Clinical trial NCT01334086: Aprepitant as Antiemetic Prophylaxis in Patients With Acute Myeloid Leukemia Undergoing Induction Chemotherapy
Official title: A Phase II Open Label Study of Aprepitant as Antiemetic Prophylaxis in Patients With Acute Myeloid Leukemia Undergoing Induction Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Keywords: AML
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2011-04-12
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Percentage of Participants With Incidence of Vomiting/Retching From Day 1 Through End of Day 5
timeFrame: Day 1 through end of Day 5
Secondary outcomes:
measure: Presence of Nausea Per Day, on Days 1-8.
timeFrame: Days 1 to 8
measure: Daily Number of Vomiting or Retching Incidents From Days 1-8
timeFrame: Days 1 to 8
measure: Percentage of Participants Experiencing Vomiting or Retching From Days 1-8.
timeFrame: Days 1 to 8
measure: Percentage of Patients Experiencing Nausea From Days 1-8.
timeFrame: Days 1 to 8
measure: 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.
timeFrame: Days 1 to 8
measure: To Evaluate the Tolerance of Aprepitant by Documenting All Toxicities on Days 1-8 and All Unexpected Serious Adverse Events up to Day 30.
timeFrame: Days 1 to 8
measure: Severity of Nausea Per Day, on Days 1-8.
timeFrame: Days 1 to 8
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: University Health Network - Princess Margaret Hospital
name: Joseph M Brandwein, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References: