Palonosetron Versus Ondansetron for the Prevention of Nausea and Vomiting

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase II, Open, Randomized Comparative Trial of Two Different Schedules of Palonosetron Versus Ondansetron for the Prevention of Nausea and Vomiting in Patients With Hematologic Malignancies Receiving Regimens Containing High-dose Cytarabine

Conditions
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Acute Myelogenous Leukemia, Chemotherapy-induced Nausea and Vomiting

Intervention / Treatment
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* Drug: Ondansetron
* Drug: Palonosetron


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. 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: 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. Patients with ongoing emesis due to any organic etiology. Patients with known hypersensitivity to the study drug or to other selective 5-HT3 receptor antagonists.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ondansetron: Standard of Care<br>Standard of care, Ondansetron 8 mg IV as bolus followed by 24 mg IV from 30 minutes before chemotherapy until 12 hours after chemotherapy ends. | Drug: Ondansetron<br>* 8 mg IV as bolus followed by 24 mg IV from 30 minutes before chemotherapy until 12 hours after chemotherapy ends.<br>* Other names: Zofran;|
| Experimental: Palonosetron Group 1 (5 Days)<br>Palonosetron once a day 0.25 mg IV injection for 5 days, given over 30 seconds, 30 minutes before chemotherapy treatment. | Drug: Palonosetron<br>* 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.<br>* Other names: Aloxi;|
| Experimental: Palonosetron Group 2 (3 Days)<br>Palonosetron once a day 0.25 mg IV injection on Days 1, 3, and 5 of chemotherapy treatment, given over 30 seconds, 30 minutes before chemotherapy treatment. | Drug: Palonosetron<br>* 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.<br>* Other names: Aloxi;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 7 days, starting first day of chemotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nausea, Vomiting, CINV, Leukemia, High-risk Myelodysplastic syndrome, AML, Hematologic malignancies, Hematologic Disorder, Continuous multi-day chemotherapy, High-dose cytarabine, Palonosetron, Aloxi, Ondansetron, Zofran