Clinical Trials Register

Summary
EudraCT Number:	2015-001998-40
Sponsor's Protocol Code Number:	GO29833
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:	2021-01-22
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2015-001998-40

A.3

Full title of the trial

A PHASE Ib/II STUDY EVALUATING THE SAFETY AND EFFICACY OF OBINUTUZUMAB IN COMBINATION WITH POLATUZUMAB VEDOTIN AND VENETOCLAX IN PATIENTS WITH RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA AND RITUXIMAB IN COMBINATION WITH POLATUZUMAB VEDOTIN AND VENETOCLAX IN PATIENTS WITH RELAPSED OR REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA

STUDIO DI FASE IB/II TESO A VALUTARE LA SICUREZZA E L’EFFICACIA DI OBINUTUZUMAB IN COMBINAZIONE CON POLATUZUMAB VEDOTIN E VENETOCLAX IN PAZIENTI AFFETTI DA LINFOMA FOLLICOLARE REFRATTARIO O RECIDIVANTE E RITUXIMAB IN COMBINAZIONE CON POLATUZUMAB VEDOTIN E VENETOCLAX IN PAZIENTI CON O LINFOMA DIFFUSO A GRANDI CELLULE B REFRATTARIO O RECIDIVANTE

A.3.1

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

A Study to evaluate the safety and efficacy of Obinutuzumab in combination with Polatuzumab Vedotin and Venetoclax in patients with relapsed or refractory follicular Lymphoma and Rituximab in combination with Polatuzumab Vedotin and Venetoclax in patients with relapsed or refractory diffuse large B-cell Lymphoma

Safety and Efficacy of Obinutuzumab, in Combination with Polatuzumab Vedotin and Venetoclax in Patients with Relapsed or Refractory, Follicular or Diffuse Large B Cell Lymphoma

Uno studio per valutare sicurezza e l'efficacia di Obinutuzumab, in combinazione con Polatuzumab Vedotin e Venetoclax in pazienti affetti da Linfoma Follicolare e Rituximab in combinazione con Polatuzumab Vedotin e Venetoclax in pazienti affetti da Linfoma diffuso a grandi cellule B refrattario o recidivante

A.3.2

Name or abbreviated title of the trial where available

A Study to Evaluate Safety and Efficacy of Obinutuzumab, in Combination with Polatuzumab Vedotin and

Uno studio per valutare sicurezza e l'efficacia di Obinutuzumab, in combinazione con Polatuzumab Ved

A.4.1

Sponsor's protocol code number

GO29833

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	F. HOFFMANN - LA ROCHE LTD.
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Genentech Inc. c/o F. Hoffmann La Roche Ltd.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Genentech Inc. c/o F. Hoffmann La Roche Ltd.
B.5.2	Functional name of contact point	Trial Information Support Line-TISL
B.5.3	Address:
B.5.3.1	Street Address	Grenzacherstrasse 124
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4070
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	0000041
B.5.5	Fax number	00000041
B.5.6	E-mail	global.rochegenentechtrials@roche.com

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	No
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	polatuzumab vedotin
D.3.2	Product code	[DCDS4501A]
D.3.4	Pharmaceutical form	Powder 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	POLATUZUMAB VEDOTIN
D.3.9.2	Current sponsor code	NA
D.3.9.4	EV Substance Code	SUB177827
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	170
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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.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	Gazyvaro
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration GmbH
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	na
D.3.2	Product code	[na]
D.3.4	Pharmaceutical form	Concentrate 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	Obinutuzumab
D.3.9.1	CAS number	949142-50-1
D.3.9.2	Current sponsor code	na
D.3.9.4	EV Substance Code	SUB32751
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	1000
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Gazyvaro is a humanized and glycoengineered mAB
D.IMP: 3
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	No
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	Venetoclax
D.3.2	Product code	[GDC-0199]
D.3.4	Pharmaceutical form	Film-coated tablet
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	VENETOCLAX
D.3.9.2	Current sponsor code	GDC-0199
D.3.9.4	EV Substance Code	SUB176260
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	100
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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: 4
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	MabThera
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration GmbH
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	NA
D.3.2	Product code	[NA]
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	RITUXIMAB
D.3.9.1	CAS number	174722-31-7
D.3.9.2	Current sponsor code	NA
D.3.9.4	EV Substance Code	SUB12570MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
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	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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

