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

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

39 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-04-30

Study Completion Date

2011-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Etanercept and corticosteroid therapy

Patients receive etanercept IV (dose 0.4 mg/kg- max 25 mg) over 30 minutes on day 0 and subcutaneously (dose 0.4 mg/kg- max 25 mg) 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 (dose 2.0 mg/kg/day) on days 0-2 and then orally with a taper beginning day 7. Dose on days 7-20 (1.0 mg/kg/day), days 21-34 (0.5 mg/kg/day), days 35-48 (0.25 mg/kg/day) and days 49-56 (0.25 mg/kg/every other day) discontinuing on day 56.

Group Type EXPERIMENTAL

etanercept

Intervention Type BIOLOGICAL

Given IV and subcutaneously

methylprednisolone

Intervention Type DRUG

Given IV and orally

Interventions

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etanercept

Given IV and subcutaneously

Intervention Type BIOLOGICAL

methylprednisolone

Given IV and orally

Intervention Type DRUG

Other Intervention Names

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Enbrel ETN TNFR:Fc Tumor Necrosis Factor Receptor IgG Chimera Depo-Medrol Medrol MePRDL Solu-Medrol Wyacort

Eligibility Criteria

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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

Minimum Eligible Age

1 Year

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gregory Yanik, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Children's Oncology Group

Arcadia, California, United States

Site Status

Loma Linda University Medical Center

Loma Linda, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

All Children's Hospital

St. Petersburg, Florida, United States

Site Status

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, United States

Site Status

Childrens Memorial Hospital

Chicago, Illinois, United States

Site Status

Indiana University Cancer Center

Indianapolis, Indiana, United States

Site Status

Indiana University Medical Center

Indianapolis, Indiana, United States

Site Status

Children's Hospital-Main Campus

New Orleans, Louisiana, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

New York Medical College

Valhalla, New York, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Cook Children's Medical Center

Fort Worth, Texas, United States

Site Status

Methodist Children's Hospital of South Texas

San Antonio, Texas, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Midwest Children's Cancer Center

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States