Acute Myelogenous Leukemia, Chronic Myelogenous Leukemia, Hematologic Diseases, Myelodysplastic Syndrome
Conditions
Keywords
Hematologic Disorder, Acute myelogenous leukemia, AML, High-risk myelodysplastic syndrome, HR-MDS, Chronic Myelogenous Leukemia, CML, Ondansetron, Zofran, Aprepitant, Emend, L 754030, MK 869, Emesis, Nausea, Vomiting
Brief summary
The goal of this clinical research study is to compare the effectiveness of receiving a combination of ondansetron and aprepitant to receiving ondansetron alone in helping to prevent nausea and/or vomiting in patients with Acute myeloid leukemia (AML) or high-risk (HR) Myelodysplastic syndromes (MDS) who are receiving cytarabine. The safety of this drug combination will also be studied.
Detailed description
Cytarabine is a drug that is used to treat AML and high-risk MDS. It is known to cause nausea and/or vomiting. All patients that receive cytarabine also receive drugs to help prevent these side effects. The Study Drugs: Ondansetron is designed to block the action of serotonin, a substance in the brain that causes chemotherapy-related nausea and vomiting. Aprepitant is designed to block a different natural substance in the brain that causes chemotherapy-related nausea and vomiting. Study Groups: If you are found eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 groups. You will have an equal chance of being in either group. If you are in Group 1, you will receive ondansetron. If you are in Group 2, you will receive ondansetron and aprepitant. Study Drug Administration: Both groups will receive ondansetron by vein from 30 minutes before receiving chemotherapy until 6 to12 hours after chemotherapy. The length of the chemotherapy infusion will be different for all patients. If you are in Group 2, in addition to ondansetron, you will take 1 capsule of aprepitant every morning while receiving chemotherapy. You will take your last dose of aprepitant the day after your chemotherapy infusion is completed. If you miss a dose of aprepitant, you can take it as soon as you remember. Study Diary: You will fill out a study diary every day for the 7 days after the chemotherapy. You will record how often you experience nausea and/or vomiting and any time you need other medications during this study. It should take about 5 minutes to complete each time. Length of Study: You will be on study for up to 7 days. You will be taken off study if intolerable side effects occur. Blood Draws: Blood (about 1 teaspoon) will be drawn for routine tests after your last dose (+/- 3 days) of study drug. This is an investigational study. Ondansetron and aprepitant are both FDA approved and commercially available for the prevention of chemotherapy-related nausea and vomiting. Using the drugs in combination is investigational. Up to 100 participants will take part in this study. All will be enrolled at MD Anderson.
Interventions
DRUGOndansetron
8 mg bolus by vein from 30 minutes before receiving chemotherapy followed by 24 mg by vein continuous infusion daily while receiving chemotherapy until 12 hours after chemotherapy.
DRUGAprepitant
125 mg capsule by mouth every morning while receiving chemotherapy followed by 80 mg capsule by mouth daily while receiving chemotherapy continued till 1 day after last chemotherapy dose.
Sponsors
Merck Sharp & Dohme LLC
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients greater than or equal to 18 years of age. 2. Patients with a diagnosis of acute myelogenous leukemia, high-risk myelodysplastic syndrome, chronic myelogenous leukemia in blast crisis or acute undifferentiated leukemia who will receive chemotherapy with regimens containing high-dose cytarabine (greater or equal 1g/m\^2/d for at least 3 days). 3. Patients must sign an informed consent indicating they are aware of the investigational nature of this study, in keeping with the policies of the hospital.
Exclusion criteria
1. Patients with emesis or grade 2 or 3 nausea present less than or equal to 24 hours before chemotherapy. 2. Patients with ongoing emesis due to any organic etiology 3. Patients with known hypersensitivity to the study drug or to 5-HT3 receptor antagonists 4. Patients receiving pimozide, terfenadine, astemizole, or cisapride
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participant Responses | First 6 treatment days | Participant response defined as: Complete response - no emetic episode, no nausea and no rescue medication during the administration of chemotherapy; Partial response - less than or equal to one episode of emesis in 24 hours, no rescue medication, and no more than moderate nausea (grade 2 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)) during chemotherapy. Vomit was defined as expulsion of stomach contents through the mouth, nausea as stomach distress with distaste for food and an urge to vomit, and rescue medication as antiemetic medications given to treat nausea and/or vomit that did not respond to the initial prophylactic regimen. Treatment success was defined as no nausea, no vomiting and no need for rescue medication within the first 6 treatment days with continuous monitoring. |
| Treatment Success Rate | First 6 treatment days | Treatment success is defined as no nausea, no vomiting and no need for rescue medication (or complete response) within the first 6 treatment days. Treatment success rate defined as percentage of participants achieving treatment success. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: 11/11/09 to 3/20/2013. All participants registered at The University of Texas M.D. Anderson Cancer Center.
