Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

RCT of Olanzapine for Control of CIV in Children Receiving HSCT Conditioning

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03118986
Recruitment Status : Recruiting
First Posted : April 18, 2017
Last Update Posted : February 3, 2021
Sponsor:
Collaborators:
University of California, San Francisco
Children's Mercy Hospital Kansas City
St. Justine's Hospital
Columbia University
Medical University of South Carolina
Information provided by (Responsible Party):
Lee Dupuis, The Hospital for Sick Children

Tracking Information
First Submitted Date  ICMJE March 16, 2017
First Posted Date  ICMJE April 18, 2017
Last Update Posted Date February 3, 2021
Actual Study Start Date  ICMJE August 10, 2017
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 25, 2017)
Rate of CIV control during the acute phase [ Time Frame: up to 8 days ]
Complete CIV control is no vomiting/retching and no use of breakthrough antiemetic agents during phase
Original Primary Outcome Measures  ICMJE
 (submitted: April 13, 2017)
Rate of complete chemotherapy induced vomiting (CIV) control during the acute phase [ Time Frame: up to 8 days ]
Complete CIV control is no vomiting/retching and no use of breakthrough antiemetic agents during phase
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 25, 2017)
  • complete CINV control [ Time Frame: up to 1 month ]
    CINV control - no vomiting/retching and no nausea (Pediatric Nausea Assessment Tool [PeNAT] score=1) during phase of interest
  • Safety profile of olanzapine based on toxicities [ Time Frame: up to 1 month ]
    Based on descriptive statistics on reported toxicities.
  • Safety profile of olanzapine based on weight [ Time Frame: up to 1 month ]
    Based on descriptive statistics on reported body weight
  • Safety profile of olanzapine based on Pediatric Adverse Event Rating Scale (PAERs) [ Time Frame: up to 1 month ]
    Based on descriptive statistics on reported PAERs, will describe the most reported and most bothersome adverse events reported in the PAERs questionnaire.
  • Safety profile of olanzapine based on prolactin [ Time Frame: up to 1 month ]
    Based on descriptive statistics on reported prolactin, will report incidence of abnormal prolactin values comparing the two arms
  • Safety profile of olanzapine based on amylase [ Time Frame: up to 1 month ]
    Based on descriptive statistics on reported amylase, will report incidence of abnormal amylase values comparing the two arms
  • Safety profile of olanzapine based on creatine phophotase [ Time Frame: up to 1 month ]
    Based on descriptive statistics on reported creatine phophotase, will report incidence of abnormal creatine phophotase values comparing the two arms
  • Safety profile of olanzapine based on triglycerides [ Time Frame: up to 1 month ]
    Based on descriptive statistics on reported triglycerides, will report incidence of abnormal triglyceride values comparing the two arms
  • Impact of olanzapine on HSCT outcomes on incidence of veno-occlusive disease [ Time Frame: From first HSCT conditioning dose until 100 days post-HSCT ]
    Looking at incidence of veno-occlusive disease
  • Impact of olanzapine on HSCT outcomes on incidence of GVHD [ Time Frame: From first HSCT conditioning dose until 100 days post-HSCT ]
    Looking at incidence of GVHD between the two arms
  • Impact of olanzapine on HSCT outcomes on severity of GVHD [ Time Frame: From first HSCT conditioning dose until 100 days post-HSCT ]
    Comparing the incidence of the different maximal grades of GVHD between the two arms
  • Association between PeNAT and MASCC Antiemesis Tool (MAT) scores [ Time Frame: up to 1 month ]
    taking maximum daily PeNAT scale score and maximum nausea experience in MAT will estimate the degree of association between PeNAT and MAT
Original Secondary Outcome Measures  ICMJE
 (submitted: April 13, 2017)
  • complete CINV control [ Time Frame: up to 1 month ]
    CINV control - no vomiting/retching and no nausea (PeNAT score=1) during phase of interest
  • Safety profile of olanzapine based on toxicities [ Time Frame: up to 1 month ]
    Based on descriptive statistics on reported toxicities. Will describe the number of incidence of common toxicities reported
  • Safety profile of olanzapine based on weight [ Time Frame: up to 1 month ]
    Based on descriptive statistics on reported body weight
  • Safety profile of olanzapine based on PAERs [ Time Frame: up to 1 month ]
    Based on descriptive statistics on reported PAERs, will describe the most reported and most bothersome adverse events reported in the PAERs questionnaire.
  • Safety profile of olanzapine based on prolactin [ Time Frame: up to 1 month ]
    Based on descriptive statistics on reported prolactin, will report incidence of abnormal prolactin values comparing the two arms
  • Safety profile of olanzapine based on amylase [ Time Frame: up to 1 month ]
    Based on descriptive statistics on reported amylase, will report incidence of abnormal amylase values comparing the two arms
  • Safety profile of olanzapine based on creatine phophotase [ Time Frame: up to 1 month ]
    Based on descriptive statistics on reported creatine phophotase, will report incidence of abnormal creatine phophotase values comparing the two arms
  • Safety profile of olanzapine based on triglycerides [ Time Frame: up to 1 month ]
    Based on descriptive statistics on reported triglycerides, will report incidence of abnormal triglyceride values comparing the two arms
  • Impact of olanzapine on HSCT outcomes on incidence of veno-occlusive disease [ Time Frame: From first HSCT conditioning dose until 100 days post-HSCT ]
    Looking at incidence of veno-occlusive disease
  • Impact of olanzapine on HSCT outcomes on incidence of GVHD [ Time Frame: From first HSCT conditioning dose until 100 days post-HSCT ]
    Looking at incidence of GVHD between the two arms
  • Impact of olanzapine on HSCT outcomes on severity of GVHD [ Time Frame: From first HSCT conditioning dose until 100 days post-HSCT ]
    Comparing the incidence of the different maximal grades of GVHD between the two arms
  • Association between PeNAT and MAT scores [ Time Frame: up to 1 month ]
    taking maximum daily PeNAT scale score and maximum nausea experience in MAT will estimate the degree of association between PeNAT and MAT
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE RCT of Olanzapine for Control of CIV in Children Receiving HSCT Conditioning
Official Title  ICMJE Randomized Controlled Trial of Olanzapine for the Control of Chemotherapy-induced Vomiting in Children Receiving Chemotherapy for Hematopoietic Stem Cell Transplant Conditioning
Brief Summary Chemotherapy-induced nausea and vomiting (CINV) are among the most bothersome symptoms during cancer treatment according to children and their parents. Most children receiving hematopoietic stem cell transplant (HSCT) conditioning experience CINV 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 chemotherapy for HSCT conditioning.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Supportive Care
Condition  ICMJE
  • Vomiting in Infants and/or Children
  • Nausea
  • Hematopoietic System--Cancer
Intervention  ICMJE
  • Drug: Olanzapine
    olanzapine 0.1 mg/kg/dose (maximum 10 mg/dose) by mouth as a single daily dose based on actual body weight
  • Drug: Placebo Oral Tablet
    Placebo tablets that look like olanzapine and will be dosed as if they are olanzapine
Study Arms  ICMJE
  • Active Comparator: Olanzapine
    Standard antiemetics plus olanzapine
    Intervention: Drug: Olanzapine
  • Placebo Comparator: Placebo Oral Tablet
    Standard antiemetics plus placebo
    Intervention: Drug: Placebo Oral Tablet
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 13, 2017)
200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2023
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Planned autologous or allogeneic HSCT with a conditioning regimen that includes cyclophosphamide ≥ 1 g/m^2/day (≥ 33 mg/kg/day) or highly emetogenic chemotherapy (HEC)
  • Body weight of at least 12.5 kg
  • 2.5 to 18 years of age. Note that the minimum body weight requirement corresponds to approximately a 2.5 year old.
  • A baseline ECG within the month prior to the study drug administration without known clinically significant abnormalities including pathologic prolongation of QTC.
  • Samples for all laboratory tests will be obtained within one week prior to administration of the first dose of HSCT conditioning:
  • 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
  • A plan for scheduled, round-the-clock receipt of ondansetron, granisetron or palonosetron for antiemetic prophylaxis during administration of 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 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.

