Clinical trial NCT00309907: Etanercept in Treating Young Patients With Idiopathic Pneumonia Syndrome After Undergoing a Donor Stem Cell Transplant
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-04-03
Enrollment: 39
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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 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

Primary outcomes:
measure: Response of IPS (Idiopathic Pneumonia Syndrome) to Etanercept Plus Corticosteroid Therapy by Day 28.
timeFrame: At day 28
Secondary outcomes:
measure: Survival Rate
timeFrame: Up to day 56
measure: Estimate Percentage Pulmonary Response in Patients With IPS Treated With Etanercept + Corticosteroid Therapy
timeFrame: up to day 56
measure: Toxicity of Etanercept Plus Corticosteroid Therapy Using the Common Terminology Criteria Version 4.0
timeFrame: Up to 56 days
measure: Plasma Cytokine IL6 Level
timeFrame: From baseline to days 7 and 28
measure: C-reactive Protein Levels
timeFrame: From baseline to days 7, 14, 21, and 28
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Arcadia
country: United States
facility: Children's Oncology Group
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Washington, D.C.
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Saint Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta - Egleston
state: Georgia
city: Chicago
country: United States
facility: Childrens Memorial Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Medical Center
state: Indiana
city: New Orleans
country: United States
facility: Children's Hospital-Main Campus
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Ann Arbor
country: United States
facility: C S Mott Children's Hospital
state: Michigan
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: San Antonio
country: United States
facility: Methodist Children's Hospital of South Texas
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Milwaukee
country: United States
facility: Midwest Children's Cancer Center
state: Wisconsin
Study officials:
affiliation: Children's Oncology Group
name: Gregory Yanik, MD
role: PRINCIPAL_INVESTIGATOR
References: