<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02979548</url>
  </required_header>
  <id_info>
    <org_study_id>IECPG-419</org_study_id>
    <nct_id>NCT02979548</nct_id>
  </id_info>
  <brief_title>Study to Evaluate the Effect of Aprepitant in Children and Adolescents Receiving AML Remission Induction Chemotherapy</brief_title>
  <official_title>Study to Evaluate the Anti-emetic Effect of Aprepitant as an add-on Therapy in Children and Adolescents Receiving AML Remission Induction Chemotherapy: An Investigator-initiated, Randomized, Open Label Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dr Atul Sharma</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>All India Institute of Medical Sciences, New Delhi</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to find out the efficacy of an anti-emetic drug, Aprepitant as an&#xD;
      add-on therapy to prevent vomiting in children and adolescents receiving chemotherapy for&#xD;
      leukemia (AML).&#xD;
&#xD;
      Children and adolescents admitted with confirmed diagnosis of AML will be assessed for&#xD;
      eligibility criteria and enrolled in the study. Then they will be divided (randomized) into&#xD;
      experimental and control groups.&#xD;
&#xD;
      Experimental group will receive Aprepitant capsules 1 h prior to chemotherapy on days 1-3 in&#xD;
      addition to ondansetron. Patients will be required to swallow the whole capsule and opening&#xD;
      of capsule will not be permitted. All three doses will be administered under supervision.&#xD;
&#xD;
      Control group will receive ondansetron (0.15 mg/kg) as an intravenous bolus 30 minutes before&#xD;
      chemotherapy followed by every 8 hourly for 8 days. Metoclopramide will be used as a rescue&#xD;
      agent.&#xD;
&#xD;
      The data will be collected from each patient in a proforma from day 1 to day 13 of&#xD;
      chemotherapy. A Diary will be maintained for nausea and vomiting record.&#xD;
&#xD;
      Edmonton's symptom assessment criterion will be used in the diary for assessing severity of&#xD;
      nausea. The NCI guidelines will be used to assess the severity of vomiting based on the data&#xD;
      provided by the patient in the diary.&#xD;
&#xD;
      A modified intention-to-treat population (patients who receive chemotherapy, take one or more&#xD;
      doses of study drug, and have one or more post treatment measurements) will be used for&#xD;
      efficacy analysis. Proportion of patients with complete response will be compared between&#xD;
      patients with or without aprepitant.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Children and adolescents admitted with confirmed diagnosis of AML will be assessed for&#xD;
      eligibility criteria and enrolled in the study. Subjects will be randomized into experimental&#xD;
      and control groups using table of random numbers generated by computer.Experimental group&#xD;
      will receive aprepitant capsules as an add-on therapy (Apretero; Hetero Laboratories, India)&#xD;
      1 h prior to chemotherapy on days 1-3 in addition to ondansetron.&#xD;
&#xD;
      The dose of aprepitant will be as per our previous study based on weight groups'&#xD;
&#xD;
        -  Weight 15-40 kg : Aprepitant 80 mg on days 1-3&#xD;
&#xD;
        -  Weight &gt; 41kg: Aprepitant 125 mg on day 1 followed by 80 mg on days 2-3 Patients will be&#xD;
           required to swallow the whole capsule and opening of capsule will not be permitted.&#xD;
&#xD;
      All three doses will be administered under supervision by the sister allocated. Control group&#xD;
      will receive ondansetron (0.15 mg/kg) as an intravenous bolus 30 minutes before chemotherapy&#xD;
      followed by every 8 hourly. Metoclopramide will be used as a rescue agent.&#xD;
&#xD;
      The data will be collected from each patient in a proforma from day 1 to day 13 of&#xD;
      chemotherapy by the investigator during his/her stay as in-patient in the hospital. The&#xD;
      Proforma will contain different items dealing with demographic and clinical characteristic of&#xD;
      the subjects.A Diary will be maintained for nausea and vomiting record. It will help in&#xD;
      collecting data regarding nausea, vomiting along with some additional variables like-&#xD;
      chemotherapy related toxicities, requirement of any rescue medication.&#xD;
&#xD;
      The subjects will be given the diary for symptom assessment on day 1 and it will be filled up&#xD;
      under the supervision of the investigator on day 1 and day 2 of chemotherapy. The diary will&#xD;
      be given to the subjects on day 3 of the chemotherapy to record all the events (incidence and&#xD;
      severity of nausea, vomiting, requirement of rescue medication and other toxicities).&#xD;
&#xD;
      Edmonton's symptom assessment criterion will be used in the diary for assessing severity of&#xD;
      nausea. The NCI guidelines will be used to assess the severity of vomiting based on the data&#xD;
      provided by the patient in the diary.Patients/attendant's will be explained about the filling&#xD;
      of the diary and will maintain it for recording of vomiting under the investigator's&#xD;
      supervision.&#xD;
&#xD;
      A modified intention-to-treat population (patients who receive chemotherapy, take one or more&#xD;
      doses of study drug, and have one or more post treatment measurements) will be used for&#xD;
      efficacy analysis.Proportion of patients with CR will be compared between patients with or&#xD;
      without aprepitant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>November 2016</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">June 2018</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of patients with complete response during the acute phase of AML remission induction chemotherapy</measure>
