Clinical Trials Register

Summary
EudraCT Number:	2014-005697-10
Sponsor's Protocol Code Number:	FIL_GAEL
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:	2015-02-24
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

2014-005697-10

A.3

Full title of the trial

GA101-miniCHOP regimen for the treatment of elderly unfit patients with diffuse large B-cell non-Hodgkin’s lymphoma.
A phase II study of the Fondazione Italiana Linfomi (FIL).

Trattamento di prima linea per i pazienti anziani unfit con linfoma diffuso a Grandi Cellule B con la combinazione GA101-miniCHOP. Studio di fase II della Fondazione Italiana Linfomi

A.3.1

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

GA101-miniCHOP regimen for the treatment of elderly unfit patients with diffuse large B-cell non-Hodgkin’s lymphoma

Trattamento di prima linea per i pazienti anziani unfit con linfoma diffuso a Grandi Cellule B con la combinazione GA101-miniCHOP

A.3.2

Name or abbreviated title of the trial where available

FIL_GAEL

A.4.1

Sponsor's protocol code number

FIL_GAEL

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	Roche
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	Fondazione Italiana Linfomi ONLUS
B.5.2	Functional name of contact point	Segreteria FIL ONLUS
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	00390131206288
B.5.5	Fax number	00390131263455
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.2.1.1.1	Trade name	GAZYVARO
D.2.1.1.2	Name of the Marketing Authorisation holder	ROCHE REGISTRATION LIMITED
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.3.1	Product name	GAZYVARO
D.3.2	Product code	GA101
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.3.9.1	CAS number	949142-50-1
D.3.9.2	Current sponsor code	GA101
D.3.9.3	Other descriptive name	OBINUTUZUMAB
D.3.9.4	EV Substance Code	SUB32751
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
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	Yes
D.3.11.13.1	Other medicinal product type	IgG1 isotype, humanized, glycoengineered, type II anti-CD20 monoclonal antibody

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

Cd20 positive diffuse large B-cell lymphoma in unfit elderly patients

Linfoma CD20 positivo diffuso a Grandi Cellule B in pazienti anziani UNFIT

E.1.1.1

Medical condition in easily understood language

DLBCL lymphoma in elderly UNFIT patient

Linfoma DLBCL in pazienti anziani UNFIT

E.1.1.2

Therapeutic area

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

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

• To evaluate the activity of GA101-miniCHOP regimen in terms of complete response rate (CRR)

Obiettivo principale: Valutare l’attività del regime GA101-miniCHOP in termini di tasso di risposta completa (CRR)

E.2.2

Secondary objectives of the trial

• To evaluate the safety and tolerability of GA101 miniCHOP regiment in terms of adverse events
• Partial and Overall Response Rate: PR and ORR (CR+PR)
• Overall Survival (OS)
• Progression Free Survival (PFS)
• Dynamics of Comprehensive Geriatric Assessment (CGA)
• Dynamics of Quality of Life (QoL) questionnaires

Valutare la sicurezza e la tollerabilità del regime GA101-miniCHOP in termini di eventi avversi
• Tasso di risposta parziale e di risposta globale: PR e ORR (CR+PR)
• Sopravvivenza globale (OS)
• Sopravvivenza libera da progressione (PSF)
• Valutazione Geriatrica Multidimensionale (VGM)
• Questionari sulla Qualità della Vita (QoL)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Histologically proven CD20 positive Diffuse Large B-cell Lymphoma and Follicular grade IIIB lymphoma, according to WHO classification (local pathologist)
2) Age ≥ 65 years
3) No previous treatment
4) CGA assessment performed before starting treatment
5) UNFIT patients defined as follows (see Appendices A-D):
Age > 80 years with FIT profile, i.e.
ADL =6 residual functions
IADL=8 residual functions
CIRS: no comorbidity of grade 3-4 and <5 of grade 2
or Age < 80 with UNFIT profile, i.e
ADL > 5 residual functions
IADL > 6 residual functions
CIRS: no comorbidity of grade 3-4 and 5-8 co-morbidities of grade 2
6) Ann Arbor Stage I with bulky, II-IV (Appendix E)
7) At least one bi-dimensionally measurable lesion defined as > 1.5 cm in its largest dimension on CT scan
8) ECOG performance status of 0, 1, or 2 (Appendix G)
9) Adequate hematologic function (unless caused by bone marrow infiltrate), defined as follows:
Hemoglobin ≥ 10 g/dL
Absolute neutrophil count ≥ 1.5 x 109/L
Platelet count ≥ 100 x 109/L
10) LVEF >50%
11) Ability and willingness to comply with the study protocol procedure
12) Life expectancy > 6 months
13) Accessibility of patient for treatment and follow up
14) Written informed consent

