RCT of Olanzapine for Control of CIV in Children Receiving Highly Emetogenic Chemotherapy

Randomized Controlled Trial of Olanzapine for the Control of Chemotherapy-induced Vomiting in Children Receiving Highly Emetogenic Chemotherapy

Chemotherapy-induced nausea and vomiting (CINV) are among the most bothersome symptoms during cancer treatment according to children and their parents. Most children receiving highly emetogenic chemotherapy (HEC), including those receiving hematopoietic stem cell transplant (HSCT) conditioning, experience CIV despite receiving antiemetic prophylaxis. Olanzapine improves CINV control in adult cancer patients, has a track record of safe use in children with psychiatric illness, does not interact with chemotherapy and is inexpensive. We hypothesize that the addition of olanzapine to standard antiemetics will improve chemotherapy-induced vomiting (CIV) control in children receiving highly emetogenic chemotherapy

Study Overview

• Status: Recruiting
• Conditions: Nausea; Oncology; Hematopoietic System--Cancer; Vomiting in Infants and/or Children
• Intervention / Treatment: Drug: Olanzapine; Drug: Placebo Oral Tablet

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Muhammad Ali, MD; Phone Number: 201438 416-813-7654; Email: muhammad.ali@sickkids.ca
• Study Contact Backup: Name: Lee Dupuis, RPh, PhD; Phone Number: 416-813-7762; Email: lee.dupuis@sickkids.ca

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • Recruiting
      • Cancer Care Manitoba
      • Contact: Kathy Hjalmarsson; Email: khjalmarsson@cancercare.mb.ca
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Recruiting
      • Hospital for Sick Children
      • Contact: Lee Dupuis, PhD; Phone Number: 309355 416-813-7654; Email: lee.dupuis@sickkids.ca
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • Terminated
      • Centre Hospitalier Universitaire Sainte-Justine,
• India
  • National Capital Territory of Delhi
    • New Delhi, National Capital Territory of Delhi, India, 110029
      • Recruiting
      • All India Institute of Medical Sciences
      • Contact: Shuvadeep Ganguly; Email: Ganguly.Shuvadeep@gmail.com
• United States
  • California
    • San Francisco, California, United States, 94158
      • Recruiting
      • University of California
      • Contact: Kevin wu; Email: Kevin.Wu3@ucsf.edu
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Recruiting
      • The Children's Mercy Hospital
      • Contact: Judy Vun; Phone Number: (816) 302-6797
  • New York
    • New York, New York, United States, 10032
      • Withdrawn
      • Columbia University/Morgan Stanley Children's Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7220
      • Recruiting
      • University of North Carolina at Chapel Hill
      • Contact: Juanita Cuffee; Phone Number: (919) 966-0017; Email: cuffee@med.unc.edu
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Recruiting
      • Nationwide Children's Hospital
      • Contact: Clelie Peck; Email: clelie.peck@nationwidechildrens.org
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
      • Contact: Shanta Salzer; Phone Number: 843-792-1463

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Planned receipt of HEC or cyclophosphamide ≥ 1 g/m2/day (≥ 33 mg/kg/day) for cancer treatment or autologous or allogeneic HSCT conditioning.81,82 Examples of HEC are: busulfan IV (myeloablative dosing), carboplatin ≥175mg/m²/dose, cisplatin ≥12mg/m²/dose, cytarabine ≥3g/m²/day, melphalan >140mg/m², methotrexate ≥12g/m²/dose and thiotepa ≥300mg/m²/dose.

Plan for inpatient admission from administration of first study drug dose until 24 hours following administration of last study drug dose.

Body weight of at least 12.5 kg

2.5 to < 18 years of age. Note that the minimum age requirement corresponds to an approximate body weight of 12.5 kg.

Samples for all laboratory tests will be obtained within one week prior to administration of the first chemotherapy dose of the study chemotherapy block or the first HSCT conditioning dose:

• Plasma creatinine within 1.5 times the upper limit of normal for age.
• Amylase within age-appropriate limits
• Plasma conjugated bilirubin within ≤ 3x upper limit of normal for age unless attributable to Gilbert's Syndrome
• ALT ≤ 5x upper limit of normal for age

Baseline ECG within the month prior to study drug administration without known clinically significant abnormalities including pathologic prolongation of QTc

A plan for scheduled, round-the-clock receipt of ondansetron, granisetron or palonosetron for antiemetic prophylaxis during administration of chemotherapy or HSCT conditioning.

