Palonosetron, Ondansetron, and Dexamethasone for Delayed Nausea and Vomiting in Autologous Transplant Patients

A Unique Schedule of Palonosetron, Ondansetron, and Dexamethasone for the Prevention of Delayed Nausea and Vomiting in Patients Receiving Moderately Emetogenic Myeloablative Chemotherapy

In this study, patients will receive ondansetron 8mg and dexamethasone 10mg intravenously 30 minutes prior to myeloablative preparative chemotherapy until the last day of chemotherapy. On the final day of chemotherapy, palonosetron 0.25mg and dexamethasone 10mg will be administered intravenously 30 minutes prior to the chemotherapy. If the chemotherapy regimen is only 1 day of the chemotherapy then only palonosetron and dexamethasone will be administered 30 minutes prior to chemotherapy. Dexamethasone 8mg once daily will be given orally for 2 days following chemotherapy.

Study Overview

• Status: Completed
• Conditions: Chemotherapy-induced Nausea and Vomiting
• Intervention / Treatment: Drug: Palonosetron; Drug: ondansetron; Drug: Dexamethasone

Detailed Description

In order to decrease this delayed CINV, the investigators have developed a unique schedule of antiemetics that takes advantage of palonosetron's long elimination half-life (40 hours). In this study, patients will receive ondansetron 8mg and dexamethasone 10mg intravenously 30 minutes prior to myeloablative preparative chemotherapy until the last day of chemotherapy. On the final day of chemotherapy, palonosetron 0.25mg and dexamethasone 10mg will be administered intravenously 30 minutes prior to the chemotherapy. If the chemotherapy regimen is only 1 day of the chemotherapy then only palonosetron and dexamethasone will be administered 30 minutes prior to chemotherapy. Dexamethasone 8mg once daily will be given orally for 2 days following chemotherapy. The investigators hypothesize that this antiemetic schedule will significantly reduce the delayed CINV compared to historical controls

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• candidate for high-dose chemotherapy and autologous hematopoietic stem cell transplantation
• Karnofsky performance status >/= 60%
• scheduled to receive one of the following conditioning regimens
• BEAM
• Oral Busulfan/cyclophosphamide with or without etoposide
• Carboplatin/Etoposide
• Melphalan
• Negative pregnancy test
• Must be able to complete a daily nausea/vomiting questionnaire and Quality of Life

Exclusion Criteria:

• Active infection requiring IV antibiotics
• Known active hepatitis B and/or hepatitis C or HIV infection
• prior non-hematological malignancies at other sites except surgically treated non-melanoma skin cancer, superficial cervical cancer or other cancer from which the patient had been disease free for >/= 5 years
• Uncontrolled medical problems including any of the following
• Diabetes mellitus
• Cardiac, pulmonary, hepatic or renal disease
• myocardial infarction within the past 6 months
• Morbid obesity (BMT >40)
• History of CNS metastases, psychiatric or CNS disorders interfering with the ability to comply with the study
• Known hypersensitivity to 5-HT3 antagonists, dexamethasone and/or their components
• Intrathecal therapy within 24 hours before starting preparative regimen
• Receiving any antiemetic therapy 24 hours before starting preparative regimen
• Any 5-HT3 antagonist used as a rescue medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Palonosetron; All patients will receive the following medications prior to and during their high dose chemotherapy for autologous stem cell transplantation Prior to IV chemotherapy - ondansetron 8mg IV & Dexamethasone 10 mg IV on the last day of chemotherapy - Palonosetron .25 mg IV, dexamethasone 10mg IV Day 1-2 after IV chemotherapy - Dexamethasone 8 mg PO

Drug: Palonosetron; Prior to IV chemotherapy - ondansetron 8mg IV & Dexamethasone 10 mg IV On the last day of chemotherapy - Palonosetron .25 mg IV, dexamethasone 10mg IV Day 1-2 after IV chemotherapy - Dexamethasone 8 mg PO; Other Names: Aloxi; Drug: ondansetron; Prior to IV chemotherapy - ondansetron 8mg IV & Dexamethasone 10 mg IV On the last day of chemotherapy - Palonosetron .25 mg IV, dexamethasone 10mg IV; Other Names: zofran; Drug: Dexamethasone; Prior to IV chemotherapy - ondansetron 8mg IV & Dexamethasone 10 mg IV On the last day of chemotherapy - Palonosetron .25 mg IV, dexamethasone 10mg IV; Other Names: Dex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response Rate for Delayed Chemotherapy Induced Nausea & Vomiting	Proportion of patients achieving a delayed CINV complete response (CR) defined as no emetic episode and no use of rescue medications during the 24-120 hour period post chemotherapy.	120 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Remission During Acute Phase Post-chemotherapy	Proportion of patients achieving an acute CINV CR during the acute phase post -chemotherapy (0-24 hours)	24 hours
Complete Remission During Overall Chemotherapy Time Period	Proportion of patients achieving a CR during the cumulative overall 0-120 hour time period	120 hours
Complete Control Rate for Nausea & Vomiting	Complete control rate (CC; defined as no emetic episodes, no rescue medication use, and no more than mild nausea)	120 hours
Emetic Episodes	Number of emetic episodes	120 Hours
Patients Who Experience First Emetic Episode Within 24 Hours	Number of patients with first emetic episode experienced within 24 hours	24 hours
Number of Patients That Required First Administration of Rescue Medication Within 24 Hours	Number of patients who required the use of rescue medication (lorazepam, prochlorperazine, promethazine, metoclopramide, scopolamine, or dronabinol) within the first 24 hours	24 hours
Number of Patients That Experience Treatment Failure Within the First 24 Hours	Number of patients with first emetic episode or time to administration of rescue therapy, whichever occurred first, within the first 24 hours	24 hours

Collaborators and Investigators

• Sponsor: Northside Hospital, Inc.
• Collaborators: Blood and Marrow Transplant Group of Georgia
• Investigators: Principal Investigator: Scott R Solomon, MD, Blood and Marrow Transplant Group of Georgia

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: June 8, 2011
• First Submitted That Met QC Criteria: June 8, 2011
• First Posted (Estimate): June 9, 2011

Study Record Updates

• Last Update Posted (Actual): April 17, 2017
• Last Update Submitted That Met QC Criteria: March 16, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Cyclophosphamide; Carboplatin; Etoposide; melphalan; Autologous stem cell transplant; BEAM; Oral busulfan
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Nausea; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; Anti-Anxiety Agents; Serotonin 5-HT3 Receptor Antagonists; Antipruritics; Dexamethasone; Palonosetron; Ondansetron
• Other Study ID Numbers: NSH 940

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No