Etanercept in Treating Young Patients With Idiopathic Pneumonia Syndrome After Undergoing a Donor Stem Cell Transplant
Accelerated Phase Chronic Myelogenous Leukemia, Blastic Phase Chronic Myelogenous Leukemia, Childhood Acute Lymphoblastic Leukemia in Remission
About this trial
This is an interventional treatment trial for Accelerated Phase Chronic Myelogenous Leukemia
Eligibility 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
Sites / Locations
- University of Alabama at Birmingham
- Children's Oncology Group
- Loma Linda University Medical Center
- Children's Hospital Colorado
- Children's National Medical Center
- All Children's Hospital
- Children's Healthcare of Atlanta - Egleston
- Childrens Memorial Hospital
- Indiana University Cancer Center
- Indiana University Medical Center
- Children's Hospital-Main Campus
- Johns Hopkins University
- C S Mott Children's Hospital
- University of Nebraska Medical Center
- Hackensack University Medical Center
- Columbia University Medical Center
- New York Medical College
- Oregon Health and Science University
- Children's Hospital of Philadelphia
- Children's Hospital of Pittsburgh of UPMC
- Medical University of South Carolina
- University of Texas Southwestern Medical Center
- Cook Children's Medical Center
- Methodist Children's Hospital of South Texas
- Seattle Children's Hospital
- Midwest Children's Cancer Center
Arms of the Study
Arm 1
Experimental
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.