Exclusion Criteria:

  • CNS malignancy, either primary CNS tumor or CNS metastases. A history of CNS leukemia, in remission at study entry, is allowed.
  • Pre-existing seizure disorder; known cardiac arrhythmias; known clinically significant ECG abnormalities at baseline including QTc prolongation; uncontrolled diabetes mellitus; history of neuroleptic malignant syndrome; known hypersensitivity or allergy to olanzapine.
  • Treatment within 14 days prior to the first day of study drug administration with olanzapine or other anti-psychotic agents (e.g. risperidone, quetiapine, aripiprazole, clozapine, butyrophenone) including those used to control CINV (e.g. chlorpromazine, prochlorperazine, promethazine)
  • Scheduled administration (i.e. not PRN) of antiemetics other than dexamethasone and ondansetron, granisetron or palonosetron is not permitted.

Scopolamine patches, aprepitant, fosaprepitant, phenothiazines (e.g. chlorpromazine, prochlorperazine), acupressure or acupuncture are not permitted during the acute and delayed phases. Methylprednisolone and hydrocortisone are permitted during the acute and delayed phases for prevention or treatment of reaction (e.g. thymoglobulin, alemtuzumab, blood products) and during delayed phase for GVHD prophylaxis. Administration of olanzapine other than ordered as per study procedures is not permitted. However, other antiemetics may be administered as needed (PRN) for treatment of breakthrough CINV. For patients receiving busulfan, scheduled administration of benzodiazepines such as lorazepam for seizure prophylaxis is permitted on the days that busulfan is given and for 24 hours after.

  • Receipt of cranial boost radiation within 14 days of the first day of HSCT conditioning.
  • Planned co-administration of citalopram, amifostine, medications known to alter the metabolism of olanzapine (e.g. ciprofloxacin, valproic acid)
  • Previous participation in this study.
  • Participants in the optional assessment of nausea severity must be free of cognitive, hearing or visual impairment that preclude completion of the PeNAT.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Months to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lee Dupuis, RPh, PhD 416-813-7654 ext 309355 lee.dupuis@sickkids.ca
Contact: Tal Schechter-Finkelstein, MD 416-813-6906 ext 206906 tal.schechter-finkelstein@sickkids.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03118986
Other Study ID Numbers  ICMJE 1000053716
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Lee Dupuis, The Hospital for Sick Children
Study Sponsor  ICMJE The Hospital for Sick Children
Collaborators  ICMJE
  • University of California, San Francisco
  • Children's Mercy Hospital Kansas City
  • St. Justine's Hospital
  • Columbia University
  • Medical University of South Carolina
Investigators  ICMJE
Principal Investigator: Lee Dupuis, RPh, PhD The Hospital for Sick Children
Principal Investigator: Tal Schechter-Finkelstein, MD The Hospital for Sick Children
PRS Account The Hospital for Sick Children
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP