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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by University Health Network, Toronto
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT01334086
First received: March 25, 2011
Last updated: January 10, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Acute Myeloid Leukemia
Drug: Aprepitant
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase II Open Label Study of Aprepitant as Antiemetic Prophylaxis in Patients With Acute Myeloid Leukemia Undergoing Induction Chemotherapy

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Cumulative incidence of vomiting/retching from Day 1 through end of Day 5. [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Presence of nausea per day, on Days 1-8. [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Number of episodes of vomiting or retching per day, on Days 1-8. [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Cumulative incidence of vomiting or retching from Days 1-8. [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Cumulative incidence of nausea from Days 1-8. [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Patients' use of supplemental anti-emetics as determined by the total number of doses per day and in total, from Days 1-8. [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • To evaluate the tolerance of aprepitant by documenting all toxicities on Days 1-8 and all unexpected serious adverse events up to Day 30. [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
  • Severity of nausea per day, on Days 1-8. [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 82
Study Start Date: September 2011
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Emend

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01334086

Contacts
Contact: Joseph M Brandwein, MD, FRCPC 416-946-4501 ext 2824 joseph.brandwein@uhn.on.ca

Locations
Canada, Ontario
Princess Margaret Hospital Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Lorraine Whitehead, RN    416-946-4501 ext 4491    lorraine.whitehead@uhn.ca   
Principal Investigator: Joseph M Brandwein, MD, FRCPC         
Sponsors and Collaborators
University Health Network, Toronto
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Joseph M Brandwein, MD, FRCPC University Health Network - Princess Margaret Hospital
  More Information

No publications provided

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT01334086     History of Changes
Other Study ID Numbers: AML-11-001
Study First Received: March 25, 2011
Last Updated: January 10, 2013
Health Authority: Canada: Health Canada
Canada: Ethics Review Committee

Keywords provided by University Health Network, Toronto:
AML

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Antiemetics
Aprepitant
Fosaprepitant
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Gastrointestinal Agents
Neurokinin-1 Receptor Antagonists
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 21, 2014