Clinical Trials Register

Summary
EudraCT Number:	2015-004729-15
Sponsor's Protocol Code Number:	IPI-145-21
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2021-01-21
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

2015-004729-15

A.3

Full title of the trial

A Phase 2, Randomized Study of Duvelisib Administered in Combination with Rituximab vs R-CHOP in Subjects with Relapsed/Refractory Follicular Lymphoma

A Phase 2, Randomized Study of Duvelisib Administered in Combination
with Rituximab vs R-CHOP in Subjects with Relapsed/Refractory Follicular
Lymphoma

A.3.1

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

¿Subjects with previously treated Follicular Lymphoma who will be re-treated with a combination of the Study Drug IPI-145 and Rituximab or the chemo drug R-CHOP.¿

"I soggetti con linfoma follicolare precedentemente trattato che verranno ri-trattati con una combinazione del medicinale in studio IPI-145 e Rituximab o la chemio farmaco R-CHOP."

A.3.2

Name or abbreviated title of the trial where available

¿Subjects with previously treated Follicular Lymphoma who will be re-treated with a combination of t

"I soggetti con linfoma follicolare precedentemente trattati che verranno ri-trattati con una combi

A.4.1

Sponsor's protocol code number

IPI-145-21

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02605694

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	INFINITY PHARMACEUTICALS, INC.
B.1.3.4	Country	United States
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	Infinity Pharmaceuticals, Inc.
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	Infinity Pharmaceuticals, Inc.
B.5.2	Functional name of contact point	Mary Kuskin
B.5.3	Address:
B.5.3.1	Street Address	784 Memorial Drive
B.5.3.2	Town/ city	Cambridge, MA
B.5.3.3	Post code	02139
B.5.3.4	Country	United States
B.5.4	Telephone number	16174531394
B.5.5	Fax number	0016176821001
B.5.6	E-mail	Georgia.Christoforou@infi.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	Yes
D.2.5.1	Orphan drug designation number	EMA/OD/047/13
D.3 Description of the IMP
D.3.1	Product name	Duvelisib
D.3.2	Product code	IPI-145
D.3.4	Pharmaceutical form	Capsule, hard
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	duvelisib
D.3.9.1	CAS number	1386861-49-9
D.3.9.2	Current sponsor code	IPI-145
D.3.9.3	Other descriptive name	duvelisib
D.3.9.4	EV Substance Code	SUB62340
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	25
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	MabThera¿ 100 MG
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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 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	RITUXIMAB
D.3.9.1	CAS number	174722-31-7
D.3.9.2	Current sponsor code	RITUXIMAB
D.3.9.4	EV Substance Code	SUB12570MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
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)	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.IMP: 3
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	Endoxan ¿, Cytoxan¿, Neosar¿, Procytox¿, Revimmune¿, Cycloblastin¿
D.2.1.1.2	Name of the Marketing Authorisation holder	Baxter Oncology GmbH
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Cyclophosphamide
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	CYCLOPHOSPHAMIDE
D.3.9.1	CAS number	50-18-0
D.3.9.2	Current sponsor code	CYCLOPHOSPHAMIDE
D.3.9.3	Other descriptive name	CYCLOPHOSPHAMIDE
D.3.9.4	EV Substance Code	SUB06859MIG
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	20
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: 4
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	Adriamycin¿, Doxil¿, Myocet¿
D.2.1.1.2	Name of the Marketing Authorisation holder	Accord HealthCare Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Doxorubicin
D.3.4	Pharmaceutical form	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	DOXORUBICIN
D.3.9.1	CAS number	23214-92-8
D.3.9.2	Current sponsor code	DOXORUBICIN
D.3.9.3	Other descriptive name	DOXORUBICIN
D.3.9.4	EV Substance Code	SUB06391MIG
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	2
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: 5
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	Oncovin¿, Onco-tain¿
D.2.1.1.2	Name of the Marketing Authorisation holder	Hospira UK
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Vincristine
D.3.4	Pharmaceutical form	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	VINCRISTINE
D.3.9.1	CAS number	57-22-7
D.3.9.2	Current sponsor code	VINCRISTINE
D.3.9.3	Other descriptive name	VINCRISTINE
D.3.9.4	EV Substance Code	SUB00059MIG
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	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.IMP: 6
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	Prednisone
D.2.1.1.2	Name of the Marketing Authorisation holder	Hexal AG
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Lozenge
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	PREDNISONE
D.3.9.1	CAS number	57-22-7
D.3.9.2	Current sponsor code	PREDNISONE
D.3.9.3	Other descriptive name	PREDNISONE
D.3.9.4	EV Substance Code	SUB10020MIG
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	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

Relapsed/Refractory Follicular Lymphoma

Linfoma follicolare recidivante/refrattario

E.1.1.1

Medical condition in easily understood language

Worsened/resistant Follicular Lymphoma

Peggiorato /resistente linfoma follicolare

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	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10029473
E.1.2	Term	Nodular (follicular) lymphoma
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

The primary objective of this study is to evaluate the efficacy of DR vs R-CHOP in subjects with relapsed/refractory FL.

