Clinical Trials Register

Summary
EudraCT Number:	2012-004118-33
Sponsor's Protocol Code Number:	trapiantoover66
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:	2012-12-19
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

2012-004118-33

A.3

Full title of the trial

High-dose cyclophosphamide role in the prophylaxis of GVHD in elderly patients (66-70 years) with acute leukemia or myelodysplasia high-risk, submitted to allogenic transplant of peripheral hematopoietic progenitor cells after reduced-intensity conditioning.

Ruolo della ciclofosfamide ad alte dosi nella profilassi della GVHD in pazienti anziani (66-70 anni), affetti da leucemia acuta o mielodisplasia ad alto rischio, sottoposti a trapianto allogenico di progenitori emopoietici periferici dopo condizionamento a ridotta intensita'.

A.3.1

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

evaluation of toxicity and efficacy of a transplantation program with high dose cyclophosphamide post transplant as GVHD prophylaxis in patients who underwent to allo transplant after RIC.

valutare la tossicità e l’efficacia di una strategia trapiantologia comprendente boli di ciclofosfamide post trapianto, come profilassi per la GVHD, in pazienti affetti da LA o MDS ad alto rischio di età compresa tra 66 e 70 anni.

A.3.2

Name or abbreviated title of the trial where available

transplant over66

trapianto over66

A.4.1

Sponsor's protocol code number

trapiantoover66

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	AZIENDA OSPEDALIERA OSPEDALE NIGUARDA CA' GRANDA (A.O. DI RILIEVO NAZIONALE)
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	ematologia
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	Ematologia
B.5.2	Functional name of contact point	Dr Giovanni Grillo
B.5.3	Address:
B.5.3.1	Street Address	Piazza Ospedale Maggiore 3
B.5.3.2	Town/ city	MILANO
B.5.3.3	Post code	20162
B.5.3.4	Country	Italy
B.5.4	Telephone number	0264442668
B.5.5	Fax number	0264442033
B.5.6	E-mail	giovanni.grillo@ospedaleniguarda.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	ENDOXAN BAXTER*INIET 1FL 1G
D.2.1.1.2	Name of the Marketing Authorisation holder	BAXTER 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	Powder for solution for injection
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	CYCLOPHOSPHAMIDE MONOHYDRATE
D.3.9.1	CAS number	6055-19-2
D.3.9.4	EV Substance Code	SUB16414MIG
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	1
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	No

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

Elderly patients (66-70 years) with acute leukemia or high-risk MDS who, underwent allogenic transplant of peripheral hematopoietic progenitors after reduced-intensity conditioning.

Pazienti anziani (66-70 anni), affetti da leucemia acuta o mielodisplasia ad alto rischio, sottoposti a trapianto allogenico di progenitori emopoietici periferici dopo condizionamento a ridotta intensità.

E.1.1.1

Medical condition in easily understood language

Elderly patients (66-70 years) with acute leukemia or high-risk myelodysplasia, underwent allogenic transplant.

Pazienti anziani (66-70 anni), affetti da leucemia acuta o mielodisplasia ad alto rischio, sottoposti a trapianto allogenico.

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	15.1
E.1.2	Level	LLT
E.1.2	Classification code	10018653
E.1.2	Term	Graft-versus-host disease <GVHD>
E.1.2	System Organ Class	100000004870

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 objective is the NRM to 90 days after allogenic transplant peripheral blood stem cells after reduced-intensity conditioning in a population of elderly patients (66-70 years) with LA / high-risk MDS.

NRM a 90 giorno dal trapianto allogenico di cellule staminali periferiche dopo condizionamento a ridotta intensità in una popolazione di pazienti anziani (66-70 anni) affetti da LA/MDS ad alto rischio.

E.2.2

Secondary objectives of the trial

Secondary objectives are evaluation engraftment, chimerism, incidence of acute and chronic GVHD, DFS, OS and NRM at one year post-transplant.

Valutazione dell'attecchimento, chimerismo, incidenza della GVHD acuta e cronica, la DFS, OS e NRM ad un anno dal trapianto .

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

LAM high risk [intermediate or poor risk cytogenetics - normal karyotype with unfavorable molecular alterations - failure of the 1st cycle of induction - secondary leukemia - second complete remission] in complete remission High-risk MDS (IPSS ≥ intermediate II) ALL in complete remission Age> 66 years and <71 Availability of an HLA-matched donor hematopoietic progenitors Written informed consent

LAM ad alto rischio [citogenetica sfavorevole o intermedia – cariotipo normale con alterazioni molecolari sfavorevoli – fallimento del 1° ciclo d’induzione – leucemia secondaria – seconda remissione completa] in remissione completa MDS ad alto rischio (IPSS ≥ intermedio II) LAL in remissione completa Età > 66 anni e < 71 Disponibilità di un donatore di progenitori emopoietici HLA compatibile Consenso informato scritto.

E.4

Principal exclusion criteria

Age> 70 years Psychiatric disorders or other conditions that compromise adequate compliance to the therapeutic program Karnofsky score <60% EF <40% Renal disease (creatinine clearance <40 ml / min) Severe liver disease (ALT> 2.5 vv normal value) or acute hepatitis Deficits in lung function (FEV1, FVC, DLCO <50% of the expected after correction for hemoglobin) HIV (Human Immunodeficiency Virus) HIV Obesity morbigena, or third-degree Infections in the active phase A history of cancer of other organs and tissues not in remission or at high risk of recurrence if prolonged immunosuppressive therapy.

Età >70 anni Patologie psichiatriche o altre condizioni che compromettano un’adeguata compliance al programma terapeutico Karnofsky score < 60% FE < 40% Nefropatia (creatinina clearance <40 ml/min) Epatopatia severa (transaminasi > 2.5 vv valore normale) o epatite acuta Deficit di funzionalità respiratoria (FEV1, FVC, DLCO < 50% dell’atteso dopo correzione per emoglobina) HIV (Human Immunodeficiency Virus) sieropositività Obesità morbigena, o di terzo grado Infezioni in fase attiva Anamnesi positiva per neoplasia di altro organo o tessuto non in remissione o ad alto rischio di recidiva se prolungata terapia immunosoppressiva.

E.5 End points

E.5.1

Primary end point(s)

Mortality not related to recurrence disease in the first 90 days.

Mortalità non legata a recidiva di malattia (NRM) nei primi 90 giorni.

E.5.1.1

Timepoint(s) of evaluation of this end point

90 days

90 giorni

E.5.2

Secondary end point(s)

Secondary objectives are evaluation rate of engraftment, full chimerism, incidence of acute and chronic GVHD, DFS, OS and NRM at one year post-transplant.

Valutazione del tasso di attecchimento, chimerismo completo , incidenza della GVHD acuta e cronica, la DFS, OS e NRM ad un anno dal trapianto

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

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

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

LVLS

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)

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

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

2013-06-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-12-14

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

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