Relapsed or refractory, follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL)

PAZIENTI CON LINFOMA FOLLICOLARE (FL) O LINFOMA DIFFUSO A GRANDI CELLULE B (DLBCL) RECIDIVANTE O REFRATTARIO (R/R)

E.1.1.1

Medical condition in easily understood language

FL is a low grade tumor that develops slowly and DLBCL is an aggressive tumor that develops rapidly

FL è un tumore di basso grado che si sviluppa lentamente e DLBCL è un tumore aggressivo che si sviluppa rapidamente

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	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10012857
E.1.2	Term	Diffuse large cell lymphoma (Diffuse large B-cell lymphoma) (Working Formulation) refractory
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10012855
E.1.2	Term	Diffuse large cell lymphoma (Diffuse large B-cell lymphoma) (Working Formulation)
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10012856
E.1.2	Term	Diffuse large cell lymphoma (Diffuse large B-cell lymphoma) (Working Formulation) recurrent
E.1.2	System Organ Class	100000004864

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 determine the recommended Phase II dose (RP2D) for polatuzumab vedotin (Pola) and Venetoclax (Ven) when given in combination with a fixed dose of Obinutuzumab (Obi) in R/R FL and the RP2D of V when given in combination with a fixed dose of Pola and rituximab (R) in R/R DLBCL on the basis of incidence of dose limiting toxicities (DLTs) during the first cycle of study treatment
• To evaluate the safety and tolerability of G+Pola+V and R+Pola+V based on nature, frequency, severity, timing of adverse events and DLTs, changes in vital signs, electrocardiogram (ECGs), and clinical laboratory results during and following study treatment administration
• To evaluate the efficacy of G+Pola+V in patients with R/R FL and R+Pola+V in patients with R/R DLBCL as determined by the Independent Review Committee (IRC) based on complete response (CR) at end of induction (EOI), on the basis of positron emission tomography computerized tomography (PET CT) scans

• Determinare la dose raccomandata per la fase II(RP2D) di polatuzumab vedotin(Pola) e venetoclax (V) somministrati in combinazione con una dose fissa di obinutuzumab (G) in FL R/R e la RP2D di V somministrato con una dose fissa di Pola e rituximab (R) in DLBCL R/R in base all'incidenza delle tossicità dose limitanti (DLT) durante il primo ciclo del trattamento dello studio
• Valutare la sicurezza e la tollerabilità di G +Pola+V R+Pola+V sulla base della natura, frequenza, gravità e momento di comparsa degli eventi indesiderati, incluse le DLT; cambiamenti nei parametri vitali, nell'ECG e nei risultati degli esami clinici di laboratorio durante e dopo la somministrazione del trattamento dello studio
• Valutare l'efficacia del trattamento G + Pola + V in pazienti con FL R/R e R+Pola+V in pazienti con DLBCL R/R secondo quando determinato dal comitato di revisione indipendete (IRC) base sulla della Risposta completa (CR) al termine dell'induzione (EOI), utilizzando le scansioni PET-TAC

E.2.2

Secondary objectives of the trial

• To evaluate the efficacy of G+Pola+V and maintenance treatment with G+V in patients with R/R FL and R+Pola+V and consolidation treatment with R+V in patients with R/R DLBCL based on CR at EOI as determined by the IRC and by the investigator on the basis of PET-CT scans or CT scans alone, objective response determined by the IRC and the Investigator on the basis of PET CT scans or CT scans alone, best response of CR or PR during the study determined by the Investigator on the basis of CT scans alone
• To characterize the pharmacokinetic profiles of G, R, Pola, and V when given in combination based on the observed serum concentration of G, R, serum and plasma concentrations of Pola and relevant analytes and plasma concentration of V at specified timepoints
• To evaluate the immune response to G and Pola based on incidence of human anti-human antibodies (HAHA) to G and anti-therapeutic antibody (ATA) to Pola during the study relative to the prevalence of HAHAs and ATAs at baseline

