Palonosetron Plus Aprepitant Versus Palonosetron in Preventing Nausea and Vomiting in Leukemic Patients

Study Overview
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Brief Summary
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The aim of present study is to evaluate if the addition of Aprepitant to multiple doses of palonosetron IV enhances the efficacy of multiple doses of palonosetron IV alone, in preventing CINV in AML or High risk MDS patient, treated with multiple days chemotherapy.

Detailed Description
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This is an open-label, randomized, comparative, multicenter phase II study in patients with AML scheduled to receive multiple days chemotherapy. Patients will receive either PALO+APR or the PALO regimen in a 1:1 ratio according to a computer-generated, random allocation schedule. Below are described the details for both antiemetic regimens: PALO+APR regimen: oral aprepitant will be given on days 1-3 (day 1, 125 mg, days 2-3, 80 mg 1 hour before chemotherapy ) and multiple intravenous bolus of Palonosetron without dexamethasone, prior to the administration of chemotherapy, starting the first day of treatment. PALO regimen: multiple intravenous bolus of Palonosetron without dexamethasone, prior to the administration of chemotherapy, starting the first day of treatment.

Official Title
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Phase II Randomized Study of Multiple Doses of Palonosetron Plus Aprepitant Versus Multiple Doses of Palonosetron Alone in Preventing CINV in Patients With Newly Diagnosed AML or High-risk MDS Receiving Multiple Days Chemotherapy

Conditions
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Chemotherapy Induced Nausea and Vomiting

Intervention / Treatment
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* Drug: Palonosetron + Aprepitant
* Drug: Palonosetron


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Acute Myeloid Leukaemia or High-risk MDS according to IPSS Patient eligible for AML-like induction therapy Candidate for multiple-days chemotherapy (minimum 3 days) Age more, equal18 years ECOG 0-2 Not pregnant or nursing Must be able to complete the patient's diary Provide written informed consent Exclusion Criteria: AML or HR-MDS therapy-related Active infection requiring intravenous antibiotics Prior malignancies at other sites except surgically treated non-melanoma skin cancer, prostate cancer, superficial cervical cancer, or other cancer from which the patient had been disease-free for more/equal 5 years Unacceptable hepatic function (more of 2 times the upper limit of normal for liver transaminases) and renal function (creatinine more of 1.5 times the upper limit of normal) unless disease-related Myocardial infarction within the past 6 months Psychiatric or CNS disorders interfering with ability to comply with study protocol Known hypersensitivity to 5-HT3 antagonists and their components CSF involvement Pre-existing nausea or vomiting

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 |
| --- | --- |
| Experimental: Palonosetron + Aprepitant<br>Oral aprepitant will be given on days 1-3 (day 1, 125 mg 1 h before chemohterapy; days 2-3, 80 mg) multiple intravenous bolus of palonosetron 0.25 mg, 30 minutes before chemotherapy, every other single days, for a minimum of 2 administration (day 1, 3), in case of a 3 days chemotherapy regimen, and a maximum of 5 doses (day 1,3,5,7, 9) in case of a 10 days chemotherapy. | Drug: Palonosetron + Aprepitant<br>* Aloxi 0.25mg Emend 125/80/80 mg<br>* Other names: Aloxi + Emend;|
| Active Comparator: Palonosetron<br>multiple intravenous bolus of palonosetron 0.25 mg, 30 minutes before chemotherapy, every other single days, for a minimum of 2 administration (day 1, 3), in case of a 3 days chemotherapy regimen, and a maximum of 5 doses (day 1,3,5,7, 9) in case of a 10 days chemotherapy. | Drug: Palonosetron<br>* Aloxi 0.25mg<br>* Other names: Aloxi;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response | The primary endpoint is the overall rate of patients achieving a complete response (defined as no emetic episode and no use of rescue medication) during the overall phase. | 5 days after chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Control | No emetic episode, no need for rescue medication, with a maximum grade of mild nausea | 5 days after chemotherapy | 
| Emesis-free | Percentage of patients without emetic episodes | 5 days after chemotherapy | 
| Presence of nausea | Presence of nausea graded according to Likert scale (none, mild, moderate and severe) | 5 days after chemotherapy | 
| Treatment failure | Time (days) to treatment failure (first emetic episode or first need of rescue medication, whichever occurs first) | 5 days after chemotherapy | 
| Patient global satisfaction | Patient global satisfaction with antiemetic therapy, as measured by a visual analogue scale (VAS) | 5 days after chemotherapy | 
| Safety and tolerability | Number of patients experienced at least one adverse events related to study drug administration. | 5 days after chemotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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palonosetron, aprepitant, CINV, AML, multiple-days