    <time_frame>Up to day 8 of induction</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to first episode of vomiting</measure>
    <time_frame>Up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of delayed vomiting</measure>
    <time_frame>From day 9 to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of vomiting</measure>
    <time_frame>Up to day 13</time_frame>
    <description>Severity will be assessed by NCI CTCAE Criteria version 4.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of requirement of rescue medication</measure>
    <time_frame>Up to day 8</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">116</enrollment>
  <condition>Chemotherapy Induced Vomiting</condition>
  <condition>Acute Myeloid Leukemia</condition>
  <arm_group>
    <arm_group_label>Group A : Aprepitant (Add on therapy)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Aprepitant group will receive aprepitant capsules 1 h prior to chemotherapy on days 1-3 in addition to 5HT3 RA (Ondansetron). The dose of aprepitant will be given based on weight groups Weight 15-40 kg : Aprepitant 80 mg on days 1-3 Weight &gt; 41kg: Aprepitant 125 mg on day 1 followed by 80 mg on days 2-3 Rescue medication, injection metoclopramide 0.5 mg/kg body weight/day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B : 5HT3 RA (Ondansetron)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>On the day of chemotherapy, ondansetron will be administered to all patients as per our institutional practice in a dose of 0.15 mg/kg as an intravenous bolus 30 minutes before chemotherapy followed by every 8 hourly for 8 days.&#xD;
Rescue medication, injection metoclopramide 0.5 mg/kg body weight/day.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aprepitant</intervention_name>
    <description>Aprepitant is a non peptide, selective, Neurokinin type 1 (NK 1) receptor antagonist. Group A will receive Aprepitant as an add-on anti-emetic therapy in addition to ondansetron.</description>
    <arm_group_label>Group A : Aprepitant (Add on therapy)</arm_group_label>
    <other_name>Apretero</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ondansetron</intervention_name>
    <description>Ondansetron is 5HT3 Receptor antagonist used to treat and prevent chemotherapy induced nausea and vomiting</description>
    <arm_group_label>Group A : Aprepitant (Add on therapy)</arm_group_label>
    <arm_group_label>Group B : 5HT3 RA (Ondansetron)</arm_group_label>
    <other_name>Zofer, Emset</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metoclopramide</intervention_name>
    <description>Dopamine receptor antagonist , acts at CTZ. Rescue medication, injection metoclopramide 0.5 mg/kg body weight/day.</description>
    <arm_group_label>Group A : Aprepitant (Add on therapy)</arm_group_label>
    <arm_group_label>Group B : 5HT3 RA (Ondansetron)</arm_group_label>
    <other_name>Reglan</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Newly diagnosed, chemotherapy-naïve de novo AML patients planned for 3+7 remission&#xD;
             induction chemotherapy in the age group 5-18 years&#xD;
&#xD;
          2. Weight above 15 kg (Those who are able to swallow the medication )&#xD;
&#xD;
          3. Children/adolescents and their caregiver who can understand Hindi or English and&#xD;
             willing to participate in the study (with written informed consent)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Vomiting/retching within 24 h prior to treatment&#xD;
&#xD;
          2. Significant organ dysfunction (aspartate aminotransferase/alanine aminotransferase&#xD;
             &gt;2.5 times of upper normal limit, serum bilirubin &gt;1.5 times of upper normal limit,&#xD;
             serum creatinine&gt;1.5 times of upper normal limit)&#xD;
&#xD;
          3. Patient on inotropic support at presentation&#xD;
&#xD;
          4. Patient with respiratory failure/mechanical ventilation at presentation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>5 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Atul Sharma, M.D</last_name>
    <phone>+91-9968859779</phone>
    <email>dratulsharma@hotmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Irch, Aiims , New Delhi , India</name>
      <address>
        <city>New Delhi</city>
        <state>DEL</state>
        <zip>110029</zip>
        <country>India</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>ATUL SHARMA, MD</last_name>
      <phone>9968859779</phone>
      <email>dratulsharma@hotmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>November 28, 2016</study_first_submitted>
  <study_first_submitted_qc>November 29, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 1, 2016</study_first_posted>
  <last_update_submitted>January 24, 2017</last_update_submitted>
  <last_update_submitted_qc>January 24, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 25, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>All India Institute of Medical Sciences, New Delhi</investigator_affiliation>
    <investigator_full_name>Dr Atul Sharma</investigator_full_name>
    <investigator_title>Senior Resident</investigator_title>
  </responsible_party>
  <keyword>Aprepitant</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vomiting</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ondansetron</mesh_term>
    <mesh_term>Aprepitant</mesh_term>
    <mesh_term>Metoclopramide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>It is undecided but if required the data can be made available.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02979548
org study id: IECPG-419
nct id: NCT02979548
lead sponsor: 
has dmc: No
The purpose of the study is to find out the efficacy of an anti-emetic drug, Aprepitant as an
      add-on therapy to prevent vomiting in children and adolescents receiving chemotherapy for
      leukemia (AML).

