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

Study Overview
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Brief Summary
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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.

Detailed Description
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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

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

Conditions
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Chemotherapy-induced Nausea and Vomiting

Intervention / Treatment
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* Drug: Palonosetron
* Drug: ondansetron
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Palonosetron<br>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<br>* 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<br>* Other names: Aloxi;Drug: ondansetron<br>* Prior to IV chemotherapy - ondansetron 8mg IV & Dexamethasone 10 mg IV On the last day of chemotherapy - Palonosetron .25 mg IV, dexamethasone 10mg IV<br>* Other names: zofran;Drug: Dexamethasone<br>* Prior to IV chemotherapy - ondansetron 8mg IV & Dexamethasone 10 mg IV On the last day of chemotherapy - Palonosetron .25 mg IV, dexamethasone 10mg IV<br>* Other names: Dex;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autologous stem cell transplant, BEAM, Oral busulfan, Cyclophosphamide, Etoposide, Carboplatin, melphalan