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Etanercept in Treating Young Patients With Idiopathic Pneumonia Syndrome After Undergoing a Donor Stem Cell Transplant
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), November 2009
First Received: March 29, 2006   Last Updated: November 19, 2009   History of Changes
Sponsor: Children's Oncology Group
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00309907
  Purpose

RATIONALE: Etanercept may be effective in treating patients with idiopathic pneumonia syndrome after undergoing a donor stem cell transplant.

PURPOSE: 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.


Condition Intervention Phase
Kidney Cancer
Leukemia
Lymphoma
Myelodysplastic Syndromes
Neuroblastoma
Pulmonary Complications
Sarcoma
Biological: etanercept
Drug: methylprednisolone
Phase II

Study Type: Interventional
Study Design: Supportive Care, Non-Randomized, Open Label
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response at 28 days [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Survival at 56 days [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Time to discontinuation of supplemental oxygen support [ Designated as safety issue: No ]
  • Toxicity as measured by CTC version 3.0 [ Designated as safety issue: Yes ]
  • Bronchoalveolar lavage fluid and serum cytokine pro-inflammatory markers as assessed by enzyme-linked immunosorbent assays [ Designated as safety issue: No ]
  • C-reactive protein levels at baseline and days 7, 14, 21, and 28 [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: April 2006
Estimated Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • 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

  • Estimate the day 56 survival rate in patients treated with this drug.
  • Determine the overall survival distribution in patients treated with this drug.
  • Determine the pulmonary response, as defined as the time to discontinuation of supplemental oxygen, in patients treated with this drug.
  • Evaluate the toxicity of etanercept therapy in patients with IPS.
  • Evaluate levels of pro-inflammatory cytokines, in both bronchoalveolar lavage (BAL) fluid and serum, in patients with IPS.
  • 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.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   1 Year to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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 < 5 mcg/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

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • 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
  • Concurrent treatment for acute or chronic GVHD allowed
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00309907

