Trial Outcomes & Findings for Etanercept in Treating Young Patients With Idiopathic Pneumonia Syndrome After Undergoing a Donor Stem Cell Transplant (NCT NCT00309907)

Last Updated: 2017-09-29

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

39 participants

Primary outcome timeframe

At day 28

Results posted on

2017-09-29

Participant Flow

Participant milestones

Participant milestones
Measure	Etanercept and Corticosteroid Therapy 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. etanercept: Given IV and subcutaneously methylprednisolone: Given IV and orally
Overall Study STARTED	39
Overall Study COMPLETED	19
Overall Study NOT COMPLETED	20

Reasons for withdrawal

Reasons for withdrawal
Measure	Etanercept and Corticosteroid Therapy 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. etanercept: Given IV and subcutaneously methylprednisolone: Given IV and orally
Overall Study Death	4
Overall Study Physician Decision	1
Overall Study Ineligible	11
Overall Study Major infectious event	4

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Etanercept and Corticosteroid Therapy n=39 Participants 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. etanercept: Given IV and subcutaneously methylprednisolone: Given IV and orally
Age, Continuous	11 years n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants
Race (NIH/OMB) White	22 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	33 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	35 participants n=5 Participants
Region of Enrollment Canada	2 participants n=5 Participants
Region of Enrollment Sri Lanka	1 participants n=5 Participants
Region of Enrollment Saudi Arabia	1 participants n=5 Participants

PRIMARY outcome

Timeframe: At day 28

Population: Analysis population includes all patients who are eligible and had sufficient data to evaluate response. Eleven ineligible patients are excluded.

Outcome measures

Outcome measures
Measure	Etanercept and Corticosteroid Therapy n=28 Participants 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. etanercept: Given IV and subcutaneously methylprednisolone: Given IV and orally
Response of IPS (Idiopathic Pneumonia Syndrome) to Etanercept Plus Corticosteroid Therapy by Day 28. With Response	20 participants
Response of IPS (Idiopathic Pneumonia Syndrome) to Etanercept Plus Corticosteroid Therapy by Day 28. Without Response	8 participants

SECONDARY outcome

Timeframe: Up to day 56

Population: Analysis population includes all patients who are eligible and had sufficient data to evaluate response. Eleven ineligible patients are excluded.

Estimated Day 56 survival rate following initiation of etanercept + corticosteroid therapy for patients with IPS.

Outcome measures

Outcome measures
Measure	Etanercept and Corticosteroid Therapy n=28 Participants 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. etanercept: Given IV and subcutaneously methylprednisolone: Given IV and orally
Survival Rate	75 percentage of participants Interval 55.0 to 87.0

SECONDARY outcome

Timeframe: up to day 56

Population: Total of 28 patients are evaluable for this outcome.

Pulmonary response is defined as alive \& come off of oxygen .

Outcome measures

Outcome measures
Measure	Etanercept and Corticosteroid Therapy n=28 Participants 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. etanercept: Given IV and subcutaneously methylprednisolone: Given IV and orally
Estimate Percentage Pulmonary Response in Patients With IPS Treated With Etanercept + Corticosteroid Therapy	74 percentage of participants

SECONDARY outcome

Timeframe: Up to 56 days

Population: 28 patients evaluable for this outcome.

Grade 3-5 organ toxicities attributable to etanercept.

Outcome measures

Outcome measures
Measure	Etanercept and Corticosteroid Therapy n=28 Participants 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. etanercept: Given IV and subcutaneously methylprednisolone: Given IV and orally
Toxicity of Etanercept Plus Corticosteroid Therapy Using the Common Terminology Criteria Version 4.0	0 Patients

SECONDARY outcome

Timeframe: From baseline to days 7 and 28

Population: Plasma samples were available for biomarker analysis in 26 patients. The data were intended to be analyzed for all subjects, therefore, combined result is reported.