-valutare l'efficacia del trattamentoG+Pola+V e del trattamento di mantenimento con G+V in pazienti con FL R/R e R+Pola+V e trattamento di consolidamento con R+V in pazienti con DLBCL sulla base del CR all'EOI secondo quanto determinato dall'IRC e dallo sperimentatore sulla base delle scansioniPET-TAC o scansioniTAC da sole;Migliore risposta di CR o PR durante lo studio,come determinato dallo sperimentatore sulla base delle scansioniTAC da sole
-caratterizzare i profili PK diG,R,Pola eV,quando somministrati in combinazione,sulla base della concentrazione sierica di G e R e su concentrazioni sieriche e plasmatiche di polavedotin Pola e analiti rilevanti e concentrazione plasmatica di V osservata in determinati momenti di valutazione
-Valutare la risposta immunitaria a G e ola sulla base di incidenza di anti-anticorpi umani (HAHA) diretti contro G ed anticorpi anti-terapeutici(ATA)diretti contro Pola, rispetto alla prevalenza di HAHA e ATA al baseline

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Age >=18 years
- Eastern cooperative oncology group (ECOG) performance status of 0, 1, or 2
- For G + Pola + V treatment group: R/R FL after treatment with at least 1 prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal
antibody and for which no other more appropriate treatment option exists, as determined by the investigator
- For R + Pola + V treatment group: R/R DLBCL after treatment with at least 1 prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody, with no
curative option as determined by the investigator
- Histologically documented CD20-positive non Hodgkin's lymphoma
- Fluorodeoxyglucose (FDG)-avid lymphoma (PET-positive lymphoma)
- At least one bi-dimensionally measurable lesion (>1.5 cm in its largest dimension by CT scan or magnetic resonance imaging [MRI])
- Patients enrolled in the dose escalation phase with relapsed or refractory follicular lymphoma after treatment with at least 1 prior chemoimmunotherapy regimen that included an anti CD20 monoclonal antibody and for which no other more appropriate treatment option exists, as determined by the investigator
- Patients enrolled in the expansion phase with relapsed or refractory diffuse large B-cell lymphoma after treatment with at least 1 prior chemoimmunotherapy regimen that included an anti CD20 monoclonal antibody with no curative option as determined by the investigator
- For women of childbearing potential: Agreement to remain abstinent or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 12 months after the last dose of polatuzumab vedotin, 30 days after the last dose of venetoclax, 12 months after the last dose of rituximab or at least 18 months after the last dose of obinutuzumab
- For men: Agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm

• Età pari o superiore a 18 anni
• Stato di validità (ECOG) di 0, 1 o 2.
• Per il gruppo di trattamento G+Pola+V: FL R/R dopo trattamento con almeno 1 regime chemioimmunoterapico precedente che includeva un anticorpo monoclonale anti CD-20 e
per i quali non esistano altre opzioni terapeutiche più appropriate, secondo quanto determinato dallo Sperimentatore
• Per il gruppo di trattamento R+Pola+V: DLBCL R/R dopo trattamento con almeno 1 regime chemioimmunoterapico precedente che includeva un anticorpo monoclonale anti CD-
20 e per i quali non esistano opzioni curative, secondo quanto determinato dallo Sperimentatore

• Linfoma non-Hodgkin CD20-positivo, documentato istologicamente,
• Linfoma fluorodeossiglucosio avido (cioè, linfoma positivo alla PET)
• Almeno una lesione misurabile a livello bidimensionale (>1,5 cm nella dimensione maggiore mediante TAC o RM)
• Per i pazienti arruolati nella fase di incremento della dose: FL R/R dopo il trattamento con almeno 1 regime di chemioimmunoterapia pregresso che includeva un anticorpo monoclonale anti-CD20 e per il quale non esiste altra opzione di trattamento più appropriata, secondo il giudizio dello sperimentatore
• Per i pazienti arruolati nella fase di espansione con linfoma a cellule B classificato dopo il trattamento con almeno 1 precedente regime di chemioimmunoterapia che includeva un anticorpo monoclonale anti-CD20 e per il quale non esiste alcuna opzione di trattamento più appropriata, secondo il giudizio dello sperimentatore.
- Per le donne in età fertile: consenso a praticare l'astinenza o ad utilizzare metodi contraccettivi che abbiamo un tasso di fallimento < 1% l'anno, durante il periodo di trattamento, e per almeno 12 mesi dopo l'ultimal'ultima dose di venetoclax, 12 mesi dopo l'ultima dose di polatuzumab vedotin, 30 giorni dopo l'ultima dose di venetoclax, 12 mesi dopo l’ultima dose di rituximab o almeno 18 mesi dopo l'ultima dose di obinutuzumab.
- Per gli uomini: consenso a praticare l'astinenza o ad utilizzare misure contraccettive e consenso all'astenersi dal donare sperma.