1) Diagnosi di Linfoma CD20 positivo diffuso a Grandi Cellule B e linfoma e Linfoma Follicolare di grado IIIB, secondo la classificazione WHO (referti istologici locali)
2) Età ≥ 65 anni
3) Nessun trattamento precedente
4) Valutazione VGM prima di iniziare la terapia
5) Pazienti UNFIT definiti come segue:
Età > 80 anni con profilo FIT, i.e.
ADL =6 funzioni residue
IADL=8 funzioni residue
CIRS: nessuna comorbidità di grado 3-4 e <5 di grado 2
O età < 80 anni con profilo UNFIT, i.e.
ADL > 5 funzioni residue
IADL > 6 funzioni residue
CIRS: nessuna comorbidità di grado 3-4 e 5-8 comorbidità di
grado 2
6) Stadio Ann Arbor con bulky, II-IV
7) Almeno una lesione misurabile bi-dimensionalmente, definita come > 1.5 cm nella sua massima dimensione alla TC
8) ECOG performance status pari a 0, 1, o 2
9) Adeguata funzione ematologica (a meno che non sia dovuta a infiltrazione del midollo osseo), definita come segue:
Emoglobina ≥ 10 g/dL
Conta assoluta di neutrofili ≥ 1.5 x 109/L
Conta delle piastrine ≥ 100 x 109/L
10) LVEF >50%
11) Capacità e volontà di rispettare le procedure previste dal Protocollo
12) Aspettativa di vita > 6 mesi
13) Disponibilità del paziente a sottoporsi al trattamento e al follow-up
14) Consenso Informato scritto.

E.4

Principal exclusion criteria

1) History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
2) Contraindication to any of the individual components of CHOP, including prior receipt of anthracyclines
3) History of other malignancies within 5 years prior to study entry except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer
4) Stage I without bulky
5) Patients with transformed lymphoma
6) Prior therapy for DLBCL, with the exception of nodal biopsy or local irradiation
7) Previous exposure to cytotoxic agents
8) Suspect or clinical evidence of CNS involvement by lymphoma
9) HBsAg, HCV or HIV positivity; isolated HBcAb positivity is accepted only with concomitant treatment with Lamivudine
10) AST /ALT > twice upper the normal range; bilirubin > twice upper the normal range; serum creatinine > 2.5 mg /dl (unless these abnormalities were related to the lymphoma)
11) Evidence of any severe active acute or chronic infection
12) Concurrent co-morbid medical condition which might exclude administration of full dose chemotherapy

1) Anamnesi di gravi reazioni allergiche o anafilattiche agli anticorpi monoclonali umanizzati o murini o nota sensibilità o allergia ai prodotti murini
2) Controindicazione a uno qualsiasi dei singoli componenti del CHOP, inclusa una precedente somministrazione di antracicline
3) Storia clinica di altre neoplasie nei 5 anni precedenti all’ingresso in studio, ad eccezione di carcinoma della cervice in situ o carcinoma a cellule basali o squamose della pelle, adeguatamente trattati
4) Stadio I senza bulky
5) Pazienti con linfoma trasformato
6) Precedente terapia per DLBCL, ad eccezione della biopsia linfonodale o dell’irradiazione locale
7) Precedente esposizione ad agenti citotossici
8) Sospetto o evidenza clinica di coinvolgimento del SNC da parte del linfoma
9) Positività a HBsAg, HCV o HIV; un’isolata positività ad HBcAB è accettata solo in presenza di trattamento concomitante con Lamivudina
10) AST/ALT > 2 volte dei valori normali; bilirubina > 2 volte dei valori normali; creatinina sierica > 2,5 mg/dl (a meno che queste anomalie siano correlate al linfoma)
11) Evidenza di qualsiasi grave infezione attiva, acuta o cronica
12) Condizione medica caratterizzata da concomitante comorbidità che potrebbe impedire la somministrazione di chemioterapia a pieno dosaggio

E.5 End points

E.5.1

Primary end point(s)

• Complete Response Rate after 10 infusions of GA101 and 6 cycles of miniCHOP. The response rate to therapy will be based a central Independent Review Committee of response that will not consider the results of FDG-PET but will only use the conventional CT scan images (International Criteria, B. Cheson, JCO 1999)

Tasso di Risposta Completa dopo 10 infusioni di GA101 e 6 cicli di miniCHOP. Il tasso di risposta alla terapia sarà basato sui risultati formulati da un Comitato di Revisione Indipendente che non considererà i risultati delle FDG-PET, ma utilizzerà solo le immagini TAC convenzionali (Criteri Internazionali di B. Cheson, JCO 1999).

E.5.1.1

Timepoint(s) of evaluation of this end point

36 months from first patient in

a 36 mesi (3 anni) dal primo arruolamento

E.5.2

Secondary end point(s)

• Rate of Adverse Events
• Partial and Overall Response Rate (PRR, ORR)
• Overall Survival (OS)
• Progression Free Survival (PFS)
• Change in ADL, IADL and CIRS
• Change in QoL (EORTC QLQ C30)

Tasso di Eventi Avversi
• Tasso di risposta parziale e globale (PRR, ORR)
• Sopravvivenza globale (OS)
• Sopravvivenza libera da progressione (PFS)
• Variazione dei risultati nelle schede ADL, IADL e CIRS
• Variazione delle risposte ai questionari QoL (EORTC QLQ C30)

E.5.2.1

Timepoint(s) of evaluation of this end point

Rate of Adverse Events, Partial and Overall Response Rate (PRR, ORR), Change in ADL, IADL and CIRS, Change in QoL (EORTC QLQ C30): 36 months from first patient in;
Overall Survival (OS)
Progression Free Survival (PFS): from 60 months from first patient in

• Tasso eventi avversi, tasso di risposta parziale e globale, valutazione schede ADL, IADL, CIRS e questionari QoL: a 36 mesi (3 anni) dal primo arruolamento.
• Sopravvivenza globale (OS), sopravvivenza libera da progressione (PFS): a 60 mesi (5 anni) dal primo arruolamento

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

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

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.1.1.1

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)

none

nessuno

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

2015-04-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-03-25

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

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