Study to Evaluate the Effect of Aprepitant in Children and Adolescents Receiving AML Remission Induction Chemotherapy

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02979548
• Other study ID #: IECPG-419
• Status: Recruiting
• Phase: Phase 3
• First received: November 28, 2016
• Last updated: January 24, 2017
• Start date: November 2016
• Est. completion date: December 2018

Study information

• Verified date: January 2017
• Source: All India Institute of Medical Sciences, New Delhi
• Contact: Atul Sharma, M.D
• Phone: +91-9968859779
• Email: dratulsharma[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 116
• Est. completion date: December 2018
• Est. primary completion date: June 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 18 Years

Eligibility

Inclusion Criteria:

1. Newly diagnosed, chemotherapy-naïve de novo AML patients planned for 3+7 remission induction chemotherapy in the age group 5-18 years

2. Weight above 15 kg (Those who are able to swallow the medication )

3. Children/adolescents and their caregiver who can understand Hindi or English and willing to participate in the study (with written informed consent)

Exclusion Criteria:

1. Vomiting/retching within 24 h prior to treatment

2. Significant organ dysfunction (aspartate aminotransferase/alanine aminotransferase >2.5 times of upper normal limit, serum bilirubin >1.5 times of upper normal limit, serum creatinine>1.5 times of upper normal limit)

3. Patient on inotropic support at presentation

4. Patient with respiratory failure/mechanical ventilation at presentation

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Chemotherapy Induced Vomiting
• Leukemia, Myeloid, Acute
• Vomiting

Intervention

Drug:
• Aprepitant
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.
• Ondansetron
Ondansetron is 5HT3 Receptor antagonist used to treat and prevent chemotherapy induced nausea and vomiting
• Metoclopramide
Dopamine receptor antagonist , acts at CTZ. Rescue medication, injection metoclopramide 0.5 mg/kg body weight/day.

Locations

Country	Name	City	State
India	Irch, Aiims , New Delhi , India	New Delhi	DEL

Sponsors (1)

Lead Sponsor	Collaborator
Dr Atul Sharma

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with complete response during the acute phase of AML remission induction chemotherapy		Up to day 8 of induction
Secondary	Time to first episode of vomiting		Up to day 13
Secondary	Incidence of delayed vomiting		From day 9 to day 13
Secondary	Severity of vomiting	Severity will be assessed by NCI CTCAE Criteria version 4.0	Up to day 13
Secondary	Incidence of requirement of rescue medication		Up to day 8