Negative pregnancy test if female of childbearing potential

Patients of childbearing potential must consent to use adequate contraception (males and females) or agree to practice abstinence

Parent or child able to speak a language in which the (modified Pediatric Adverse Event Rating Scale (PAERS) is available.

Optional: Child participants in the optional assessment of nausea severity must be 4 to 18 years of age. Child and a parent/guardian must be English, Spanish or French-speaking. The Pediatric Nausea Assessment Tool58 (PeNAT) is validated in English-speaking children 4 to 18 years old with an English-speaking parent/guardian and has been translated into Spanish and French. The MAT is available in English, Spanish and French.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Olanzapine; Standard antiemetics plus olanzapine	Drug: Olanzapine; olanzapine 0.1 mg/kg/dose (maximum 10 mg/dose) by mouth as a single daily dose based on actual body weight
Placebo Comparator: Placebo Oral Tablet; Standard antiemetics plus placebo	Drug: Placebo Oral Tablet; Placebo tablets that look like olanzapine and will be dosed as if they are olanzapine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of CIV control during the acute phase	Complete CIV control is no vomiting/retching and no use of breakthrough antiemetic agents during phase	up to 8 days
Rate of CIV control during the acute phase	Partial control is defined as no more than two vomits or retches during any 24-hr period	up to 8 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety profile of olanzapine based on toxicities	Based on descriptive statistics on reported toxicities.	up to 1 month
Safety profile of olanzapine based on weight	Based on descriptive statistics on reported body weight	up to 1 month
Safety profile of olanzapine based on Pediatric Adverse Event Rating Scale (PAERs)	Based on descriptive statistics on reported PAERs, will describe the most reported and most bothersome adverse events reported in the PAERs questionnaire.	up to 1 month
Safety profile of olanzapine based on prolactin	Based on descriptive statistics on reported prolactin, will report incidence of abnormal prolactin values comparing the two arms	up to 1 month
Safety profile of olanzapine based on amylase	Based on descriptive statistics on reported amylase, will report incidence of abnormal amylase values comparing the two arms	up to 1 month
Safety profile of olanzapine based on creatine phophotase	Based on descriptive statistics on reported creatine phophotase, will report incidence of abnormal creatine phophotase values comparing the two arms	up to 1 month
Safety profile of olanzapine based on triglycerides	Based on descriptive statistics on reported triglycerides, will report incidence of abnormal triglyceride values comparing the two arms	up to 1 month
Impact of olanzapine on HSCT outcomes on incidence of veno-occlusive disease	Looking at incidence of veno-occlusive disease	From first HSCT conditioning dose until 100 days post-HSCT
Impact of olanzapine on HSCT outcomes on incidence of GVHD	Looking at incidence of GVHD between the two arms	From first HSCT conditioning dose until 100 days post-HSCT
Impact of olanzapine on HSCT outcomes on severity of GVHD	Comparing the incidence of the different maximal grades of GVHD between the two arms	From first HSCT conditioning dose until 100 days post-HSCT
Association between PeNAT and MASCC Antiemesis Tool (MAT) scores	taking maximum daily PeNAT scale score and maximum nausea experience in MAT will estimate the degree of association between PeNAT and MAT	up to 1 month
complete and partial CINV control	Complete CIV control is no vomiting/retching and no use of breakthrough antiemetic agents during phase, Partial control is defined as no more than two vomits or retches during any 24-hr period	up to 1 month

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Collaborators: Medical University of South Carolina; Columbia University; University of California, San Francisco; Nationwide Children's Hospital; University of North Carolina, Chapel Hill; Children's Mercy Hospital Kansas City; St. Justine's Hospital; CancerCare Manitoba
• Investigators: Principal Investigator: Lee Dupuis, RPh, PhD, The Hospital for Sick Children; Principal Investigator: Muhammad Ali, MD, The Hospital for Sick Children

Publications and helpful links

General Publications

• Dupuis LL, Taddio A, Kerr EN, Kelly A, MacKeigan L. Development and validation of the pediatric nausea assessment tool for use in children receiving antineoplastic agents. Pharmacotherapy. 2006 Sep;26(9):1221-31. doi: 10.1592/phco.26.9.1221.

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2017
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: March 16, 2017
• First Submitted That Met QC Criteria: April 13, 2017
• First Posted (Actual): April 18, 2017

Study Record Updates

• Last Update Posted (Estimated): October 8, 2025
• Last Update Submitted That Met QC Criteria: October 3, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: children; olanzapine; adolescents; vomiting; supportive care; bone marrow transplant
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neoplasms; Nausea; Vomiting; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzazepines; Benzodiazepines; Olanzapine
• Other Study ID Numbers: 1000053716

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes