CALIPSO: Calfactant for Acute Lung Injury in Pediatric Stem Cell Transplant and Oncology Patients

Study Overview
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Brief Summary
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Acute lung injury (ALI) is a common, life-threatening complication among pediatric leukemia and lymphoma and hematopoietic stem cell transplant (HSCT) recipients. Although these children represent a relatively small and unique patient population, they account for the largest proportion of deaths of all pediatric diseases. The long-term goal of this project is to improve outcomes among these patients. Recently, the intratracheal administration of calfactant has resulted in decreased mortality among children with ALI including promising results among children with cancer and following HSCT. Consequently, the primary specific aim of this study is to assess the effect of calfactant on intensive care (PICU) survival among pediatric leukemia and lymphoma and HSCT patients with ALI. Secondary aims include assessment of the effect of calfactant on oxygenation and on the length of mechanical ventilation, PICU stay, and hospital stay. Calfactant therapy has been found to be of benefit in acute lung injury in the overall pediatric population by improving oxygenation and decreasing mortality. These findings, in conjunction with recent subgroup analysis in which calfactant therapy appeared to improve outcomes in immunocompromised children provide the rationale for assessing calfactant therapy in this patient population. Funding Source - FDA Office of Orphan Products Development (OOPD)

Official Title
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A Phase 3 Trial of Calfactant for ALI in Pediatric Leukemia and HSCT Patients

Conditions
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Acute Lung Injury

Intervention / Treatment
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* Drug: Calfactant
* Other: Air placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must meet criteria for acute lung injury Intubated, mechanically ventilated, with respiratory failure secondary to diffuse, bilateral parenchymal lung disease (as judged by chest x-ray). Oxygenation index (OI) > 13, but < 37, for two consecutive blood gases which should be separated by at least one hour within 48 hours of the initiation of mechanical ventilation. Arterial catheter placement Parental informed consent Patients must have a diagnosis of leukemia/lymphoma undergoing active treatment or following HSCT for any indication. Leukemia/lymphoma will be defined according to the National Cancer Institute Surveillance Epidemiology and End Results Collaborative Staging Manual including those conditions defined as borderline such as myelodysplastic syndromes. All forms of HSCT will be eligible, allogeneic as well as autologous. Exclusion Criteria: Clinical diagnosis of congestive heart failure and/or pulmonary capillary wedge pressure >15 mmHg, or uncorrected congenital heart disease. Glasgow Coma Score < 8 (prior to respiratory failure). Pre-existing limitations on care options, (Do Not Attempt Resuscitation Orders, etc). Patients with impending death from another disease. Patients moribund or with other organ failure at possible randomization: hypotension unresponsive to treatment (mean BP < 60 or < 5th % for age), persistent cardiac tachyarrhythmia >150/minute, or persistent bradyarrythmia < 50/minute, or age appropriate criteria for younger children, metabolic acidosis > - 10 milliequivalent (mEq)/L for more than 2 hours, persistent arterial oxygen desaturation, arterial partial pressure of oxygen (PaO2) < 50 or oxygen saturation (SaO2) saturation < 80%, hyperkalemia, serum K+ > 6.5 plus widening of QRS complex on EKG (QRS complex corresponds to the depolarization of the right and left ventricles of the heart).

Ages Eligible for Study
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Minimum Age: 18 Months
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Calfactant<br>Endotracheal calfactant administration | Drug: Calfactant<br>* Endotracheal calfactant, up to 3 doses if subject qualifies<br>|
| Placebo Comparator: Placebo (air)<br>Endotracheal air administration | Other: Air placebo<br>* Endotracheal air administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause Mortality at the Time of Pediatric Intensive Care Unit (PICU) Discharge | Overall mortality rate from admission to PICU discharge | Admission to PICU discharge, up to 120 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilator Free Days (VFDs) | Number of days the patient is alive and off of the ventilator | 60 days after study enrollment | 
| Total Duration of Stay Required | Length of stay (LOS) ,measured in days, from admission to PICU discharge and admission to hospital discharge. | Admission to discharge, up to 120 days | 
| Change in Oxygenation: First Intervention | The Oxygenation Index after the first intervention is calculated as the fraction of inspired oxygen, in percent, times the mean airway pressure, in mmHg, divided by the partial pressure of oxygen in arterial blood, in mmHg. Lower values are better. | 48 hours after enrollment, up to 12 hours after each intervention | 
| Change in Oxygenation: Second Intervention | The Oxygenation Index after the second intervention (if applicable) is calculated as the fraction of inspired oxygen, in percent, times the mean airway pressure, in mmHg, divided by the partial pressure of oxygen in arterial blood, in mmHg. Lower values are better. | 48 hours after enrollment, up to 12 hours after each intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Lung Injury, Cancer, Pediatrics