Obiettivo primario
¿ Valutare l'efficacia di DR rispetto a R-CHOP nei soggetti con LF
recidivante/refrattario

E.2.2

Secondary objectives of the trial

¿ Evaluate the safety of DR and R-CHOP in subjects with relapsed/refractory FL

¿ Characterize the pharmacokinetics (PK) of duvelisib when administered with rituximab in subjects with relapsed/refractory FL

Obiettivi secondari
¿ Valutare la sicurezza di DR rispetto a R-CHOP nei soggetti con LF
recidivante/refrattario
¿ Caratterizzare la farmacocinetica (PK) di duvelisib somministrato con rituximab in
soggetti affetti da LF recidivante/refrattario.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Diagnosis of FL: Grade 1, 2, or 3a
2. Subjects must have received rituximab, either as single agent or as part of any combination regimen, and also meet one of the following requirements (see Appendix 7 for more details):
a. Progressed within 24 months of initiating alkylator-based chemotherapy in the first line and received no additional anticancer therapy
b. Progressed within 24 months of initiating alkylator-based chemotherapy in the first line and subsequently progressed within 24 months of receiving any second-line treatment and received no additional anticancer therapy
c. Progressed within 24 months of initiating alkylator-based chemotherapy in the second line and received no additional anticancer therapy

3. Previously received rituximab
4. Appropriate to receive R-CHOP
5. At least 1 measurable disease lesion > 1.5 cm in at least one dimension by computed tomography (CT), CT-PET, or magnetic resonance imaging (MRI)
6. Eastern Cooperative Oncology Group (ECOG) performance status =2 (corresponds to Karnofsky Performance Status [(KPS) =60%])
7. For women of childbearing potential (WCBP): negative serum ß human chorionic gonadotropin (ßhCG) pregnancy test within 1 week before first treatment (WCBP defined as a sexually mature woman who has not undergone surgical sterilization or who has not been naturally post-menopausal for at least 12 consecutive months for women >55 years of age)

I soggetti possono essere eleggibili per l'inclusione nello studio se soddisfano i seguenti criteri:
1. = 18 anni di età
2. Diagnosi di LF: Grado 1, 2, o 3a
3. I soggetti devono aver ricevuto rituximab, o come agente singolo o nell'ambito di
qualsiasi regime di combinazione e devono soddisfare anche uno dei seguenti
requisiti (consultare l'Appendice 7 per ulteriori dettagli):
a. Progressione entro 24 mesi dall'inizio di chemioterapia di prima linea a base di
agente alchilante e nessun trattamento con terapia antitumorale aggiuntiva
b. Progressione entro 24 mesi dall'inizio di chemioterapia di prima linea a base di
agente alchilante e successiva progressione entro 24 mesi da qualsiasi trattamento
di seconda linea e nessun trattamento con terapia antitumorale aggiuntiva
c. Progressione entro 24 mesi dall'inizio di chemioterapia di seconda linea a base
di agente alchilante e nessun trattamento con terapia antitumorale aggiuntiva
Nota: La terapia a base di clorambucile come agente singolo non rientra nel requisito
di terapia con agente alchilante; i soggetti devono aver ricevuto almeno due cicli di
chemioterapia a base di agente alchilante per essere eleggibili
4. Idoneo/a a ricevere R-CHOP
5. Almeno 1 lesione della malattia misurabile > 1,5 cm in almeno una dimensione
rilevata mediante tomografia computerizzata (TAC), PET-TAC o risonanza
magnetica per immagini (RMI)
6. Devono presentare i seguenti parametri di laboratorio:
a. Conta assoluta dei neutrofili (ANC) = 1,0 x 109/l
b. Conta piastrinica = 75 x 109/l
c. Clearance della creatinina stimata in base alla formula di Cockcroft Gault =
30 ml/min
d. Bilirubina totale = 1,2 x il limite superiore della norma (ULN) (nel caso dei
soggetti affetti da Sindrome di Gilbert i valori di bilirubina possono essere
pari a > 1,5 × ULN, in conformità a quanto concordato tra lo sperimentatore
e il responsabile medico di Infinity)
e. AST/SGOT e ALT/SGPT =3,0 x ULN
7. Stato di performance ECOG (Eastern Cooperative Oncology Group) = 2
(corrispondente a uno stato di performance secondo Karnofsky [(KPS)
= 60%])
8. Per le donne in età fertile (WCBP): test di gravidanza negativo per la subunità ß della
gonadotropina corionica umana (ß-hCG) nel siero 1 settimana prima del primo
trattamento (per WCBP si intende una donna sessualmente matura che non abbia
subito sterilizzazione chirurgica o che non sia naturalmente in postmenopausa da
almeno 12 mesi consecutivi per le donne di età > 55 anni)
9. Disponibilità di soggetti di sesso maschile e femminile non chirurgicamente sterili
o postmenopausali a usare metodi contraccettivi clinicamente accettabili per la
Protocollo IPI-145-
21 Duvelisib (IPI-
145)
Infinity Pharmaceuticals, Inc.
05 Febbraio 2016 (Emendamento 1) RISERVATO Pagina 10 di 89
durata del trattamento in studio inclusi 30 giorni dopo l'ultima dose di duvelisib, 12
mesi dopo l'ultima dose di R in monoterapia o di R-CHOP
10. Modulo di consenso informato approvato dall'Institutional Review Board
(IRB)/Comitato etico indipendente (CEI) firmato e datato prima dell'esecuzione di
qualsiasi procedura di screening