E.4

Principal exclusion criteria

- Known CD20 negative status at relapse or progression
- Prior allogeneic stem-cell transplantation (SCT)
- Completion of autologous SCT within 100 days prior to Day 1 of Cycle 1
- Prior standard or investigational anti cancer therapy
- Clinically significant toxicity from prior therapy that has not resolved to Grade <=2 (per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0) prior to Day 1 of Cycle 1
- Grade 3b follicular lymphoma
- History of transformation of indolent disease to DLBCL
- Current Grade >1 peripheral neuropathy
- Central nervous system (CNS) lymphoma or leptomeningeal infiltration
- Treatment with systemic corticosteroids >20 mg/day prednisone or equivalent
- Allergy to murine products or any of the components of the Obi, Pola, or Ven
- History of progressive multifocal leukoencephalopathy, any significant and uncontrolled concomitant disease, or any other malignancy that could affect compliance with the protocol or interpretation of results
- Inadequate hematologic function

• Stato CD20-negativo noto alla recidiva o alla progressione della malattia
• Precedente trapianto di cellule staminali (SCT) allogeniche
• Completamento di SCT autologhe nei 100 giorni precedenti il giorno 1 del ciclo 1
• Precedente terapia antitumorale standard o sperimentale
• Tossicità clinicamente significativa (diversa da alopecia) a causa della terapia precedente che non è migliorata al grado =2 (in base a NCI CTCAE v4.0) prima del giorno 1 del ciclo 1
• Linfoma follicolare di grado 3b
• Storia di trasformazione di malattia indolente in DLBCL
• Neuropatia periferica in corso di Grado >1
• Linfoma del SNC o infiltrazione leptomeningea
• Trattamento con corticosteroidi sistemici >20 mg/die di prednisone o farmaco equivalente
• Sensibilità o allergia nota a prodotti murini o a qualsiasi componente delle formulazioni di G, R, Pola o V.
• Evidenza di significative malattie concomitanti, non controllate in grado di influire sulla compliance con il protocollo o sull'interpretazione dei risultati
• Funzionalità ematologica inadeguata

E.5 End points

E.5.1

Primary end point(s)

Safety:
1. Incidence of dose limiting toxicities (DLTs) during Cycle 1 of study
Incidence of adverse events
3. Changes in vital signs, ECG and clinical laboratory results
Efficacy:
4. CR at EOI, as determined by the IRC through use of the PET-CT treatment

Sicurezza
1. incidenza delle tossicità dose limitanti (DLT) durante il primo ciclo del trattamento dello studio;
2. incidenza degli eventi avversi;
3. cambiamenti nei parametri vitali, nell'ECG e nei risultati degli esami clinici di laboratorio
Efficacia
4. CR all'EOI secondo quanto determinato dallo sperimentatore sulla base delle scansioni PET-TAC

E.5.1.1

Timepoint(s) of evaluation of this end point

1. From Day 1 (D1) to D28 of Cycle 1 (C1)
2. From screening up to 4.5 years
3. From screening up to 35 days after the last dose of maintenance/consolidation treatment
4. 6-8 weeks after Day 1 of the last induction cycle

1. dal giorno 1 (D1) AL D28 del ciclo 1 (C1)
2. dallo screening fino a 4.5 anni
3. dallo screening fino a 35 giorni dopo l'ultima dose di manteniment/consolidamento del trattamento.
6-8 settimane dopo il Day 1dell'ultimo ciclo di induzione

E.5.2

Secondary end point(s)

