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

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ClinicalTrials.gov Identifier: NCT03118986
Recruitment Status : Recruiting
First Posted : April 18, 2017
Last Update Posted : August 29, 2017
Sponsor:
Information provided by (Responsible Party):
Lee Dupuis, The Hospital for Sick Children

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 high dose cyclophosphamide for hematopoietic stem cell transplantation (HSCT) conditioning.

Condition or disease Intervention/treatment Phase
Vomiting in Infants and/or Children Nausea Hematopoietic System--Cancer Drug: Olanzapine Drug: Placebo Oral Tablet Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Supportive Care
Official Title: Randomized Controlled Trial of Olanzapine for the Control of Chemotherapy-induced Vomiting in Children Receiving Cyclophosphamide-based Conditioning for Allogeneic Hematopoietic Stem Cell Transplant
Actual Study Start Date : August 10, 2017
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : November 2021

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. Safety profile of olanzapine based on toxicities [ Time Frame: up to 1 month ]
    Based on descriptive statistics on reported toxicities.

  3. Safety profile of olanzapine based on weight [ Time Frame: up to 1 month ]
    Based on descriptive statistics on reported body weight

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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



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Ages Eligible for Study:   30 Months to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Planned allogeneic HSCT with a conditioning regimen that includes cyclophosphamide ≥ 1 g/m^2/day (≥ 33 mg/kg/day)
  • Planned to receive either cyclosporine or tacrolimus for acute GVHD prophylaxis.
  • 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.
  • 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 and unconjugated bilirubin within ≤ 1.5x upper limit of normal for age unless attributable to Gilbert's Syndrome
  • Plasma triglycerides within age appropriate limits
  • ALT ≤ 3x upper limit of normal for age
  • AST ≤ 3x 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
  • English-speaking parent or child (PAERS is available only in English)
  • 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-speaking. The PeNAT is validated only in English-speaking children 4 to 18 years old with an English-speaking parent/guardian.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03118986


Contacts
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

Locations
Canada, Ontario
Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Lee Dupuis, PhD    416-813-7654 ext 309355    lee.dupuis@sickkids.ca   
Sponsors and Collaborators
The Hospital for Sick Children
Investigators
Principal Investigator: Lee Dupuis, RPh, PhD The Hospital for Sick Children
Principal Investigator: Tal Schechter-Finkelstein, MD The Hospital for Sick Children

Publications:
Responsible Party: Lee Dupuis, Principal Investigator, The Hospital for Sick Children
ClinicalTrials.gov Identifier: NCT03118986     History of Changes
Other Study ID Numbers: 1000053716
First Posted: April 18, 2017    Key Record Dates
Last Update Posted: August 29, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by Lee Dupuis, The Hospital for Sick Children:
olanzapine
vomiting
children
adolescents
bone marrow transplant
supportive care

Additional relevant MeSH terms:
Vomiting
Signs and Symptoms, Digestive
Signs and Symptoms
Olanzapine
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents