Aprepitant as Antiemetic Prophylaxis in Patients With Acute Myeloid Leukemia Undergoing Induction Chemotherapy

A Phase II Open Label Study of Aprepitant as Antiemetic Prophylaxis in Patients With Acute Myeloid Leukemia Undergoing Induction Chemotherapy

Chemotherapy induced nausea and vomiting (CINV) is a major adverse effect of chemotherapy. This study is determining the incidence of vomiting/retching of the standard induction chemotherapy regimen for patients with acute myeloid leukemia (AML) who are also receiving an antiemetic known as aprepitant.

The standard frontline chemotherapy for patients with AML consists of cytarabine given as a 7 day continuous infusion plus 3 days of an anthracycline, most commonly daunorubicin, on days 1-3. This is known as the 3+7 regimen. Antiemetic treatments are usually given to patients for nausea and vomiting. Granisetron (a 5-HT3 receptor antagonist) is used on the 3 daunorubicin days and other antiemetics can be used for breakthrough nausea/vomiting.

This study will test that the prophylactic use of aprepitant, in addition to the standard antiemetic regimen used at Princess Margaret Hospital (PMH), will reduce the incidence of delayed onset vomiting/retching by Day 5 in AML patients receiving the standard 3+7 regimen, compared to retrospective data using this regimen.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Aprepitant

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Acute myeloid leukemia (AML), any subtype including acute promyelocytic leukemia (APL). Patients with either de novo or secondary AML are eligible.
• No prior AML induction chemotherapy.
• Due to receive standard 3+7 induction chemotherapy using daunorubicin on Days 1-3, plus cytarabine continuous infusion daily on Days 1-7.
• Age 18 and over.
• Serum bilirubin < or = 1.5 times the upper limit of normal (ULN).
• Serum aspartate aminotransferase and alanine aminotransferase < or = 2.5 times the ULN.
• Serum creatinine < 200 umol/L

Exclusion Criteria:

• Uncontrolled nausea or vomiting within 48 hours prior to start of induction therapy. Grade 0-1 nausea is permitted at the start of induction.
• Known hypersensitivity to granisetron or aprepitant.
• Patients currently receiving treatment with strong CYP3A4 inhibitors or substrates and treatment cannot be either discontinued or switched to a different medication prior to starting study drug.
• Not able to swallow or absorb oral medications.
• Documented active central nervous system (CNS) leukemia or recent CNS hemorrhage.

• Concomitant use of:

  1. Other investigational agents during induction therapy
  2. Radiotherapy during, or one month prior to, induction therapy
  3. Systemic corticosteroids
  4. Other chemotherapy agents on Days 1-8
• Pregnant or breast feeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Aprepitant	Drug: Aprepitant; Oral aprepitant will be given to the participant on Days 1-5 of standard induction treatment. A dose of 125 mg will be given on Day 1 and 80 mg will be given on Days 2-5.; Other Names: Emend

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Incidence of Vomiting/Retching From Day 1 Through End of Day 5	Cumulative incidence will be determined by the patient self-assessment form, supplemented by the nursing inpatient records.	Day 1 through end of Day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of Nausea Per Day, on Days 1-8.		Days 1 to 8
Daily Number of Vomiting or Retching Incidents From Days 1-8	This will be determined by both self-assessment form which will be filled out by the patient on a daily basis, and review of the nursing inpatient records.	Days 1 to 8
Percentage of Participants Experiencing Vomiting or Retching From Days 1-8.	This will be determined by both self-assessment form which will be filled out by the patient on a daily basis, and review of the nursing inpatient records.	Days 1 to 8
Percentage of Patients Experiencing Nausea From Days 1-8.		Days 1 to 8
Percentage of Patients' Use of Supplemental Anti-emetics as Determined by the Total Number of Doses Per Day and in Total, From Days 1-8.		Days 1 to 8
To Evaluate the Tolerance of Aprepitant by Documenting All Toxicities on Days 1-8 and All Unexpected Serious Adverse Events up to Day 30.		Days 1 to 8
Severity of Nausea Per Day, on Days 1-8.		Days 1 to 8

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Joseph M Brandwein, MD, FRCPC, University Health Network - Princess Margaret Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (ACTUAL): August 1, 2013
• Study Completion (ACTUAL): August 30, 2013

Study Registration Dates

• First Submitted: March 25, 2011
• First Submitted That Met QC Criteria: April 11, 2011
• First Posted (ESTIMATE): April 12, 2011

Study Record Updates

• Last Update Posted (ACTUAL): November 22, 2021
• Last Update Submitted That Met QC Criteria: November 18, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: AML
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Neurokinin-1 Receptor Antagonists; Aprepitant
• Other Study ID Numbers: AML-11-001