Efficacy:
1. CR at EOI, as determined by the Investigator on the basis of PET-CT scans
2. CR at EOI, as determined by the IRC and by the Investigator on the basis of CT scans alone
3. Objective response (defined as a CR or partial response [PR]) at EOI, as determined by the IRC and by the Investigator on the basis of PET-CT scans
4. Objective response (defined as a CR or PR) at EOI, as determined by the IRC and by the Investigator on the basis of CT scans alone
5. Best response of CR or PR during the study, as determined by the Investigator on the basis of CT scans alone
PK:
6. Observed serum Obi concentration at specified time points
7. Observed serum and plasma concentrations of Pola and its relevant analytes at specified time points
8. Observed serum concentration of R at specified time points
9. Observed plasma V concentration at specified time points
Immunogenicity
10. Incidence of human anti-human antibodies (HAHA) to G during the
study relative to the prevalence of HAHAs at baseline
11. Incidence of anti-therapeutic antibody (ATA) to Pola during the
study relative to the prevalence of ATAs, at baseline; Efficacy:
1. CR at EOI, as determined by the Investigator on the basis of PET-CT
scans
2. CR at EOI, as determined by the IRC and by the Investigator on the
basis of CT scans alone
3. Objective response (defined as a CR or partial response [PR]) at EOI,
as determined by the IRC and by the Investigator on the basis of PET-CT
scans
4. Objective response (defined as a CR or PR) at EOI, as determined by
the IRC and by the Investigator on the basis of CT scans alone
5. Best response of CR or PR during the study, as determined by the
Investigator on the basis of CT scans alone
PK:
6. Observed serum Obi concentration at specified time points
7. Observed serum and plasma concentrations of Pola and its relevant
analytes at specified time points
8. Observed plasma Ven concentration at specified time points
Immunogenicity
9. Incidence of human anti-human antibodies (HAHA) to Obi during the
study relative to the prevalence of HAHAs at baseline
10. Incidence of anti-therapeutic antibody (ATA) to Pola during the
study relative to the prevalence of ATAs, at baseline

1. CR all'EOI secondo quanto determinato dallo sperimentatore sulla base delle scansioni PET-TAC
2. CR all'EOI secondo quanto determinato dall'IRC sulla base delle TAC da sole
3. Risposta obiettiva [definita come una CR o una risposta parziale (PR)] all'EOI, come determinato dall'IRC e dallo sperimentatore sulla base delle scansioni PET-TAC
4. Risposta obiettiva (definita come una CR o PR) all'EOI, come determinato dall'IRC e dallo sperimentatore sulla base delle scansioni TAC da sole
5. Migliore risposta di CR o PR durante lo studio, come determinato dallo
sperimentatore sulla base delle scansioni TAC da sole.
PK
6. Concentrazione sierica di obinutuzumab G osservata in determinati momenti di valutazione,
7. Concentrazioni sieriche e plasmatiche di polatuzumab vedotin e analiti rilevanti osservate in determinati momenti di valutazione
8. Concentrazione sierica di R osservata in determinati momenti di valutazione
9. Concentrazione plasmatica di venetoclax osservata in determinati momenti di valutazione
10. Incidenza di anticorpi umani verso antigeni umani (HAHA) per obinutuzumab durante lo studio in relazione alla prevalenza di HAHA al momento iniziale
11. Incidenza di anticorpi anti-terapia (ATA) per polatuzumab vedotin durante lo studio in relazione alla prevalenza di ATA al momento iniziale; Efficacia:
1. CR all'EOI secondo quanto determinato dallo sperimentatore sulla base delle scansioni PET-TAC
2. CR all'EOI secondo quanto determinato dall'IRC sulla base delle TAC da sole
3. Risposta obiettiva [definita come una CR o una risposta parziale (PR)] all'EOI, come determinato dall'IRC e dallo sperimentatore sulla base delle scansioni PET-TAC
4. Risposta obiettiva (definita come una CR o PR) all'EOI, come determinato dall'IRC e dallo sperimentatore sulla base delle scansioni TAC da sole
5. Migliore risposta di CR o PR durante lo studio, come determinato dallo sperimentatore sulla base delle scansioni TAC da sole.
PK
6. Concentrazione sierica di obinutuzumab osservata in determinati momenti di valutazione,
7. Concentrazioni sieriche e plasmatiche di polatuzumab vedotin e analiti rilevanti osservate in determinati momenti di valutazione
8. Concentrazione plasmatica di venetoclax osservata in determinati momenti di valutazione
9. Incidenza di anticorpi umani verso antigeni umani (HAHA) per obinutuzumab durante lo studio in relazione alla prevalenza di HAHA al momento iniziale
10. Incidenza di anticorpi anti-terapia (ATA) per polatuzumab vedotin durante lo studio in relazione alla prevalenza di ATA al momento iniziale

