Etanercept in Treating Young Patients With Idiopathic Pneumonia Syndrome After Undergoing a Donor Stem Cell Transplant
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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 |
- Number of patients with IPS who respond to etanercept and corticosteroid therapy plus complete discontinuation all supplemental oxygen support [ Time Frame: At day 28 ] [ Designated as safety issue: No ]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.
- 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 ]
- Overall survival distribution [ Time Frame: Up to 56 days ] [ Designated as safety issue: No ]Overall survival will be estimated using Kaplan-Meier methods.
- Time to discontinuation of supplemental oxygen support [ Time Frame: Time from study to time on room air, assessed up to 28 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 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 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: | August 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment (immunomodulating therapy, corticosteroid therapy)
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.
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Biological: etanercept
Given IV and subcutaneously
Other Names:
Drug: methylprednisolone
Given IV and orally
Other Names:
|
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 |
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
Show 26 Study Locations| Principal Investigator: | Gregory Yanik | 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 |
| Last Updated: | June 14, 2013 |
| Health Authority: | United States: Institutional Review Board |
Additional relevant MeSH terms:
|
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 Neoplasms by Histologic Type Neoplasms Cell Transformation, Neoplastic Neoplastic Processes Myeloproliferative Disorders Bone Marrow Diseases |
ClinicalTrials.gov processed this record on June 17, 2013