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

Phase 2
1 Year
17 Years
Not Enrolling
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

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Trial Information

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


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.


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.

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

- Room air oxygen saturation < 93%

- Supplemental oxygen required to maintain an oxygen saturation ≥

- Absence of active lower respiratory tract infection, defined as
Bronchoalveolar lavage (BAL)-negative for infection based on one of the

- 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 <

- 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

Type of Study:


Study Design:

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

Outcome Measure:

Number of patients with IPS who respond to etanercept and corticosteroid therapy plus complete discontinuation all supplemental oxygen support

Outcome Description:

The "time to response" will be defined as the first of 3 consecutive days in which all supplemental oxygen has been discontinued. Subjects who discontinue supplemental oxygen support during the study period (Day 0-28), but subsequently require re-institution of supplemental oxygen, will still be deemed as responders provided they meet the response criteria listed above. The median duration of time (number of days) that a patient requires supplemental oxygen will be determined using standard descriptive statistics, or Kaplan-Meier methods in the case of censoring.

Outcome Time Frame:

At day 28

Safety Issue:


Principal Investigator

Gregory Yanik

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group


United States: Institutional Review Board

Study ID:




Start Date:

April 2006

Completion Date:

Related Keywords:

  • 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
  • Blast Crisis
  • Hodgkin Disease
  • Kidney Neoplasms
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myeloid, Accelerated Phase
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Leukemia, Myeloid, Chronic-Phase
  • Lymphoma
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Myelodysplastic Syndromes
  • Preleukemia
  • Leukemia, Myelomonocytic, Acute
  • Leukemia, Myelomonocytic, Chronic
  • Wilms Tumor
  • Neuroblastoma
  • Pneumonia
  • Rhabdomyosarcoma
  • Rhabdomyosarcoma, Embryonal
  • Leukemia, Myelomonocytic, Juvenile



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