Acute Myelogenous Leukemia, Chemotherapy-induced Nausea and Vomiting
Conditions
Keywords
Nausea, Vomiting, CINV, Leukemia, High-risk Myelodysplastic syndrome, AML, Hematologic malignancies, Hematologic Disorder, Continuous multi-day chemotherapy, High-dose cytarabine, Palonosetron, Aloxi, Ondansetron, Zofran
Brief summary
The goal of this clinical research study is to compare the effectiveness of 3 drug schedules in preventing chemotherapy-related nausea and/or vomiting in patients with acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (MDS).
Detailed description
Chemotherapy-related nausea and vomiting is a frequent problem among patients with leukemia that can lead to further medical problems, such as malnutrition, dehydration, electrolyte imbalance, and a lower quality of life. Cytarabine, one of the drugs that is used to treat AML and high-risk MDS, is known to cause nausea and/or vomiting, so all patients that receive chemotherapy with cytarabine also need to receive medication to prevent these side effects. One standard-of-care drug to treat chemotherapy-related nausea and vomiting is called Ondansetron. Palonosetron is a new drug similar to Ondansetron that is designed to stay longer in the bloodstream. Researchers want to find out if palonosetron can prevent nausea and vomiting better than ondansetron. Women who are able to have children must have a negative blood or urine pregnancy test before starting treatment. If you are still eligible to take part in this study, you will be randomly assigned (as in the roll of the dice) to one of 3 treatment groups. Participants in the first group will be given Ondansetron as an intravenous (IV--through a needle in your vein) continuous infusion, from 30 minutes before your chemotherapy treatment until 12 hours after chemotherapy ends. This is considered the standard of care. Participants assigned to the second treatment group will be given palonosetron once a day by IV injection for 5 days. Each dose will be given over a period of 30 seconds, 30 minutes before your chemotherapy treatment. Participants assigned to the third treatment group will be given palonosetron once a day by IV injection, on Days 1, 3, and 5 of chemotherapy treatment. Each dose will be given over a period of 30 seconds, 30 minutes before your chemotherapy treatment. No matter what group you are assigned to, you will receive extra medication for nausea and/or vomiting as needed. You will be asked to fill out a study diary daily for 7 days, and it should take you no longer than 10 minutes to complete. The diary will be used to record the number of episodes of nausea and/or vomiting you experience during this study, as well as to record any need for extra medications, and to help researchers learn which of the 2 drugs helps the best to improve participants' quality of life (such as sleep, daily activities, and your ability to think and reason). You will be taken off study if intolerable side effects occur. This is an investigational study. The Food and Drug Administration (FDA) has approved palonosetron and Ondansetron for the prevention of chemotherapy-related nausea and vomiting, and both drugs are commercially available. Up to 150 participants will take part in this study. All will be enrolled at UT MD Anderson Cancer Center.
Interventions
DRUGOndansetron
8 mg IV as bolus followed by 24 mg IV from 30 minutes before chemotherapy until 12 hours after chemotherapy ends.
DRUGPalonosetron
Palonosetron Group 1: 0.25 mg IV bolus over 30 seconds daily for 5 days, 30 minutes before cytarabine chemotherapy. Palonosetron Group 2: 0.25 mg IV bolus over 30 seconds on Days 1, 3, and 5 of cytarabine chemotherapy, 30 minutes before chemotherapy.
Sponsors
Eisai Inc.
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients \> 18 years with acute myelogenous leukemia or high-risk myelodysplastic syndrome undergoing chemotherapy with high dose cytarabine (1.5 or 2gm/m\^2) containing regimens. 2. 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 nausea (oral intake is significantly decreased) or 3 nausea (no significant intake requiring intravenous fluids)\</= 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 other selective 5-HT3 receptor antagonists.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Complete Response | 7 days, starting first day of chemotherapy | Number of emesis (vomiting) episodes and no use of rescue medication during the administration of chemotherapy assessed as complete response. Complete response is defined as \< or equal to 1 episode of emesis during entire 7-day study period, no use of of rescue medication during the study period, and no more than moderate nausea (Grade 2, National Cancer Institutes (NCI) Common Terminology Criteria (CTC)) during chemotherapy. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: 9/13/2005 to 9/22/2009. All patients registered at The University of Texas M.D. Anderson Cancer Center.
Pre-assignment details
Of the 150 enrolled, only 143 patients were evaluable. Two patients were transferred to intensive care unit, two patients did not receive chemotherapy. One patient received one dose and was placed on hold. One patient received two antiemetic drugs; and 1 patient had a severe headache after two doses and was withdrawn.
Participants by arm
| Arm | Count |
|---|---|
| Ondansetron: Standard of Care Standard of care, Ondansetron 8 mg intravenous (IV) as bolus followed by 24 mg IV from 30 minutes before chemotherapy until 12 hours after chemotherapy ends. | 49 |
| Palonosetron Group 1 (5 Days) Palonosetron once a day 0.25 mg IV injection for 5 days, given over 30 seconds, 30 minutes before chemotherapy. | 51 |
| Palonosetron Group 2 (3 Days) Palonosetron once a day 0.25 mg IV injection on Days 1, 3, and 5 of chemotherapy, given over 30 seconds, 30 minutes before chemotherapy. | 50 |
| Total | 150 |
Baseline characteristics
| Characteristic | Ondansetron: Standard of Care | Palonosetron Group 1 (5 Days) | Palonosetron Group 2 (3 Days) | Total |
|---|---|---|---|---|
| Age Continuous | 54 years | 52 years | 53 years | 53 years |
| Region of Enrollment United States | 49 participants | 51 participants | 50 participants | 150 participants |
| Sex: Female, Male Female | 25 Participants | 25 Participants | 21 Participants | 71 Participants |
| Sex: Female, Male Male | 24 Participants | 26 Participants | 29 Participants | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 49 | 9 / 51 | 11 / 50 |
| serious Total, serious adverse events | 6 / 49 | 2 / 51 | 4 / 50 |
Outcome results
Primary
Number of Patients With Complete Response
Number of emesis (vomiting) episodes and no use of rescue medication during the administration of chemotherapy assessed as complete response. Complete response is defined as \< or equal to 1 episode of emesis during entire 7-day study period, no use of of rescue medication during the study period, and no more than moderate nausea (Grade 2, National Cancer Institutes (NCI) Common Terminology Criteria (CTC)) during chemotherapy.
Time frame: 7 days, starting first day of chemotherapy
Population: Analysis was per protocol. Seven patients were excluded from the efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ondansetron: Standard of Care | Number of Patients With Complete Response | 11 participants |
| Palonosetron Group 1 (5 Days) | Number of Patients With Complete Response | 15 participants |
| Palonosetron Group 2 (3 Days) | Number of Patients With Complete Response | 18 participants |