Pre-assignment details
Of the 100 participants registered for screening on this study, fifty participants were randomized to Ondansetron alone (Group 1) and forty-eight participants to Ondansetron plus Aprepitant (Group 2).
Participants by arm
| Arm | Count |
|---|---|
| Group 1: Ondansetron Ondansetron 8 mg bolus by vein from 30 minutes before receiving chemotherapy followed by 24 mg by vein continuous infusion daily while receiving chemotherapy until 12 hours after chemotherapy. | 50 |
| Group 2: Ondansetron + Aprepitant Ondansetron 8 mg bolus by vein from 30 minutes before receiving chemotherapy followed by 24 mg by vein continuous infusion daily while receiving chemotherapy until 12 hours after chemotherapy. Aprepitant 125 mg capsule by mouth every morning while receiving chemotherapy followed by 80 mg capsule by mouth daily while receiving chemotherapy continued till 1 day after last chemotherapy dose. | 48 |
| Total | 98 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Ineligible | 2 | 2 |
| Overall Study | Insurance Denial | 2 | 2 |
| Overall Study | Physician Decision | 2 | 2 |
| Overall Study | Received treatment at home | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Group 1: Ondansetron | Group 2: Ondansetron + Aprepitant | Total |
|---|---|---|---|
| Age, Continuous | 56 years | 53 years | 55 years |
| Region of Enrollment United States | 50 participants | 48 participants | 98 participants |
| Sex: Female, Male Female | 21 Participants | 22 Participants | 43 Participants |
| Sex: Female, Male Male | 29 Participants | 26 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 43 / 46 | 41 / 44 |
| serious Total, serious adverse events | 3 / 46 | 3 / 44 |
Outcome results
Primary
Participant Responses
Participant response defined as: Complete response - no emetic episode, no nausea and no rescue medication during the administration of chemotherapy; Partial response - less than or equal to one episode of emesis in 24 hours, no rescue medication, and no more than moderate nausea (grade 2 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)) during chemotherapy. Vomit was defined as expulsion of stomach contents through the mouth, nausea as stomach distress with distaste for food and an urge to vomit, and rescue medication as antiemetic medications given to treat nausea and/or vomit that did not respond to the initial prophylactic regimen. Treatment success was defined as no nausea, no vomiting and no need for rescue medication within the first 6 treatment days with continuous monitoring.
Time frame: First 6 treatment days
Population: Of the 98 participants in the study, six (6) in Group 1: Ondansetron and nine (9) in Group 2: Ondansetron + Aprepitant were not.evaluable.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1: Ondansetron | Participant Responses | Partial Response | 9 participants |
| Group 1: Ondansetron | Participant Responses | Complete Response | 20 participants |
| Group 1: Ondansetron | Participant Responses | No Response | 13 participants |
| Group 2: Ondansetron + Aprepitant | Participant Responses | Complete Response | 21 participants |
| Group 2: Ondansetron + Aprepitant | Participant Responses | Partial Response | 12 participants |
| Group 2: Ondansetron + Aprepitant | Participant Responses | No Response | 8 participants |
Primary
Treatment Success Rate
Treatment success is defined as no nausea, no vomiting and no need for rescue medication (or complete response) within the first 6 treatment days. Treatment success rate defined as percentage of participants achieving treatment success.
Time frame: First 6 treatment days
Population: Of the 98 participants in the study, six (6) in Group 1: Ondansetron and nine (9) in Group 2: Ondansetron + Aprepitant were not.evaluable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: Ondansetron | Treatment Success Rate | 48 percentage of participants |
| Group 2: Ondansetron + Aprepitant | Treatment Success Rate | 51 percentage of participants |