Clinical Trials Register

Summary
EudraCT Number:	2013-001639-38
Sponsor's Protocol Code Number:	MDS/2013
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2016-07-26
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

Czechia - SUKL

A.2

EudraCT number

2013-001639-38

A.3

Full title of the trial

Contribution to verify the effectiveness of adding granulocyte stimulating factor (G-CSF) to therapy 5 - Azacitidine patients with the high risk Myelodysplastic syndrome.

Příspěvek k ověření účinnosti přidání granulocyty stimulujícího faktoru (G-CSF) k dosavadní terapii (5 – AZACITIDINEM) nemocných s myelodyspalstickým syndromem.

A.3.1

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

Verification of the effectiveness of adding granulocyte stimulating factor (G-CSF) to therapy patients with myelodysplastic syndrome (MDS) in high-risk disease.

Ověření účinností přidání granulocyty stimulujícího faktoru (G-CSF) k dosavadní terapii nemocných s Myelodysplastickým syndromem (MDS) ve vysokém riziku onemocnění.

A.3.2

Name or abbreviated title of the trial where available

GA-MDS/ 2013

A.4.1

Sponsor's protocol code number

MDS/2013

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	1st Dep. of Medicine, General University Hospital (VFN) in Prague
B.1.3.4	Country	Czech Republic
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	1st Dep. of Medicine, General University Hospital in Prague (VFN)
B.4.2	Country	Czech Republic
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	1st Dep. of Medicine, General University Hospital in Prague (VFN
B.5.2	Functional name of contact point	prof. Tomas Stopka, MD
B.5.3	Address:
B.5.3.1	Street Address	U Nemocnice 5
B.5.3.2	Town/ city	Prague
B.5.3.3	Post code	12800
B.5.3.4	Country	Czech Republic
B.5.4	Telephone number	420732561944
B.5.5	Fax number	420224963556
B.5.6	E-mail	Tomas.Stopka@lf1.cuni.cz

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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	AZACITIDINE 25 mg/ml (Vidaza)
D.2.1.1.2	Name of the Marketing Authorisation holder	CELGENE EUROPE LIMITED
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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.3.1	Product name	AZACITIDINE 25 mg/ml
D.3.4	Pharmaceutical form	Powder for suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
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.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	FILGRASTIM 30 MU (60 MU/ml) FILGRASTIM 48 MU (96 MU/ml)
D.2.1.1.2	Name of the Marketing Authorisation holder	Hexal AG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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.3.1	Product name	FILGRASTIM
D.3.4	Pharmaceutical form	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
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)	Yes
	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	Yes
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

Patients with the diagnosis:HR-MDS, AML less than 30% myeloblasts and CMML II, who will be treated with AZA or AZA + G-CSF.

Pacienti s diagnózou: HR-MDS, AML do 30% myeloblastů a CMML II, které budou lečeny terapii AZA nebo AZA + G-CSF.

E.1.1.1

Medical condition in easily understood language

High risk Myelodysplastic sy., Acute myeloid leukemia less than 30% myeloblasts and chronic myelomonocytic leukemia II, who will be treated with therapy Azacitidine or Azacitidine + G-CSF.

Myelodysplastický syndrom s vysokým riskem, Akutní myeloidní leukemie do 30 % myeloblastů a Chronická myelomonocytární leukemie II, budou léčeny terapii Azacitidinem nebo Azacitidinem + G-CSF.

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Prolongation of survival, prolong transformation to acute leukemia, reduce the incidence of infection and hospitalization, achieving transfusion independence and improving the quality of of life of patients with HR-MDS, AML and 30% myeloblasts and CMML II.

Prodloužení přežívání, prodloužení doby transformace do akutní leukemie, snížení výskytu infektů a počtu hospitalizaci, dosažení transfuzní nezávislostí a zvýšení kvality života pacientů s HR-MDS, AML do 30 % myeloblastů a CMML II.

