Accelerated Phase Chronic Myelogenous LeukemiaPhase 2NCT00309907
Etanercept in Treating Young Patients With Idiopathic Pneumonia Syndrome After Undergoing a Donor Stem Cell Transplant
A Phase 2 study testing etanercept and methylprednisolone in people with Accelerated Phase Chronic Myelogenous Leukemia and Blastic Phase Chronic Myelogenous Leukemia, run by Children's Oncology Group at 26 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 17 years
- Conditions the study is for
- Accelerated Phase Chronic Myelogenous Leukemia, Blastic Phase Chronic Myelogenous Leukemia, Childhood Acute Lymphoblastic Leukemia in Remission
- What is being tested?
- etanercept and methylprednisolone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 26 sitesUnited States
- Study dates
- Apr 2006to Sep 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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%
Show all 41Show fewer
- 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
Who cannot join
None listed.
Trial locations and contacts
26 sites in 1 country.
26 sites in 1 country
United States26 sites
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
Children's Oncology Group
Arcadia, California, 91006-3776
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322
Children's Hospital Colorado
Aurora, Colorado, 80045
Johns Hopkins University
Baltimore, Maryland, 21287-8936
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Medical University of South Carolina
Charleston, South Carolina, 29425
Childrens Memorial Hospital
Chicago, Illinois, 60614
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Cook Children's Medical Center
Fort Worth, Texas, 76104
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Indiana University Cancer Center
Indianapolis, Indiana, 46202
Indiana University Medical Center
Indianapolis, Indiana, 46202
Loma Linda University Medical Center
Loma Linda, California, 92354
Midwest Children's Cancer Center
Milwaukee, Wisconsin, 53226
Children's Hospital-Main Campus
New Orleans, Louisiana, 70118
Columbia University Medical Center
New York, New York, 10032
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Oregon Health and Science University
Portland, Oregon, 97239
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229
Seattle Children's Hospital
Seattle, Washington, 98105
All Children's Hospital
St. Petersburg, Florida, 33701
New York Medical College
Valhalla, New York, 10595
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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
- Being tested
- etanercept, methylprednisolone
- Medical subject headings
- Leukemia, Myeloid, Accelerated Phase, Blast Crisis, Leukemia, Myeloid, Chronic-Phase, Leukemia, Myelomonocytic, Juvenile, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Dendritic Cell Sarcoma, Interdigitating, Burkitt Lymphoma, Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
etanerceptBiological
Also called Enbrel, ETN, TNFR:Fc, Tumor Necrosis Factor Receptor IgG Chimera
Given IV and subcutaneously
Also called Depo-Medrol, Medrol, MePRDL, Solu-Medrol
Given IV and orally
| Study group | Role | What they receive |
|---|---|---|
| Etanercept and corticosteroid therapy | Experimental | 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. Receives: Biological: etanercept; Drug: methylprednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At day 28
Secondary outcomes (5)
Survival Rate
Estimated Day 56 survival rate following initiation of etanercept + corticosteroid therapy for patients with IPS.
Measured: Up to day 56
Estimate Percentage Pulmonary Response in Patients With IPS Treated With Etanercept + Corticosteroid Therapy
Pulmonary response is defined as alive \& come off of oxygen .
Measured: up to day 56
Toxicity of Etanercept Plus Corticosteroid Therapy Using the Common Terminology Criteria Version 4.0
Grade 3-5 organ toxicities attributable to etanercept.
Measured: Up to 56 days
Plasma Cytokine IL6 Level
Estimated mean and standard error of IL6 level
Measured: From baseline to days 7 and 28
C-reactive Protein Levels
Estimated mean and standard deviation
Measured: From baseline to days 7, 14, 21, and 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2006 (estimated)
- Study startApr 2006
- Primary completionSep 2011
- Study completionSep 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Accelerated Phase Chronic Myelogenous LeukemiaStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Gregory Yanik, MD, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00309907
- Sponsor's protocol ID
- ASCT0521
- Other IDs
- NCI-2009-00429, COG-PBMTC-SUP051, COG-ASCT0521, CDR0000456407, U10CA098543
- Status last verified
- Feb 2017
- First submitted
- 29 Mar 2006
- Last updated
- 29 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00309907
- Acronym / sponsor ID
- ASCT0521
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Apr 2006
- Primary completion
- Sep 2011 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 3 Apr 2006 (estimated)
- Results
- Posted 14 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Etanercept and corticosteroid therapy | Experimental | Biological: etanercept, Drug: methylprednisolonePatients 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. |
Who may qualify
- Ages
- 1 year to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (41 listed)
- Diagnosis of acute, noninfectious idiopathic pulmonary dysfunction (IPS) as defined by the following:
- 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
- Not pregnant or nursing
- Negative pregnancy test
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| etanerceptAlso: Enbrel, ETN, TNFR:Fc, Tumor Necrosis Factor Receptor IgG ChimeraGiven IV and subcutaneously | Biological | Etanercept and corticosteroid therapy |
| methylprednisoloneAlso: Depo-Medrol, Medrol, MePRDL, Solu-MedrolGiven IV and orally | Drug | Etanercept and corticosteroid therapy |
Primary outcome
Response of IPS (Idiopathic Pneumonia Syndrome) to Etanercept Plus Corticosteroid Therapy by Day 28.
Time frame: At 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.
5 secondary outcomes
Survival Rate
Time frame: Up to day 56
Estimate Percentage Pulmonary Response in Patients With IPS Treated With Etanercept + Corticosteroid Therapy
Time frame: up to day 56
Toxicity of Etanercept Plus Corticosteroid Therapy Using the Common Terminology Criteria Version 4.0
Time frame: Up to 56 days
Plasma Cytokine IL6 Level
Time frame: From baseline to days 7 and 28
C-reactive Protein Levels
Time frame: From baseline to days 7, 14, 21, and 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gregory Yanik, MD principal investigator
Children's Oncology Group
26 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing etanercept and methylprednisolone in people with Accelerated Phase Chronic Myelogenous Leukemia and Blastic Phase Chronic Myelogenous Leukemia, run by Children's Oncology Group at 26 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 41 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response of IPS (Idiopathic Pneumonia Syndrome) to Etanercept Plus Corticosteroid Therapy by Day 28. (time frame: At day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2017.