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

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

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.

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.

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