      Children and adolescents admitted with confirmed diagnosis of AML will be assessed for
      eligibility criteria and enrolled in the study. Then they will be divided (randomized) into
      experimental and control groups.

      Experimental group will receive Aprepitant capsules 1 h prior to chemotherapy on days 1-3 in
      addition to ondansetron. Patients will be required to swallow the whole capsule and opening
      of capsule will not be permitted. All three doses will be administered under supervision.

      Control group will receive ondansetron (0.15 mg/kg) as an intravenous bolus 30 minutes before
      chemotherapy followed by every 8 hourly for 8 days. Metoclopramide will be used as a rescue
      agent.

      The data will be collected from each patient in a proforma from day 1 to day 13 of
      chemotherapy. A Diary will be maintained for nausea and vomiting record.

      Edmonton's symptom assessment criterion will be used in the diary for assessing severity of
      nausea. The NCI guidelines will be used to assess the severity of vomiting based on the data
      provided by the patient in the diary.

      A modified intention-to-treat population (patients who receive chemotherapy, take one or more
      doses of study drug, and have one or more post treatment measurements) will be used for
      efficacy analysis. Proportion of patients with complete response will be compared between
      patients with or without aprepitant.
Children and adolescents admitted with confirmed diagnosis of AML will be assessed for
      eligibility criteria and enrolled in the study. Subjects will be randomized into experimental
      and control groups using table of random numbers generated by computer.Experimental group
      will receive aprepitant capsules as an add-on therapy (Apretero; Hetero Laboratories, India)
      1 h prior to chemotherapy on days 1-3 in addition to ondansetron.

      The dose of aprepitant will be as per our previous study based on weight groups'

        -  Weight 15-40 kg : Aprepitant 80 mg on days 1-3

        -  Weight > 41kg: Aprepitant 125 mg on day 1 followed by 80 mg on days 2-3 Patients will be
           required to swallow the whole capsule and opening of capsule will not be permitted.

      All three doses will be administered under supervision by the sister allocated. Control group
      will receive ondansetron (0.15 mg/kg) as an intravenous bolus 30 minutes before chemotherapy
      followed by every 8 hourly. Metoclopramide will be used as a rescue agent.

