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Etanercept in Treating Young Patients With Idiopathic Pneumonia Syndrome After Undergoing a Donor Stem Cell Transplant

Information source: Children's Oncology Group
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Accelerated Phase Chronic Myelogenous Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Disseminated Neuroblastoma; Juvenile Myelomonocytic Leukemia; Previously Treated Childhood Rhabdomyosarcoma; Previously Treated Myelodysplastic Syndromes; Pulmonary Complications; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Neuroblastoma; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Recurrent/Refractory Childhood Hodgkin Lymphoma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

Intervention: etanercept (Biological); methylprednisolone (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Children's Oncology Group

Official(s) and/or principal investigator(s):
Gregory Yanik, MD, Principal Investigator, Affiliation: Children's Oncology Group

Summary

This phase II trial is studying how well etanercept works in treating young patients with idiopathic pneumonia syndrome after undergoing a donor stem cell transplant. Etanercept may be effective in treating patients with idiopathic pneumonia syndrome after undergoing a donor stem cell transplant.

Clinical Details

Official title: Soluble Tumor Necrosis Factor Receptor: Enbrel® (Etanercept) for the Treatment of Acute Non-Infectious Pulmonary Dysfunction (Idiopathic Pneumonia Syndrome) Following Allogeneic Stem Cell Transplantation

Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Response of IPS (Idiopathic Pneumonia Syndrome) to Etanercept Plus Corticosteroid Therapy by Day 28.

Secondary outcome:

Survival Rate

Time to Discontinuation of Supplemental Oxygen Support

Toxicity of Etanercept Plus Corticosteroid Therapy Using the Common Terminology Criteria Version 4.0

Levels of Pro-inflammatory Cytokines, in Both BAL (Bronchoalveolar Lavage) Fluid and Serum as Assessed by Enzyme-linked Immunosorbent Assays

C-reactive Protein Levels

Detailed description: PRIMARY OBJECTIVES: 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. SECONDARY OBJECTIVES: 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.

Eligibility

Minimum age: 1 Year. Maximum age: 17 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Diagnosis of acute, noninfectious idiopathic pulmonary dysfunction (IPS) as defined

by the following:

- Evidence of diffuse lung injury occurring within the first several months after

hematopoietic stem cell transplantation for which an infectious etiology is not identified. To meet the criteria for IPS there must be:

- Evidence of widespread alveolar injury

- Diffuse multi-lobar infiltrates on chest x-ray or CT scan

- Evidence for abnormal respiratory physiology based upon 1 of the

following:

- Room air oxygen saturation < 93%

- Supplemental oxygen required to maintain an oxygen saturation ≥

93%

- Absence of active lower respiratory tract infection, defined as

Bronchoalveolar lavage (BAL)-negative for infection based on one of the following:

- Gram stain, fungal stain, acid-fast bacilli stain

- Bacterial culture (a quantitative culture ≥ 10^4 colony-forming

units/mL is considered positive)

- Fungal culture

- Mycobacterial culture

- Viral culture (respiratory syncytial virus [RSV], parainfluenza,

adenovirus, influenza A and B, and cytomegalovirus [CMV])

- If direct fluorescent antibody (DFA) screening is performed on

BAL, it must be negative for all viruses listed above

- Pneumocystis carinii pneumonia by polymerase chain reaction (PCR), DFA

stain, or cytology

- Evidence of bilateral pulmonary infiltrates (on chest radiograph)

- Patients may have diffuse alveolar hemorrhage (DAH) or peri-engraftment

respiratory distress syndrome (PERDS)

- Presence of "mixed oral flora," "rare Candida species," or the presence of a

Penicillium species reported on BAL fluid analysis allowed

- A radiographic finding of pulmonary edema does not exclude the diagnosis of IPS,

provided the other criteria have been met and provided the treating physician concludes by clinical (or echocardiographic) criteria that the pulmonary edema is not secondary to cardiac dysfunction or iatrogenic fluid overload

- Patients must require supplemental oxygen

- Must have undergone an allogeneic bone marrow, cord blood, or peripheral blood stem

cell transplantation within the past 120 days

- There are no restrictions based upon underlying disease, donor source, the

degree of HLA match, the intensity of the pre-transplant conditioning regimen, or the use of a prior donor leukocyte infusion

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No documented invasive fungal or systemic viral infection within the past 14 days

- Patients with asymptomatic viruria allowed

- No signs of CMV reactivation (by CMV, PCR, antigenemia, or shell vial culture) within

the past 14 days

- No sepsis syndrome or hypotension that requires inotropic support (except dopamine <

5mcg/kg/minute)

- No documented bacteremia within the past 48 hours

- Persistent fever allowed

- No evidence of cardiac failure by clinical or echocardiographic findings

- No known hypersensitivity to etanercept

- No known history of tuberculosis (Tb) or prior Tb exposure

- No prior chronic hepatitis B or hepatitis C infection

- Concurrent treatment for acute or chronic GVHD allowed

- More than 14 days since prior etanercept

- More than 7 days since prior investigational drug trials (phase I, II, or III) for

the treatment of acute graft-versus-host disease (GVHD)

- Not on mechanical ventilation for > 48 continuous hours prior to study entry

- Must not be receiving > 2 mg/kg/day of methylprednisolone or corticosteroid

equivalent within 24 hours of study entry

- Concurrent continuous veno-venous hemofiltration or hemodialysis allowed

Locations and Contacts

University of Alabama at Birmingham, Birmingham, Alabama 35294, United States

Children's Oncology Group, Arcadia, California 91006-3776, United States

Loma Linda University Medical Center, Loma Linda, California 92354, United States

Children's Hospital Colorado, Aurora, Colorado 80045, United States

Children's National Medical Center, Washington, District of Columbia 20010, United States

All Children's Hospital, Saint Petersburg, Florida 33701, United States

Children's Healthcare of Atlanta - Egleston, Atlanta, Georgia 30322, United States

Childrens Memorial Hospital, Chicago, Illinois 60614, United States

Indiana University Cancer Center, Indianapolis, Indiana 46202, United States

Indiana University Medical Center, Indianapolis, Indiana 46202, United States

Children's Hospital-Main Campus, New Orleans, Louisiana 70118, United States

Johns Hopkins University, Baltimore, Maryland 21287-8936, United States

C S Mott Children's Hospital, Ann Arbor, Michigan 48109, United States

University of Nebraska Medical Center, Omaha, Nebraska 68198, United States

Hackensack University Medical Center, Hackensack, New Jersey 07601, United States

Columbia University Medical Center, New York, New York 10032, United States

New York Medical College, Valhalla, New York 10595, United States

Oregon Health and Science University, Portland, Oregon 97239, United States

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States

Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania 15224, United States

Medical University of South Carolina, Charleston, South Carolina 29425, United States

University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States

Cook Children's Medical Center, Fort Worth, Texas 76104, United States

Methodist Children's Hospital of South Texas, San Antonio, Texas 78229, United States

Seattle Children's Hospital, Seattle, Washington 98105, United States

Midwest Children's Cancer Center, Milwaukee, Wisconsin 53226, United States

Additional Information

Starting date: April 2006
Last updated: February 23, 2015

Page last updated: August 20, 2015

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