E.2.2

Secondary objectives of the trial

Determine the correlation of genetic changes and clinical response to a given therapy.
To study the effectiveness of the selected treatment at the molecular level at the epigenetic parameters

Zjistit vztah genetických změn a klinické odpovědí na podávanou terapii.
Studovat efektivitu zvolené léčby na molekulární úrovni na úrovni epigenetických parametrů

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients indicated for the treatment with Vidaza who are not eligible for haematopoietic stem cell transplantation with:

- Myelodysplastic syndrome (MDS) second intermediate risk and high-risk (International Prognostic Scoring System, IPSS)

- Chronic myelomonocytic leukemia without myeloproliferative features (CMML II according to WHO)

- Acute myeloid leukemia (AML) with 20-30% blasts and dysplasia in several cell lines, according to the classification of WHO,

2. Patients who signed informed consent;
3. Patients ≥ 18 years;
4. Patients without significant comorbidities (eg, comorbidities heart, liver, blood vessels, brain), reducing the chance of survival of less than six months;
Patients unable to undergo therapy and plan visits, including necessary tests.

1. Pacienty, indikované k léčbě s Vidaza, kteří nejsou způsobilí pro transplantaci hematopoetických kmenových buněk s:

- myelodysplastickým syndromem (MDS) intermediárního rizika 2. stupně a vysokého rizika (International Prognostic Scoring System, IPSS),

- chronickou myelomonocytární leukemií bez myeloproliferativních rysů (CMML II dle WHO),

- akutní myeloidní leukemií (AML) s 20-30 % blastů a dysplazií ve více buněčných liniích, podle klasifikace WHO,

2. Pacienty, kteří podepsali informovaný souhlas;
3. Pacienty ≥18 let;
4. Pacienty bez závažných komorbidit (například doprovodných onemocnění srdce, jater, cév, mozku), snižujících možnost přežití na méně než 6 měsíců;
Pacienty schopni absolvovat terapii a plán návštěv, včetně nutných vyšetření.

E.4

Principal exclusion criteria

1. The presence of other hematological, internal disease that limits survival for less than six months.
2. Pregnant women or women in lactation period
3. Man or woman of childbearing age without the willingness to use safe contraception. Details of the method of contraception, see the document "Information for the Patient / Informed Consent Form".

1. Přítomnost jiného hematologického, interního onemocnění, které limituje přežívání na kratší dobu než 6 měsíců.
2. Těhotná žena nebo žena v období laktace
3. Žena či muž ve fertilním veku bez ochoty užívat bezpečnou antikoncepci. Podrobnosti o způsobu antikoncepce viz dokument „Informace pro pacienta/Formulář informovaného souhlasu“.

E.5 End points

E.5.1

Primary end point(s)

E.5.1.1

Timepoint(s) of evaluation of this end point

Extension of survival and time transform by 50%

prodložení přeživaní a doby tranformace o 50%

E.5.2

Secondary end point(s)

Determine the correlation of genetic changes and clinical response to a given therapy.
To study the effectiveness of the selected treatment at the molecular level at the epigenetic parameters

Zjistit vztah genetických změn a klinické odpovědí na podávanou terapii.
Studovat efektivitu zvolené léčby na molekulární úrovni na úrovni epigenetických parametrů

E.5.2.1

Timepoint(s) of evaluation of this end point

Achieving the anticipated goals for the duration of the study

Dosažení přepokladaných cílů po dobu trvaní studie

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

E.6.5

Efficacy

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

Yes

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Research on molecular characteristics of malignant disease during the proposed treatment.

Výzkum molekularních charakteristik maligních onemocnění v průběhu navrhované léčby.

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)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

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

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

Ayacitidin bez G-CSF

Azacitidin without G-CSF

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the 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

Yes

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

Reasons for termination-at his own request of the patient, the disease progression (increase to AML stage) after 8 cycle without any response (IWG 2006), to disease progression (or relapse after reaching CR). The need other therapy and the occurrence of adverse events that affect the health of the patient and his cooperation (compliance) so that the doctor will decide on his break.

Důvody ukončení –na vlastní žádost pacienta, progrese základního onemocnění (nárůst nádorových blastů do stadia AML), po 8. cyklu bez jakékoli odpovědi (IWG 2006), dojde-li kdykoli v průběhu terapie k progresi (či relapsu při dosažení CR) onemocnění. Nutnost jiné terapie a při výskytu nežádoucích účinků, které ovlivní zdravotní stav pacienta a jeho spolupráce (compliance) natolik, že lékař rozhodne o jeho přerušení

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

E.8.9.2

In all countries concerned by the trial years

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

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.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

135

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)

None

Neni

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

2016-12-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-05-19

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

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