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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00309907
First received: March 29, 2006
Last updated: February 14, 2014
Last verified: February 2014
  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. Etanercept may be effective in treating patients with idiopathic pneumonia syndrome after undergoing a donor stem cell transplant.


Condition Intervention Phase
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
Biological: etanercept
Drug: methylprednisolone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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 Children's Oncology Group:

Primary Outcome Measures:
  • Response of IPS (Idiopathic Pneumonia Syndrome) to Etanercept Plus Corticosteroid Therapy by Day 28. [ Time Frame: At day 28 ] [ Designated as safety issue: No ]
    Response to therapy is defined as survival to Day 28 of study, PLUS complete discontinuation all supplemental oxygen support by Day 28 of study. Subjects must be able to remain off all supplemental oxygen support for > 72 consecutive hours. Subjects who discontinue supplemental oxygen within the last 72 hours of the observation period will be followed until they have completed 72 consecutive hours off oxygen or failed prior to assessing response.


Secondary Outcome Measures:
  • Survival Rate [ Time Frame: From the first dose of treatment with etanercept to the date of last follow up or date of death, assessed up to 56 days ] [ Designated as safety issue: No ]
  • Time to Discontinuation of Supplemental Oxygen Support [ Time Frame: Time from study to time on room air, assessed up to 56 days ] [ Designated as safety issue: No ]
    The "time required to discontinue supplemental oxygen" will be measured in the number of days from study entry till the patient is on room air and will be estimated using the cumulative incidence estimator due to the competing risk of death.

  • Toxicity of Etanercept Plus Corticosteroid Therapy Using the Common Terminology Criteria Version 4.0 [ Time Frame: Up to 56 days ] [ Designated as safety issue: Yes ]
  • Levels of Pro-inflammatory Cytokines, in Both BAL (Bronchoalveolar Lavage) Fluid and Serum as Assessed by Enzyme-linked Immunosorbent Assays [ Time Frame: From baseline to days 7 and 56 ] [ Designated as safety issue: No ]
    Measurements will be summarized with means and standard deviations for subgroups of subjects (e.g. responders versus non-responders). Two-group comparisons of cytokines (e.g. responders versus non-responders) will likely be underpowered, and such comparisons will be done only to generate hypotheses for future studies. Comparative plasma cytokine assays will be performed in a similar fashion as that of the BAL fluid.

  • C-reactive Protein Levels [ Time Frame: From baseline to days 7, 14, 21, and 28 ] [ Designated as safety issue: No ]
    Measurements will be summarized with mean and standard deviations for subgroups of subjects (those who respond versus non-responders). Two group comparisons of CRP (C-reactive protein) levels (responders versus non-responders) will likely be underpowered, and such comparisons will be done to generate hypotheses for future studies.


Enrollment: 39
Study Start Date: April 2006
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: etanercept
Given IV and subcutaneously
Other Names:
  • Enbrel
  • ETN
  • TNFR:Fc
  • Tumor Necrosis Factor Receptor IgG Chimera
Drug: methylprednisolone
Given IV and orally
Other Names:
  • Depo-Medrol
  • Medrol
  • MePRDL
  • Solu-Medrol
  • Wyacort

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

Ages Eligible for Study:   1 Year to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00309907

  Show 26 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Gregory Yanik, MD Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00309907     History of Changes
Other Study ID Numbers: ASCT0521, NCI-2009-00429, COG-PBMTC-SUP051, COG-ASCT0521, CDR0000456407, U10CA098543
Study First Received: March 29, 2006
Results First Received: January 6, 2014
Last Updated: February 14, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasm Metastasis
Lymphoma
Leukemia
Syndrome
Hodgkin Disease
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neuroblastoma
Lymphoma, Non-Hodgkin
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Rhabdomyosarcoma
Leukemia, Myeloid, Chronic-Phase
Blast Crisis
Leukemia, Myeloid, Accelerated Phase
Rhabdomyosarcoma, Embryonal
Wilms Tumor
Leukemia, Myelomonocytic, Juvenile
Kidney Neoplasms
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Lymphoproliferative Disorders

ClinicalTrials.gov processed this record on September 18, 2014