E.5.2.1

Timepoint(s) of evaluation of this end point

Efficacy:
1-4. 6-8 weeks after Day 1 of the last induction cycle
5. Up to 4.5 years

PK:
6. Dose escalation phase (DP) and expansion phase (EP): C1D1, C2D1, C4D1, and C6D1; Maintenance phase (MP) and consolidation phase (CP): Month (M) 2D1, (M8D1, M14D1and M20D1 only for MP), at treatment discontinuation (TD), 120 days and 1 2 years after the last dose of Obi
7. DP and EP: C1D1, C1D8, C1D15, C2D1, C4D1, C6D1; MP and CP: at TD, 120 days and 1 2 years after the last dose of Pola
8. DP and EP: C1D1, C2D1, C4D1, C6D1

Immunogenicity:
9. DP and EP: on C1D1, C6D1; MP and CP: at TD, 120 days and 1 2 years after the last dose of Obi
10. DP and EP: C1D1, C2D1, C4D1; MP and CP: at TD, 120 days and 1 2 years after the last dose of Pola
; 1-4. 6-8 weeks after Day 1 of the last induction cy

1-4. 6-8 settimane dopo il giorno 1 dell'ultimo ciclo di induzione
5. fino a 4.5 anni
PK
6. Dose escalation phase (DP) and expansion phase (EP): C1D1, C2D1,C4D1, e C6D1; Fase di Mantemìnimento (MP) e fase di consolidamento (CP):
mesi (M) 2D1, (M8D1, M14D1e M20D1 solo MP), at treatment discontinuation (TD),
120 giorni e 1 2 anni dopo l'ultima dose di Obi.
7. DP and EP: C1D1, C1D8, C1D15, C2D1, C4D1, C6D1; MP and CP: at TD, 120 giorni e 1 / 2 anni dopo l'ultima dose di Pola
8 9. DP e EP: C1D1, C2D1, C4D1, C6D1
Immunogenicità
10. DP e EP: C1D1, C6D1; MP e CP: at TD, 120 giorni e 1/2 anni dall’ultima dose di Obi
11. DP e EP: C1D1, C2D1, C4D1; MP e CP: at TD, 120 giorni e 1/ 2 anni dall'ultima dose di Pola; 1-4. 6-8 settimane dopo il giorno 1 dell'ultimo ciclo di induzione
5. fino a 4.5 anni
PK

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

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

Yes

E.6.13.1

Other scope of the trial description

Immunogenicity

Immunogenicità

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

phase Ib

fase Ib

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)

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

United States

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 end of this study is defined as the time when both of the following criteria are met:
• All enrolled FL patients have completed or discontinued study treatment (including induction treatment and maintenance treatment as applicable).
• All enrolled DLBCL patients have been followed for at least 1 year after they have completed or discontinued study treatment

La fine dello studio è definita come il momento in cui vengono soddisfatti i seguenti criteri:
• Tutti i pazienti con FL arruolati hanno completato o interrotto il trattamento dello studio (compresi i trattamenti di induzione e di mantenimento, se pertinente)
• Tutti i pazienti arruolati con DLBCL sono stati seguiti per almeno 1 anno dopo aver completato o interrotto il trattamento dello studio (compresi i trattamenti di induzione e di consolidamento, se pertinente)

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

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial 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)

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.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

The Sponsor does not have any plans to provide obinutuzumab, polatuzumab vedotin, venetoclax, or any other study treatments or interventions to patients who have completed the study. The Sponsor will evaluate whether to continue providing obinutuzumab and polatuzumab vedotin in accordance with the Roche Global Policy on Continued Access to Investigational Medicinal Product, available at the following Web site:
http://www.roche.com/policy_continued_access_to_investigational_
medicines.pdf

Lo Sponsor non fornirà obinutuzumab, polatuzumab vedotin, venetoclax o altri trattamenti di studi o interventi su pazienti che hanno completato lo studio. Lo Sponsor valuterà se continuare a fornire obinutuzumab, polatuzumab vedotin, venetoclax in accordo laa policy di Roche Global sull'accesso continuato degli IMP disponibile sul sito: http://www.roche.com/policy_continued_access_to_investigational_
medicines.pdf

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

2016-03-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-12-11

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials