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

Primary Purpose

Accelerated Phase Chronic Myelogenous Leukemia, Blastic Phase Chronic Myelogenous Leukemia, Childhood Acute Lymphoblastic Leukemia in Remission

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
etanercept
methylprednisolone
Sponsored by
Children's Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Accelerated Phase Chronic Myelogenous Leukemia

Eligibility Criteria

1 Year - 17 Years (Child)All SexesDoes not accept healthy volunteers

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

Arm Type

Experimental

Arm Label

Etanercept and corticosteroid therapy

Arm Description

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.

Outcomes

Primary Outcome Measures

Response of IPS (Idiopathic Pneumonia Syndrome) to Etanercept Plus Corticosteroid Therapy by Day 28.
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
Estimated Day 56 survival rate following initiation of etanercept + corticosteroid therapy for patients with IPS.
Estimate Percentage Pulmonary Response in Patients With IPS Treated With Etanercept + Corticosteroid Therapy
Pulmonary response is defined as alive & come off of oxygen .
Toxicity of Etanercept Plus Corticosteroid Therapy Using the Common Terminology Criteria Version 4.0
Grade 3-5 organ toxicities attributable to etanercept.
Plasma Cytokine IL6 Level
Estimated mean and standard error of IL6 level
C-reactive Protein Levels
Estimated mean and standard deviation

Full Information

First Posted
March 29, 2006
Last Updated
September 1, 2017
Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00309907
Brief Title
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

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
April 2006 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
September 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
39 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Etanercept and corticosteroid therapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
etanercept
Other Intervention Name(s)
Enbrel, ETN, TNFR:Fc, Tumor Necrosis Factor Receptor IgG Chimera
Intervention Description
Given IV and subcutaneously
Intervention Type
Drug
Intervention Name(s)
methylprednisolone
Other Intervention Name(s)
Depo-Medrol, Medrol, MePRDL, Solu-Medrol, Wyacort
Intervention Description
Given IV and orally
Primary Outcome Measure Information:
Title
Response of IPS (Idiopathic Pneumonia Syndrome) to Etanercept Plus Corticosteroid Therapy by Day 28.
Description
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.
Time Frame
At day 28
Secondary Outcome Measure Information:
Title
Survival Rate
Description
Estimated Day 56 survival rate following initiation of etanercept + corticosteroid therapy for patients with IPS.
Time Frame
Up to day 56
Title
Estimate Percentage Pulmonary Response in Patients With IPS Treated With Etanercept + Corticosteroid Therapy
Description
Pulmonary response is defined as alive & come off of oxygen .
Time Frame
up to day 56
Title
Toxicity of Etanercept Plus Corticosteroid Therapy Using the Common Terminology Criteria Version 4.0
Description
Grade 3-5 organ toxicities attributable to etanercept.
Time Frame
Up to 56 days
Title
Plasma Cytokine IL6 Level
Description
Estimated mean and standard error of IL6 level
Time Frame
From baseline to days 7 and 28
Title
C-reactive Protein Levels
Description
Estimated mean and standard deviation
Time Frame
From baseline to days 7, 14, 21, and 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gregory Yanik, MD
Organizational Affiliation
Children's Oncology Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Children's Oncology Group
City
Arcadia
State/Province
California
ZIP/Postal Code
91006-3776
Country
United States
Facility Name
Loma Linda University Medical Center
City
Loma Linda
State/Province
California
ZIP/Postal Code
92354
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Children's National Medical Center
City
Washington, D.C.
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
All Children's Hospital
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33701
Country
United States
Facility Name
Children's Healthcare of Atlanta - Egleston
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Childrens Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60614
Country
United States
Facility Name
Indiana University Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Indiana University Medical Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Children's Hospital-Main Campus
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70118
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287-8936
Country
United States
Facility Name
C S Mott Children's Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
New York Medical College
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Children's Hospital of Pittsburgh of UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Cook Children's Medical Center
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Methodist Children's Hospital of South Texas
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Midwest Children's Cancer Center
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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