Estimated mean and standard error of IL6 level

Outcome measures

Outcome measures
Measure	Etanercept and Corticosteroid Therapy n=26 Participants 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. etanercept: Given IV and subcutaneously methylprednisolone: Given IV and orally
Plasma Cytokine IL6 Level Baseline	205.2 pg/ml Standard Error 58
Plasma Cytokine IL6 Level Day 7	28.8 pg/ml Standard Error 4.4
Plasma Cytokine IL6 Level Day 28	23.1 pg/ml Standard Error 3.5

SECONDARY outcome

Timeframe: From baseline to days 7, 14, 21, and 28

Population: The data for baseline were intended to be analyzed for all subjects, therefore, combined result is reported. The data for Days 7, 14, 21 and 28 were intended to be analyzed by subgroups of subjects as pre-specified in the study protocol, therefore combined result us not reported for Etanercept + corticosteroid therapy treatment arm.

Estimated mean and standard deviation

Outcome measures

Outcome measures
Measure	Etanercept and Corticosteroid Therapy n=28 Participants 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. etanercept: Given IV and subcutaneously methylprednisolone: Given IV and orally
C-reactive Protein Levels Baseline	28.1 mg/dL Standard Deviation 59.1
C-reactive Protein Levels Day 7 Non Responders	5.4 mg/dL Standard Deviation 11.4
C-reactive Protein Levels Day 7 Responders	1.8 mg/dL Standard Deviation 1.9
C-reactive Protein Levels Day 14 Non Responders	4.9 mg/dL Standard Deviation 11.1
C-reactive Protein Levels Day 14 Responders	1 mg/dL Standard Deviation 1.1
C-reactive Protein Levels Day 21 Non Responders	10.7 mg/dL Standard Deviation 14.3
C-reactive Protein Levels Day 21 Responders	1.6 mg/dL Standard Deviation 2.4
C-reactive Protein Levels Day 28 Non Responders	19.6 mg/dL Standard Deviation 29.7
C-reactive Protein Levels Day 28 Responders	5.3 mg/dL Standard Deviation 16.1

Adverse Events

Etanercept and Corticosteroid Therapy

Serious events: 5 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Etanercept and Corticosteroid Therapy n=28 participants at risk 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. etanercept: Given IV and subcutaneously methylprednisolone: Given IV and orally
Renal and urinary disorders Acute kidney injury	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
Respiratory, thoracic and mediastinal disorders Adult respiratory distress syndrome	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
Metabolism and nutrition disorders Alkalosis	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
Investigations Blood bilirubin increased	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
General disorders Death NOS	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
Gastrointestinal disorders Esophageal hemorrhage	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
Metabolism and nutrition disorders Hyperglycemia	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
Respiratory, thoracic and mediastinal disorders Hypoxia	7.1% 2/28 Eleven ineligible patients are not reported in the adverse events.
Infections and infestations Infections and infestations - Other, specify	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
General disorders Multi-organ failure	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
Nervous system disorders Nervous system disorders - Other, specify	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
Nervous system disorders Peripheral motor neuropathy	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
Respiratory, thoracic and mediastinal disorders Pleural effusion	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
Respiratory, thoracic and mediastinal disorders Pneumonitis	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
Respiratory, thoracic and mediastinal disorders Pneumothorax	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
Infections and infestations Upper respiratory infection	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
Cardiac disorders Ventricular arrhythmia	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.

Other adverse events

Other adverse events
Measure	Etanercept and Corticosteroid Therapy n=28 participants at risk 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. etanercept: Given IV and subcutaneously methylprednisolone: Given IV and orally
Renal and urinary disorders Acute kidney injury	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
Gastrointestinal disorders Ascites	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
Investigations Creatinine increased	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
Infections and infestations Enterocolitis infectious	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
Hepatobiliary disorders Hepatic failure	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
Metabolism and nutrition disorders Hyperglycemia	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
Metabolism and nutrition disorders Hypokalemia	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
Infections and infestations Infections and infestations - Other, specify	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
Investigations Neutrophil count decreased	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
Investigations Platelet count decreased	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
Respiratory, thoracic and mediastinal disorders Pneumothorax	3.6% 1/28 Eleven ineligible patients are not reported in the adverse events.
Investigations White blood cell decreased	7.1% 2/28 Eleven ineligible patients are not reported in the adverse events.

Additional Information

Results Reporting Coordinator

Children's Oncology Group

Phone: 352-273-0567

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place