Ondansetron Versus Aprepitant Plus Ondansetron for Emesis

Comparative Trial Ondansetron Alone Versus Combination of Ondansetron Plus Aprepitant for Prevention of Nausea and Vomiting With Hematologic Malignancies Receiving Regimens Containing High-dose Cytarabine

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.

Study Overview

• Status: Completed
• Conditions: Hematologic Diseases; Myelodysplastic Syndrome; Acute Myelogenous Leukemia; Chronic Myelogenous Leukemia
• Intervention / Treatment: Drug: Ondansetron; Drug: Aprepitant

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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.	Drug: 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.; Other Names: Zofran
ACTIVE_COMPARATOR: 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.	Drug: 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.; Other Names: Zofran; Drug: 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.; Other Names: Emend; L 754030; MK 869

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	First 6 treatment days
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.	First 6 treatment days

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• University of Texas MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (ACTUAL): April 1, 2013
• Study Completion (ACTUAL): May 1, 2015

Study Registration Dates

• First Submitted: August 6, 2009
• First Submitted That Met QC Criteria: August 6, 2009
• First Posted (ESTIMATE): August 7, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): June 25, 2015
• Last Update Submitted That Met QC Criteria: May 28, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Nausea; Vomiting; AML; Ondansetron; CML; Acute myelogenous leukemia; Chronic Myelogenous Leukemia; Aprepitant; Emend; Zofran; Hematologic Disorder; Emesis; HR-MDS; High-risk myelodysplastic syndrome; L 754030; MK 869
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Myeloproliferative Disorders; Precancerous Conditions; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Hematologic Diseases; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; Anti-Anxiety Agents; Antipruritics; Neurokinin-1 Receptor Antagonists; Ondansetron; Aprepitant
• Other Study ID Numbers: 2008-0615; NCI-2009-01517 (REGISTRY: NCI CTRP)