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.

Study Overview

• Status: Unknown
• Conditions: Chemotherapy Induced Nausea and Vomiting
• Intervention / Treatment: Drug: Palonosetron + Aprepitant; Drug: Palonosetron

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 134
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Napoli, Italy, 80121
    • Recruiting
    • ARON " Cardarelli"
    • Contact: Felicetto Ferrara, MD; Email: felicettoferrara@katamail.com
    • Principal Investigator: Felicetto Ferrara, MD
  • BA
    • Bari, BA, Italy, 70124
      • Active, not recruiting
      • Università-Azienda Policlinico di Bari
  • BR
    • Brindisi, BR, Italy, 72010
      • Recruiting
      • Ospedale Perrino
      • Contact: Angela Melpignano, MD; Email: brinemat@tin.it
      • Principal Investigator: Angela Melpignano, MD
  • CZ
    • Catanzaro, CZ, Italy, 88100
      • Active, not recruiting
      • Ospedale Pugliese-Ciacco
  • FG
    • San Giovanni Rotondo, FG, Italy, 71013
      • Recruiting
      • IRCCS Casa Sollievo della Sofferenza
      • Contact: Nicola Cascavilla, MD; Email: nicola.cascavilla@tin.it
  • LE
    • Lecce, LE, Italy, 73100
      • Recruiting
      • Ospedale Vito Fazzi
      • Contact: Nicola Di Renzo, MD; Email: direnzo.ematolecce@libero.it
    • Tricase, LE, Italy, 73100
      • Recruiting
      • Ospedale "Cardinale Panico"
      • Principal Investigator: Vincenzo Pavone, MD
      • Contact: Vincenzo Pavore, MD; Email: salentoematologia@piafondazionepanico.it
  • ME
    • Messina, ME, Italy, 98121
      • Recruiting
      • A.O. Riuniti Papardo - Piemonte
      • Principal Investigator: Donato Mannina, MD
      • Contact: Donato Mannina, MD; Email: donadani@tiscali.it
  • PA
    • Palermo, PA, Italy, 90127
      • Recruiting
      • Casa di Cura "La Maddalena"
      • Contact: Maurizio Musso, MD; Email: mamusso@libero.it
    • Palermo, PA, Italy, 90127
      • Recruiting
      • Ospedale Ascoli Civico Palermo
      • Contact: Anxur Merenda, MD; Email: anxurmerenda@libero.it
      • Principal Investigator: Anxur Merenda, MD
  • TA
    • Taranto, TA, Italy, 74100
      • Recruiting
      • Ospedale Moscati
      • Contact: Patrizio Mazza, MD; Email: ematologia.taranto@libero.it
      • Principal Investigator: Patrizio Mazza, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Palonosetron + Aprepitant; 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; Aloxi 0.25mg Emend 125/80/80 mg; Other Names: Aloxi + Emend
Active Comparator: Palonosetron; 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; Aloxi 0.25mg; Other Names: Aloxi

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Associazione Salentina Angela Serra
• Investigators: Principal Investigator: Nicola Di Renzo, MD, Ospedale Vito Fazzi

Publications and helpful links

General Publications

• Di Renzo N, Melillo L, Porretto F, Dargenio M, Pavone V, Pastore D, Mazza P, Mannina D, Merenda A, Cascavilla N, Greco G, Matera R, Bonizzoni E, Celio L, Musso M. Every-other-day palonosetron plus aprepitant for prevention of emesis following induction chemotherapy for acute myeloid leukemia: A randomized, controlled study from the "Rete Ematologica Pugliese". Cancer Med. 2020 Jan;9(1):170-178. doi: 10.1002/cam4.2628. Epub 2019 Nov 14.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Anticipated): August 1, 2014
• Study Completion (Anticipated): October 1, 2014

Study Registration Dates

• First Submitted: July 17, 2014
• First Submitted That Met QC Criteria: July 30, 2014
• First Posted (Estimate): July 31, 2014

Study Record Updates

• Last Update Posted (Estimate): July 31, 2014
• Last Update Submitted That Met QC Criteria: July 30, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: AML; aprepitant; palonosetron; CINV; multiple-days
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Nausea; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Serotonin Agents; Serotonin Antagonists; Serotonin 5-HT3 Receptor Antagonists; Neurokinin-1 Receptor Antagonists; Palonosetron; Aprepitant
• Other Study ID Numbers: AS/PALO/002; 2011-003823-36 (EudraCT Number)