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

Phase 2RecruitingNCT03118986

The Hospital for Sick Children200 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

TRIPLE

Enrollment

200

Conditions

Vomiting in Infants and/or Children Nausea Hematopoietic System--Cancer Oncology

Eligibility

Sex: ALLMin age: 30 MonthsMax age: 18 Years

Medical Language ↔ Plain English

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.

Locations (10)

University of California

San Francisco, California, United States

RECRUITING

The Children's Mercy Hospital

Kansas City, Missouri, United States

RECRUITING

Columbia University/Morgan Stanley Children's Hospital

New York, New York, United States

WITHDRAWN

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, United States

RECRUITING

Medical University of South Carolina

Charleston, South Carolina, United States

RECRUITING

Cancer Care Manitoba

Winnipeg, Manitoba, Canada

RECRUITING

Hospital for Sick Children

Toronto, Ontario, Canada

RECRUITING

Centre Hospitalier Universitaire Sainte-Justine,

Montreal, Quebec, Canada

TERMINATED

All India Institute of Medical Sciences

New Delhi, National Capital Territory of Delhi, India

RECRUITING

Outcomes

Primary Outcomes

Rate of CIV control during the acute phase

Complete CIV control is no vomiting/retching and no use of breakthrough antiemetic agents during phase

Time frame: 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

Time frame: up to 8 days

Secondary Outcomes

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

Time frame: up to 1 month

Safety profile of olanzapine based on toxicities

Based on descriptive statistics on reported toxicities.

Time frame: up to 1 month

Safety profile of olanzapine based on weight

Based on descriptive statistics on reported body weight

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: up to 1 month

Impact of olanzapine on HSCT outcomes on incidence of veno-occlusive disease

Looking at incidence of veno-occlusive disease

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: up to 1 month

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

Overview

Conditions

Interventions

Eligibility

Locations (10)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts