baseline, day 7, 14, 21, and 28 and their
association with response in patients with IPS.
OUTLINE: This is an open-label, nonrandomized, multicenter study.
Patients receive etanercept IV over 30 minutes on day 0 and subcutaneously on days 3, 7, 10,
14, 17, 21, and 24. Treatment continues in the absence of an infectious pathogen, disease
progression, or unacceptable toxicity. Patients also receive methylprednisolone (or
corticosteroid equivalent) IV on days 0-2 and then orally with a taper until day 56.
After completion of study treatment, patients are followed periodically for 5 years.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of patients with IPS who respond to etanercept and corticosteroid therapy plus complete discontinuation all supplemental oxygen support
The "time to response" will be defined as the first of 3 consecutive days in which all supplemental oxygen has been discontinued. Subjects who discontinue supplemental oxygen support during the study period (Day 0-28), but subsequently require re-institution of supplemental oxygen, will still be deemed as responders provided they meet the response criteria listed above. The median duration of time (number of days) that a patient requires supplemental oxygen will be determined using standard descriptive statistics, or Kaplan-Meier methods in the case of censoring.
At day 28
Children's Oncology Group
United States: Institutional Review Board
|Johns Hopkins University||Baltimore, Maryland 21205|
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|Indiana University Cancer Center||Indianapolis, Indiana 46202-5265|
|Medical University of South Carolina||Charleston, South Carolina 29425-0721|
|Midwest Children's Cancer Center||Milwaukee, Wisconsin 53226|
|Loma Linda University Medical Center||Loma Linda, California 92354|
|New York Medical College||Valhalla, New York 10595|
|University of Nebraska Medical Center||Omaha, Nebraska 68198-3330|
|Hackensack University Medical Center||Hackensack, New Jersey 07601|
|Children's National Medical Center||Washington, District of Columbia 20010-2970|
|All Children's Hospital||St. Petersburg, Florida 33701|
|Methodist Children's Hospital of South Texas||San Antonio, Texas 78229-3993|
|Children's Hospital of Pittsburgh of UPMC||Pittsburgh, Pennsylvania 15213|
|University of Alabama at Birmingham||Birmingham, Alabama 35294-3300|
|Indiana University Medical Center||Indianapolis, Indiana 46202|
|University of Texas Southwestern Medical Center||Dallas, Texas|
|Oregon Health and Science University||Portland, Oregon 97201|
|Seattle Children's Hospital||Seattle, Washington 98105|
|Childrens Memorial Hospital||Chicago, Illinois 60614|
|Columbia University Medical Center||New York, New York 10032|
|Cook Children's Medical Center||Fort Worth, Texas 76104|
|Children's Oncology Group||Arcadia, California 91006-3776|
|C S Mott Children's Hospital||Ann Arbor, Michigan 48109|
|Children's Healthcare of Atlanta - Egleston||Atlanta, Georgia 30322|
|Children's Hospital Colorado||Aurora, Colorado 80045|
|Children's Hospital-Main Campus||New Orleans, Louisiana 70118|