  Hide Study Locations
Locations
United States, Alabama
UAB Comprehensive Cancer Center Recruiting
Birmingham, Alabama, United States, 35294
Contact: Clinical Trials Office - UAB Comprehensive Cancer Center     205-934-0309        
United States, California
Children's Hospital and Research Center Oakland Recruiting
Oakland, California, United States, 94609
Contact: Clinical Trial Office - Children's Hospital and Research Cente     510-450-7600        
Childrens Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
Contact: Leo Mascarenhas     323-361-2529        
Loma Linda University Cancer Institute at Loma Linda University Medical Center Recruiting
Loma Linda, California, United States, 92354
Contact: Clinical Trials Office - Loma Linda University Cancer Institut     909-558-3375        
Stanford Cancer Center Recruiting
Stanford, California, United States, 94305-5824
Contact: Clinical Trials Office - Stanford Cancer Center     650-498-7061     cctoffice@stanford.edu    
United States, Colorado
Children's Hospital Center for Cancer and Blood Disorders Recruiting
Aurora, Colorado, United States, 80045
Contact: Kelly Maloney     720-777-6673        
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20010-2970
Contact: Clinical Trials Office - Children's National Medical Center     202-884-2549        
United States, Florida
All Children's Hospital Recruiting
St. Petersburg, Florida, United States, 33701
Contact: Gregory Hale     727-767-4176        
Nemours Children's Clinic Recruiting
Jacksonville, Florida, United States, 32207
Contact: Eric S. Sandler     904-697-3793        
United States, Georgia
Winship Cancer Institute of Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Howard M. Katzenstein     404-785-0853        
United States, Illinois
Children's Memorial Hospital - Chicago Recruiting
Chicago, Illinois, United States, 60614
Contact: Stewart Goldman     773-880-3270        
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202-5289
Contact: Clinical Trials Office - Indiana University Cancer Center     317-274-2552        
United States, Kentucky
Kosair Children's Hospital Recruiting
Louisville, Kentucky, United States, 40232
Contact: Clinical Trials Office - Kosair Children's Hospital     502-629-5500     CancerResource@nortonhealthcare.org    
United States, Louisiana
Children's Hospital of New Orleans Recruiting
New Orleans, Louisiana, United States, 70118
Contact: Clinical Trials Office - Children's Hospital of New Orleans     504-894-5377        
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21231-2410
Contact: Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Ce     410-955-8804     jhcccro@jhmi.edu    
United States, Massachusetts
Floating Hospital for Children at Tufts - New England Medical Center Recruiting
Boston, Massachusetts, United States, 02111
Contact: Cynthia S. Kretschmar     617-636-5535        
United States, Michigan
Butterworth Hospital at Spectrum Health Recruiting
Grand Rapids, Michigan, United States, 49503-2560
Contact: David S. Dickens     616-391-2086        
C.S. Mott Children's Hospital at University of Michigan Medical Center Recruiting
Ann Arbor, Michigan, United States, 48109-0286
Contact: Clinical Trials Office - C.S. Mott Children's Hospital     800-865-1125        
United States, Minnesota
Masonic Cancer Center at University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Clinical Trials Office - Masonic Cancer Center at University o     612-624-2620        
United States, Mississippi
University of Mississippi Cancer Clinic Recruiting
Jackson, Mississippi, United States, 39216-4505
Contact: Gail C. Megason     601-984-5220        
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis Recruiting
St. Louis, Missouri, United States, 63110
Contact: Robert J. Hayashi     314-454-4118        
United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198-6805
Contact: Clinical Trials Office - UNMC Eppley Cancer Center at the Univ     800-999-5465        
United States, New Jersey
Hackensack University Medical Center Cancer Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Clinical Trials Office - Hackensack University Medical Center     201-996-2879        
United States, New York
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Clinical Trials Office - Herbert Irving Comprehensive Cancer C     212-305-8615        
Mount Sinai Medical Center Recruiting
New York, New York, United States, 10029
Contact: Birte Wistinghausen     212-241-7022        
New York Medical College Recruiting
Valhalla, New York, United States, 10595
Contact: Fevzi Ozkaynak     914-493-7997        
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229-3039
Contact: Clinical Trials Office - Cincinnati Children's Hospital Medica     513-636-2799        
Rainbow Babies and Children's Hospital Recruiting
Cleveland, Ohio, United States, 44106-5000
Contact: Yousif (Joe) H. Matloub     216-844-3345        
United States, Oklahoma
Oklahoma University Cancer Institute Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Rene Y. McNall-Knapp     405-271-5311        
United States, Oregon
Knight Cancer Institute at Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239-3098
Contact: Clinical Trials Office - Knight Cancer Institute at Oregon Hea     503-494-1080     trials@ohsu.edu    
United States, Pennsylvania
Children's Hospital of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Clinical Trials Office - Children's Hospital of Pittsburgh     412-692-5573        
United States, Texas
Cook Children's Medical Center - Fort Worth Recruiting
Fort Worth, Texas, United States, 76104
Contact: Clinical Trials Office - Cook's Children's Medical Center     682-885-2103        
M. D. Anderson Cancer Center at University of Texas Recruiting
Houston, Texas, United States, 77030-4009
Contact: Clinical Trials Office - M. D. Anderson Cancer Center at the U     713-792-3245        
Methodist Children's Hospital of South Texas Recruiting
San Antonio, Texas, United States, 78229-3993
Contact: Michael S. Grimley     210-575-7268        
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas Recruiting
Dallas, Texas, United States, 75390
Contact: Clinical Trials Office - Simmons Comprehensive Cancer Center a     866-460-4673; 214-648-7097        
United States, Utah
Primary Children's Medical Center Recruiting
Salt Lake City, Utah, United States, 84113-1100
Contact: Phillip E. Barnette     801-662-4700        
United States, Virginia
Virginia Commonwealth University Massey Cancer Center Recruiting
Richmond, Virginia, United States, 23298-0037
Contact: Clinical Trials Office -Virginia Commonwealth University Masse     804-628-1939        
United States, Washington
Children's Hospital and Regional Medical Center - Seattle Recruiting
Seattle, Washington, United States, 98105
Contact: Julie R. Park     206-987-2106        
United States, Wisconsin
Midwest Children's Cancer Center at Children's Hospital of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Michael E. Kelly     414-456-4170        
Canada, British Columbia
Children's & Women's Hospital of British Columbia Recruiting
Vancouver, British Columbia, Canada, V6H 3V4
Contact: Mason C. Bond     604-875-2322        
Canada, Ontario
Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Sylvain Baruchel     416-813-7795        
Canada, Quebec
Hopital Sainte Justine Recruiting
Montreal, Quebec, Canada, H3T 1C5
Contact: Yvan Samson     418-656-4141x47191        
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Gregory Yanik, MD University of Michigan Cancer Center
Investigator: Kenneth R. Cooke, MD University of Michigan Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Oncology Group - Group Chair Office ( Gregory H. Reaman )
Study ID Numbers: CDR0000456407, COG-ASCT0521, COG-PBMTC-SUP051
Study First Received: March 29, 2006
Last Updated: November 19, 2009
ClinicalTrials.gov Identifier: NCT00309907     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
recurrent Wilms tumor and other childhood kidney tumors
childhood acute lymphoblastic leukemia in remission
childhood acute myeloid leukemia in remission
childhood chronic myelogenous leukemia
de novo myelodysplastic syndromes
disseminated neuroblastoma
juvenile myelomonocytic leukemia
previously treated childhood rhabdomyosarcoma
previously treated myelodysplastic syndromes
recurrent/refractory childhood Hodgkin lymphoma
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
relapsing chronic myelogenous leukemia
secondary acute myeloid leukemia
secondary myelodysplastic syndromes
pulmonary complications
childhood myelodysplastic syndromes

Additional relevant MeSH terms:
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Neoplasms by Site
Neoplasms, Connective and Soft Tissue
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors
Neoplasms, Nerve Tissue
Neoplasms by Histologic Type
Anti-Inflammatory Agents
Methylprednisolone
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
TNFR-Fc fusion protein
Hormones
Preleukemia
Pathologic Processes
Therapeutic Uses
Kidney Diseases
Methylprednisolone Hemisuccinate
Immunoproliferative Disorders
Antineoplastic Agents, Hormonal
Immune System Diseases
Hematologic Diseases

ClinicalTrials.gov processed this record on November 20, 2009