Acute Myeloid Leukemia
Conditions
Keywords
AML
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.
Interventions
DRUGAprepitant
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.
Sponsors
Merck Sharp & Dohme LLC
University Health Network, Toronto
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Incidence of Vomiting/Retching From Day 1 Through End of Day 5 | Day 1 through end of Day 5 | Cumulative incidence will be determined by the patient self-assessment form, supplemented by the nursing inpatient records. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Daily Number of Vomiting or Retching Incidents From Days 1-8 | Days 1 to 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. |
| Percentage of Participants Experiencing Vomiting or Retching From Days 1-8. | Days 1 to 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. |
| Percentage of Patients Experiencing Nausea From Days 1-8. | Days 1 to 8 | — |
| Presence of Nausea Per Day, on 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 | — |
| 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 | — |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aprepitant 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. | 41 |
| Total | 41 |
Baseline characteristics
| Characteristic | Aprepitant |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 15 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants |
| Age, Continuous | 56 years |
| Region of Enrollment Canada | 41 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 40 / 41 |
| serious Total, serious adverse events | 2 / 41 |
Outcome results
Primary
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.
Time frame: Day 1 through end of Day 5
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant | Percentage of Participants With Incidence of Vomiting/Retching From Day 1 Through End of Day 5 | 26.3 percentage of particpants |
Secondary
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.
Time frame: Days 1 to 8
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aprepitant | Daily Number of Vomiting or Retching Incidents From Days 1-8 | Day 1 | 7 incidents |
| Aprepitant | Daily Number of Vomiting or Retching Incidents From Days 1-8 | Day 2 | 11 incidents |
| Aprepitant | Daily Number of Vomiting or Retching Incidents From Days 1-8 | Day 3 | 16 incidents |
| Aprepitant | Daily Number of Vomiting or Retching Incidents From Days 1-8 | Day 4 | 13 incidents |
| Aprepitant | Daily Number of Vomiting or Retching Incidents From Days 1-8 | Day 5 | 13 incidents |
| Aprepitant | Daily Number of Vomiting or Retching Incidents From Days 1-8 | Day 6 | 24 incidents |
| Aprepitant | Daily Number of Vomiting or Retching Incidents From Days 1-8 | Day 7 | 13 incidents |
| Aprepitant | Daily Number of Vomiting or Retching Incidents From Days 1-8 | Day 8 | 11 incidents |
Secondary
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.
Time frame: Days 1 to 8
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant | Percentage of Participants Experiencing Vomiting or Retching From Days 1-8. | 34.2 percentage of particpants |
Secondary
Percentage of Patients Experiencing Nausea From Days 1-8.
Time frame: Days 1 to 8
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant | Percentage of Patients Experiencing Nausea From Days 1-8. | 68.4 percentage of particpants |
Secondary
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.
Time frame: Days 1 to 8
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aprepitant | 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. | Day 1 | 18 % of pts receiving breakthrough |
| Aprepitant | 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. | Day 2 | 29 % of pts receiving breakthrough |
| Aprepitant | 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. | Day 3 | 39 % of pts receiving breakthrough |
| Aprepitant | 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. | Day 4 | 58 % of pts receiving breakthrough |
| Aprepitant | 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. | Day 5 | 65 % of pts receiving breakthrough |
| Aprepitant | 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. | Day 6 | 75 % of pts receiving breakthrough |
| Aprepitant | 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. | Day 7 | 68 % of pts receiving breakthrough |
| Aprepitant | 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. | Day 8 | 53 % of pts receiving breakthrough |
Secondary
Presence of Nausea Per Day, on Days 1-8.
Time frame: Days 1 to 8
Secondary
Severity of Nausea Per Day, on Days 1-8.
Time frame: Days 1 to 8
Secondary
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: Days 1 to 8