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

Phase 2

Completed

Brief Summary: 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: 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

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Palonosetron	ondansetron	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
Palonosetron	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
Palonosetron	Dexamethasone	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

Primary Outcome Measures

Name	Time	Method
Complete Response Rate for Delayed Chemotherapy Induced Nausea & Vomiting	120 hours	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.

Secondary Outcome Measures

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