Clinical Trials Register

Summary
EudraCT Number:	2012-001404-38
Sponsor's Protocol Code Number:	FIL_GEMRO
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-07-23
Trial results	View 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

2012-001404-38

A.3

Full title of the trial

Phase IIa study on the role of Gemcitabine plus Romidepsin (GEMRO regimen) in the treatment of relapsed/refractory peripheral T-cell lymphoma patients.

Studio di fase IIa sul ruolo di gemcitabina e romidepsina (regime GEMRO) nel trattamento di pazienti ricaduti/refrattari con linfoma T periferico. (FIL_GEMRO)

A.3.1

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

Phase IIa study on the role of Gemcitabine plus Romidepsin (GEMRO regimen) in the treatment of relapsed/refractory peripheral T-cell lymphoma patients.

Studio di fase IIa sul ruolo di gemcitabina e romidepsina (regime GEMRO) nel trattamento di pazienti ricaduti/refrattari con linfoma T periferico.

A.3.2

Name or abbreviated title of the trial where available

FIL_GEMRO

A.4.1

Sponsor's protocol code number

FIL_GEMRO

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	FONDAZIONE ITALIANA LINFOMI 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	Celgene
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Fondazione Italiana Linfomi ONLUS
B.5.2	Functional name of contact point	Segreteria
B.5.3	Address:
B.5.3.1	Street Address	Via Venezia 16
B.5.3.2	Town/ city	Alessandria
B.5.3.3	Post code	15121
B.5.3.4	Country	Italy
B.5.4	Telephone number	0131/206071
B.5.5	Fax number	0131/263455
B.5.6	E-mail	segreteria@filinf.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.2.1.2	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	Concentrate for 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	GEMCITABINE HYDROCHLORIDE
D.3.9.1	CAS number	122111-03-9
D.3.9.4	EV Substance Code	SUB02324MIG
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	ISTODAX
D.2.1.1.2	Name of the Marketing Authorisation holder	CELGENE CORPORATION
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/05/328 PTCL EU/3/05/279 CTCL
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Powder and solvent for 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	ROMIDEPSIN
D.3.9.4	EV Substance Code	SUB26362
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	10
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	Medicinale di sintesi

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

Relapsed/refractory peripheral T-cell lymphoma patients.

Pazienti ricaduti/refrattari con linfoma T periferico.

E.1.1.1

Medical condition in easily understood language

Relapsed/refractory peripheral T-cell lymphoma patients.

Pazienti ricaduti/refrattari con linfoma T periferico.

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	14.1
E.1.2	Level	HLGT
E.1.2	Classification code	10025321
E.1.2	Term	Lymphomas non-Hodgkin's T-cell
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

To evaluate the efficacy, as assessed by the CR rate, of GEMRO salvage treatment in PTCL.

Valutare l’efficacia del regime di chemioterapia GEMRO (gemcitabina e romidepsina), in termini di RC, come trattamento di salvataggio nei linfomi T periferici.

E.2.2

Secondary objectives of the trial

To assess the safety and feasibility of concomitant GEMRO therapy in this setting.

Valutare la sicurezza e la fattibilita' di una terapia concomitante GEMRO in questa tipologia di pazienti.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients with histological diagnosis of PTCL according to the WHO classification. 2. Age ≥ 18 years. 3. Relapsed (³1) or refractory to conventional chemotherapy/radiotherapy. 4. Stage I–IV according to the Ann Arbor staging System. 5. ECOG Performance status £2. 6. Normal renal and hepatic functions. 7. Laboratory test results as follows: • Serum creatinine ≥2.0 mg/dL • Total bilirubin ≥1.5 mg/dL • AST (SGOT) and ALT (SGPT) £2 x ULN or £5 x ULN if hepatic metastases are present • Negative HIV HCV and HBV status. 8. Adequate bone marrow reserve: Platelet count>100X109 cells/L or platelet count >75X109 cells/L if bone marrow disease involvement, absolute neutrophile count (ANC)> 1,5 X109, hemoglobin>8 g/dl. 9. Able to adhere to the study visit schedule and other protocol requirements. 10. Cardiac ejection fraction (MUGA scan or echocardiography) > 45%. 11. Life expectancy > 6 months. 12. Females of childbearing potential (FCBP) must have a negative serum or urine β-hCG pregnancy test result within 7 days prior to the first dose of study drug. Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy. 13. Both females of childbearing potential and males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days after the last dose of study drug. 14. Measurable disease of at least 2 cm as detected by CT scan, assessed by site radiologist. 15. Patients or they legally authorized representative must provide written informed consent.