      The data will be collected from each patient in a proforma from day 1 to day 13 of
      chemotherapy by the investigator during his/her stay as in-patient in the hospital. The
      Proforma will contain different items dealing with demographic and clinical characteristic of
      the subjects.A Diary will be maintained for nausea and vomiting record. It will help in
      collecting data regarding nausea, vomiting along with some additional variables like-
      chemotherapy related toxicities, requirement of any rescue medication.

      The subjects will be given the diary for symptom assessment on day 1 and it will be filled up
      under the supervision of the investigator on day 1 and day 2 of chemotherapy. The diary will
      be given to the subjects on day 3 of the chemotherapy to record all the events (incidence and
      severity of nausea, vomiting, requirement of rescue medication and other toxicities).

      Edmonton's symptom assessment criterion will be used in the diary for assessing severity of
      nausea. The NCI guidelines will be used to assess the severity of vomiting based on the data
      provided by the patient in the diary.Patients/attendant's will be explained about the filling
      of the diary and will maintain it for recording of vomiting under the investigator's
      supervision.

      A modified intention-to-treat population (patients who receive chemotherapy, take one or more
      doses of study drug, and have one or more post treatment measurements) will be used for
      efficacy analysis.Proportion of patients with CR will be compared between patients with or
      without aprepitant.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Single (Outcomes Assessor)
measure: Proportion of patients with complete response during the acute phase of AML remission induction chemotherapy
time frame: Up to day 8 of induction
measure: Time to first episode of vomiting
time frame: Up to day 13
measure: Incidence of delayed vomiting
time frame: From day 9 to day 13
measure: Severity of vomiting
time frame: Up to day 13
description: Severity will be assessed by NCI CTCAE Criteria version 4.0
measure: Incidence of requirement of rescue medication
time frame: Up to day 8
arm group label: Group A : Aprepitant (Add on therapy)
arm group type: Experimental
description: Aprepitant group will receive aprepitant capsules 1 h prior to chemotherapy on days 1-3 in addition to 5HT3 RA (Ondansetron). The dose of aprepitant will be given based on weight groups Weight 15-40 kg : Aprepitant 80 mg on days 1-3 Weight > 41kg: Aprepitant 125 mg on day 1 followed by 80 mg on days 2-3 Rescue medication, injection metoclopramide 0.5 mg/kg body weight/day.
arm group label: Group B : 5HT3 RA (Ondansetron)
arm group type: Active Comparator
description: On the day of chemotherapy, ondansetron will be administered to all patients as per our institutional practice in a dose of 0.15 mg/kg as an intravenous bolus 30 minutes before chemotherapy followed by every 8 hourly for 8 days.
Rescue medication, injection metoclopramide 0.5 mg/kg body weight/day.
intervention type: Drug
intervention name: Aprepitant
description: Aprepitant is a non peptide, selective, Neurokinin type 1 (NK 1) receptor antagonist. Group A will receive Aprepitant as an add-on anti-emetic therapy in addition to ondansetron.
arm group label: Group A : Aprepitant (Add on therapy)
other name: Apretero
intervention type: Drug
intervention name: Ondansetron
description: Ondansetron is 5HT3 Receptor antagonist used to treat and prevent chemotherapy induced nausea and vomiting
arm group label: Group A : Aprepitant (Add on therapy)
arm group label: Group B : 5HT3 RA (Ondansetron)
other name: Zofer, Emset
intervention type: Drug
intervention name: Metoclopramide
description: Dopamine receptor antagonist , acts at CTZ. Rescue medication, injection metoclopramide 0.5 mg/kg body weight/day.
arm group label: Group A : Aprepitant (Add on therapy)
arm group label: Group B : 5HT3 RA (Ondansetron)
other name: Reglan
criteria: 
gender: All
minimum age: 5 Years
maximum age: 18 Years
healthy volunteers: No
last name: Atul Sharma, M.D
phone: +91-9968859779
email: dratulsharma@hotmail.com
facility: 
status: Recruiting
contact: 
country: India
responsible party type: Sponsor-Investigator
investigator affiliation: All India Institute of Medical Sciences, New Delhi
investigator full name: Dr Atul Sharma
investigator title: Senior Resident
mesh term: Vomiting
mesh term: Ondansetron
mesh term: Aprepitant
mesh term: Metoclopramide
sharing ipd: Undecided
ipd description: It is undecided but if required the data can be made available.