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

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

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)

Study Overview

• Status: Completed
• Conditions: Acute Lung Injury
• Intervention / Treatment: Drug: Calfactant; Other: Air placebo

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada
      • Hospital Sainte Justine
• United States
  • Arizona
    • Phoenix, Arizona, United States
      • Phoenix Children's Hospital
  • California
    • Los Angeles, California, United States
      • Children's Hospital of Los Angeles
    • San Francisco, California, United States
      • University of California San Francisco
  • Indiana
    • Indianapolis, Indiana, United States
      • Riley Children's Hospital
  • New Jersey
    • Hackensack, New Jersey, United States
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States
      • Weill Cornell Medical Center
    • Valhalla, New York, United States
      • Maria Fareri Children's Hospital
  • Ohio
    • Cleveland, Ohio, United States
      • Rainbow Babies Hospital
    • Columbus, Ohio, United States
      • Nationwide Children's Hospital
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17078
      • Penn State College of Medicine, Penn State Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States
      • Children's Hospital of Pittsburgh
  • Tennessee
    • Memphis, Tennessee, United States
      • St. Jude Children's Research Hospital
  • Texas
    • Houston, Texas, United States
      • Texas Children's Hospital
  • Wisconsin
    • Milwaukee, Wisconsin, United States
      • Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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
2. 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:

1. Clinical diagnosis of congestive heart failure and/or pulmonary capillary wedge pressure >15 mmHg, or uncorrected congenital heart disease.
2. Glasgow Coma Score < 8 (prior to respiratory failure).
3. Pre-existing limitations on care options, (Do Not Attempt Resuscitation Orders, etc).
4. Patients with impending death from another disease.

5. 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Milton S. Hershey Medical Center
• Investigators: Principal Investigator: Neal J Thomas, MD, MSc, Penn State College of Medicine, Penn State Milton S. Hershey Medical Center; Principal Investigator: Robert F Tamburro, MD, MSc, Penn State College of Medicine, Penn State Milton S. Hershey Medical Center

Publications and helpful links

General Publications

• Willson DF, Thomas NJ, Markovitz BP, Bauman LA, DiCarlo JV, Pon S, Jacobs BR, Jefferson LS, Conaway MR, Egan EA; Pediatric Acute Lung Injury and Sepsis Investigators. Effect of exogenous surfactant (calfactant) in pediatric acute lung injury: a randomized controlled trial. JAMA. 2005 Jan 26;293(4):470-6. doi: 10.1001/jama.293.4.470. Erratum In: JAMA. 2005 Aug 24;294(8):900.
• Tamburro RF, Thomas NJ, Pon S, Jacobs BR, Dicarlo JV, Markovitz BP, Jefferson LS, Willson DF; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Post hoc analysis of calfactant use in immunocompromised children with acute lung injury: Impact and feasibility of further clinical trials. Pediatr Crit Care Med. 2008 Sep;9(5):459-64. doi: 10.1097/PCC.0b013e3181849bec.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: October 18, 2009
• First Submitted That Met QC Criteria: October 21, 2009
• First Posted (Estimate): October 22, 2009

Study Record Updates

• Last Update Posted (Actual): March 16, 2018
• Last Update Submitted That Met QC Criteria: February 15, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Cancer; Pediatrics; Acute Lung Injury
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Wounds and Injuries; Thoracic Injuries; Acute Lung Injury; Lung Injury; Respiratory System Agents; Pulmonary Surfactants; Calfactant
• Other Study ID Numbers: 1R01FD003410-01 (U.S. FDA Grant/Contract); R01FD003410-01A1 (U.S. FDA Grant/Contract)