1)Diagnosi istologica di linfoma T periferico in accordo con la classificazione WHO 2) Eta' ≥ 18 anni 3) Pazienti ricaduti o refrattari alla terapia convenzionale (chemioterapia/radioterapia) 4) Stadio I-IV in accordo con la classificazione di Ann Arbor 5) ECOG performance status ≤2 6) Funzioni renali ed epatiche nella norma 7) I seguenti risultati dei test di laboratorio: - La creatinina sierica ≥  2,0 mg / dL - Bilirubina totale ≥ 1,5 mg / dL - AST (SGOT) e ALT (SGPT) ≤2 x ULN o ≤5 x ULN, se sono presenti metastasi epatiche - Negativita' per HIV, HCV e HBV 8) Adeguata riserva di midollo osseo: piastrine >100x109 cell/L oppure>75x109 cell/L se e' presente un coinvolgimento midollare della malattia; conta assoluta dei neutrofili ≥1.5 x109/L, emoglobina ≥ 8g/dl 9) In grado di aderire al programma di visite dello studio e a quanto richiesto dal protocollo 10) Frazione di eiezione cardiaca (MUGA scan o ecocardiografia)> 45% 11) Aspettativa di vita > di 6 mesi 12) Le donne in eta' fertile (FCBP) deve avere test di gravidanza negativo entro i 7 giorni precedenti la prima dose del farmaco in studio. Le donne non fertili sono quelle che sono in post-menopausa da almeno un 1 anno o che hanno subito la legatura bilaterale delle tube o l’isterectomia. 13) Sia le donne in eta' fertile che gli uomini che hanno partner in eta' fertile devono accettare di utilizzare un metodo contraccettivo efficace durante lo studio e per 30 giorni dopo l'ultima dose del farmaco in studio. 14) Malattia misurabile di almeno 2 cm, come rilevato dal CT scan, valutato dal sito radiologo. 15) Firma del consenso informato allo studio

E.4

Principal exclusion criteria

1. Any serious active disease or co-morbid medical condition (according to investigator's decision) 2. Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the subject has been free of the disease for ≥ 3 years, 3. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form, 4. Patients with congenital long QT syndrome, history of significant cardiovascular disease and/or taking drugs leading to significant QT prolongation, 5. Corrected QT interval > 480 msec (using the Fredericia formula) 6. Low K+ (<3.8 mmol/L) and low Mg+ (<0.85 mmol/L) levels, except if corrected before beginning the chemotherapy 7. Pregnant or lactating females or men or women of childbearing potential not willing to use an adequate method of birth control for the duration of the study. 8. Previous exposure to romidepsine or gemcitabine; 9. CNS disease (meningeal and/or brain involvement by lymphoma) or testicular involvement; 10. History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances; 11. Active opportunistic infection;

1) Qualsiasi malattia grave in atto o condizione medica co-morbosa (in base alla decisione del ricercatore). 2) Precedente storia di neoplasie diverse dal linfoma (ad eccezione di carcinoma basocellulare o squamoso della cute o carcinoma in situ della cervice o della mammella) a meno che il soggetto non sia indenne da questa malattia da almeno 3 anni. 3) Qualsiasi grave condizione medica, alterazione di laboratorio, o una malattia psichiatrica che possa impedire al soggetto di firmare il modulo di consenso informato. 4) I pazienti con sindrome congenita del QT lungo, storie significative di malattie cardiovascolari e / o assunzioni di farmaci che portano ad un significativo prolungamento del QT . 5) Intervallo QT corretto> 480 msec (con la formula Fredericia). 6) Bassi livelli di K+ (<3,8 mmol / L) e Mg + (<0,85 mmol / L), se non corretti prima di iniziare la chemioterapia. 7) Donne gravide o in allattamento o uomini e donne in eta' fertile che non sono disposte a utilizzare un metodo adeguato di controllo delle nascite per tutta la durata dello studio. 8) Precedente esposizione a romidepsina o gemcitabina. 9) Malattie del SNC (meningea e / o coinvolgimento del cervello da linfoma) o coinvolgimento testicolare. 10) Storia clinica rilevante legata a fenomeni di insufficienza epatica o renale; significativi disturbi cardiaci, vascolari, polmonari, gastrointestinali, endocrinologici, neurologici, reumatologici, disturbi ematologici, psichiatrici, o metabolica. 11) Infezioni opportunistiche attive.

E.5 End points

E.5.1

Primary end point(s)

The proportion of patients with complete remission (CR) according to the Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007).

La proporzione di pazienti in RC in accordo con i Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007).

E.5.1.1

Timepoint(s) of evaluation of this end point

6 mounths

6 mesi

E.5.2

Secondary end point(s)

The Overall Response Rate (ORR=CR+CRu+PR) is defined as the proportion of patients who achieve CR, CRu or PR relative to the per-protocol population. Disease response and progression will be evaluated according to the “Revised Response Criteria” for malignant lymphoma (Cheson et al. 2007). Duration of response (CR, Cru or PR) will be calculated from the date of initial documentation of response, to the date of the first documented evidence of PD (or relapse).

ORR, definito come la proporzione di pazienti che raggiungono RC, RCu o RP.

E.5.2.1

Timepoint(s) of evaluation of this end point

18 mounths

18 mesi

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

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

E.8.1.1

Randomised

E.8.1.2

Open

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)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

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)

Yes

F.1.2.1

Number of subjects for this age range:

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

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)

Patients will be followed as per normal clinical practice.

I pazienti saranno seguiti come da normale pratica clinica.

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

2012-07-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-06-12

P. End of Trial
P.	End of Trial Status	Completed

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