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

Secondary Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00309907
• Other study ID #: ASCT0521
• Secondary ID: NCI-2009-00429CO
• Status: Completed
• Phase: Phase 2
• First received: March 29, 2006
• Last updated: September 1, 2017
• Start date: April 2006
• Est. completion date: September 2011

Study information

• Verified date: February 2017
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: September 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 17 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Biological:
• etanercept
Given IV and subcutaneously

Drug:
• methylprednisolone
Given IV and orally

Locations

Country	Name	City	State
United States	C S Mott Children's Hospital	Ann Arbor	Michigan
United States	Children's Oncology Group	Arcadia	California
United States	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Childrens Memorial Hospital	Chicago	Illinois
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Indiana University Medical Center	Indianapolis	Indiana
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	Children's Hospital-Main Campus	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	All Children's Hospital	Saint Petersburg	Florida
United States	Methodist Children's Hospital of South Texas	San Antonio	Texas
United States	Seattle Children's Hospital	Seattle	Washington
United States	New York Medical College	Valhalla	New York
United States	Children's National Medical Center	Washington, D.C.	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	At day 28
Secondary	Survival Rate	Estimated Day 56 survival rate following initiation of etanercept + corticosteroid therapy for patients with IPS.	Up to day 56
Secondary	Estimate Percentage Pulmonary Response in Patients With IPS Treated With Etanercept + Corticosteroid Therapy	Pulmonary response is defined as alive & come off of oxygen .	up to day 56
Secondary	Toxicity of Etanercept Plus Corticosteroid Therapy Using the Common Terminology Criteria Version 4.0	Grade 3-5 organ toxicities attributable to etanercept.	Up to 56 days
Secondary	Plasma Cytokine IL6 Level	Estimated mean and standard error of IL6 level	From baseline to days 7 and 28
Secondary	C-reactive Protein Levels	Estimated mean and standard deviation	From baseline to days 7, 14, 21, and 28