Clinical Trials Register

Summary
EudraCT Number:	2011-003823-36
Sponsor's Protocol Code Number:	AS/PALO/002
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2012-03-08
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2011-003823-36

A.3

Full title of the trial

Phase II randomized multicenter study of multiple doses of palonosetron plus aprepitant versus multiple doses of palonosetron alone in preventing chemotherapy-induced nausea and vomiting in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome receiving multiple days chemotherapy

Studio di fase II randomizzato di dosi multiple di palonosetron in associazione con aprepitant verso dosi multiple di palonosetron nel prevenire la nausea ed il vomito da chemioterapia in pazienti con leucemia mieloide acuta o con sindrome mielodisplasica ad alto rischio trattati con chemioterapia a giorni multipli

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A.3.2

Name or abbreviated title of the trial where available

Palonosetron + Aprepitant versus Palonosetron alone

Palonosetron + Aprepitant versus Palonosetron solo

A.4.1

Sponsor's protocol code number

AS/PALO/002

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	ASSOCIAZIONE SALENTINA ANGELA SERRA ONLUS
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Italfarmaco S.P.A
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	SC Ematologia - P.O. "Vito Fazzi" - Lecce
B.5.2	Functional name of contact point	Trial Office
B.5.3	Address:
B.5.3.1	Street Address	P.zza Filippo Muratore, 1
B.5.3.2	Town/ city	Lecce
B.5.3.3	Post code	73100
B.5.3.4	Country	Italy
B.5.4	Telephone number	+ 39 0832 661923
B.5.5	Fax number	+ 39 0832 661923
B.5.6	E-mail	quinta.ematolecce@libero.it

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	ALOXI*1FL 250MCG 5ML
D.2.1.1.2	Name of the Marketing Authorisation holder	ITALFARMACO SpA
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PALONOSETRON
D.3.9.1	CAS number	135729-56-5
D.3.9.2	Current sponsor code	Aloxi
D.3.9.4	EV Substance Code	SUB09593MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	.25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	antiemetico ed antinausea
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	EMEND*1CPS 125MG+2CPS 80MG
D.2.1.1.2	Name of the Marketing Authorisation holder	MERCK SHARP & DOHME SpA
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	APREPITANT
D.3.9.1	CAS number	NA
D.3.9.4	EV Substance Code	SUB20017
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	125
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	Antiemetico ed antinausea

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

patients with Acute Myeloid leukemia or high-risk Myelodisplastic syndrome according to IPSS score treated with AML-like multiple days chemotherapy regimen

pazienti con leucemia mieloide acuta o con sindrome mielodisplasica ad alto rischio trattati con chemioterapia AML-like a giorni multipli

E.1.1.1

Medical condition in easily understood language

Acute Myeloid leukemia or high-risk Myelodisplastic syndrome according to IPSS score

Leucemia Mieloide Acuta e Sindromi Mielodisplastiche ad alto rischio secondo l'IPSS score

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	SOC
E.1.2	Classification code	10005329
E.1.2	Term	Blood and lymphatic system disorders
E.1.2	System Organ Class	10005329 - Blood and lymphatic system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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

valutare il numero di pazienti che ottengono una risposta completa, definita come assenza di episodi di vomito o di impiego di medicazioni antiemetiche, durante il periodo dello studio (corrispondente ai giorni di somministrazione di chemioterapia e le 48 ore successive all’ultima somministrazione) nei due bracci di trattamento

E.2.2

Secondary objectives of the trial

1.Complete Response (single days only) 2.Complete Control (defined as no emetic episode, no need for rescue medication, with a maximum grade of mild nausea); 3.Percentage of patients emesis-free (no emetic episodes); 4.Presence of nausea graded according to Likert scale (none, mild, moderate and severe); 5.Time (days) to treatment failure (first emetic episode or first need of rescue medication, whichever occurs first); 6.patient global satisfaction with antiemetic therapy, as measured by a visual analogue scale (VAS); 7.Safety profile.

1.Risposta completa dei singoli giorni di terapia 2.Controllo completo (definito come risposta completa e non più di nausea lieve) 3.Percentuali di pazienti liberi da emesi (nessun episodio emetico) 4.Percentuale di nausea secondo la scala Likert (no, lieve, moderata e severa) 5.valutare il tempo al fallimento del trattamento (definito come la comparsa del primo episodio di vomito o il primo impiego di medicazioni antiemetiche); 6.valutare il livello di soddisfazione dei pazienti alla terapia antiemetica, misurata tramite una scala visiva analogica (visual analogue scale) 7.profilo di sicurezza

E.2.3

Trial contains a sub-study

E.3

Principal 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 > 18 years •ECOG 0-2 •Not pregnant or nursing •Must be able to complete the patient’s diary •Provide written informed consent

- Diagnosi di AML o HR-MDS - Età maggiore uguale a 18 anni - Pazienti candidati a trattamento chemioterapico a più giorni consecutivi (minimo 3, massimo 7) - ECOG Performance Status 0-2 - Consenso Informato Scritto - In caso di donna in età fertile uso di adeguati metodi contraccettivi - Funzionalità renale ed epatica nella norma (transaminasi ~ 2 volte il valore massimo; creatinina ~ 1,5 volte il valore massimo) - Capacità e volontà da parte del paziente di compilare il diario

E.4

Principal 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 ≥ 5 years •Unacceptable hepatic function (>2 times the upper limit of normal for liver transaminases) and renal function (creatinine >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 - treatment with experimental drug within the last month - Uncontrolled diabetes

- AML o MDS therapy-related - infezione attiva richiedente terapia antibiotica IV - precedenti neoplasie in altre sedi ad eccezione dei tumori cutanei non melanoma trattati chirurgicamente, tumore della prostata, tumore superficiale della cervice uterina, o altri tumori per i quali il paziente risulta libero da malattia da almeno 5 anni - Funzionalità epatica e/o renale alterata (> 2 volte il limite superiore di normalità) a meno che non correlato alla malattia - Malattie psichiatriche o del SNC che interferiscono con la capacità di essere aderente allo studio - Meningosi leucemica - Trattamento con farmaci sperimentali nei 30 giorni antecedenti il trattamento con palonosetron - Infarto del miocardio negli ultimi 6 mesi - Nota ipersensibilità ai 5-HT3 antagonisti - Diabete mellito non controllato - nausea e vomito pre-esistenti all'ingresso nello studio

E.5 End points

E.5.1

Primary end point(s)

the overall rate of patients achieving a complete response (defined as no emetic episode and no use of rescue medication) during the overall phase.

E.5.1.1

Timepoint(s) of evaluation of this end point

Patients will be under evaluation from Day 1 (the first day of chemotherapy) until 48 hrs after the last dose of chemotherapy. Patients will be evaluated for overall phase (from 0 hour until 48 hrs after the last dose of chemotherapy) and separately on single days.

I pazienti saranno valutati dal giorno 1 (il primo giorno di chemioterapia) fino a 48 ore dall'ultima dose di chemioterapia. I pazienti saranno valutati per l'Overall phase (dall'ora 0 fino a 48 ore dall'ultima dose di chemioterapia) eseparatamente ogni singolo giorno.

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The study will be close when the 134 patients planned will be enrolled into study

Lo studio sarà concluso quando saranno arruolati i 134 pazienti previsti

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

120

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

134

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2011-11-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-09-28

P. End of Trial
P.	End of Trial Status	Ongoing

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