E.4

Principal exclusion criteria

1. Clinical evidence of transformation to a more aggressive subtype of lymphoma or grade 3B FL
2. Received = 3 previous anticancer regimens prior to enrollment
3. Received prior R-CHOP therapy
4. Previous receipt of any anthracycline
5. Contraindication to any of the individual components of CHOP (cyclophosphamide, vincristine, doxorubicin and prednisone) Severe allergic or anaphylactic reaction to any monoclonal antibody therapy, murine protein, or known hypersensitivity to any of the study drugs
6. Received prior allogeneic transplant
7. Received prior treatment with a phosphoinositide-3-kinase (PI3K) inhibitor
8. History of tuberculosis treatment within the two years prior to randomization
9. History of chronic liver disease, veno-occlusive disease, alcohol abuse
10. Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine) or systemic steroids >20 mg of prednisone (or equivalent) QD
11. Ongoing treatment for systemic bacterial, fungal, or viral infection at screening antifungal, or
12. Concurrent administration of medications or foods that are strong inhibitors or inducers of cytochrome P450 3A (CYP3A)
13. Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), or herpes zoster (VZV) at screening
14. Concurrent active malignancy other than nonmelanoma skin cancer, carcinoma in situ of the cervix.
15. History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or a pacemaker within the last 6 months prior to screening

I soggetti devono essere esclusi dallo studio se soddisfano uno qualsiasi dei seguenti criteri:
1. Evidenza clinica di trasformazione in un sottotipo di linfoma più aggressivo o LF di
grado 3B
2. = 3 precedenti regimi di trattamento antitumorale ricevuti prima
dell'arruolamento
3. Terapia a base di R-CHOP ricevuta in precedenza
4. Trattamento precedente con qualsiasi antraciclina
5. Controindicazioni per uno qualsiasi dei singoli componenti di CHOP
(ciclofosfamide, vincristina, doxorubicina e prednisone)
6. Reazione allergica grave o anafilattica a qualsiasi terapia con anticorpi
monoclonali, proteina murina o ipersensibilità nota a uno dei farmaci in studio
7. Trapianto allogenico ricevuto in precedenza
8. Trattamento con un inibitore di fosfoinositide-3-chinasi (PI3K) ricevuto in precedenza
9. Intervento chirurgico importante nelle 4 settimane precedenti lo screening
10. Uso di chemioterapia, radioterapia, terapia ablativa midollare o qualsiasi terapia
sperimentale entro 4 settimane dalla randomizzazione
11. NHL che coinvolge il sistema nervoso centrale (SNC); non è richiesta puntura
lombare a meno che sussista il sospetto clinico di coinvolgimento del SNC
12. Infezione da epatite B, epatite C o virus dell'immunodeficienza umana (HIV)
13. Anamnesi di trattamento per la tubercolosi entro i due anni prima della
randomizzazione
14. Anamnesi di patologia epatica cronica, patologia veno-occlusiva, abuso di alcol
15. I soggetti trattati in precedenza con lenalidomide devono aver completato il
trattamento 6 settimane prima della randomizzazione
16. Trattamento in corso con uso cronico di immunosoppressori (per es. ciclosporina)
o steroidi sistemici > 20 mg di prednisone (o equivalente) QD (al giorno)
17. Trattamento in corso per infezione sistemica batterica, fungina o virale al momento
dello screening
NOTA: I soggetti in profilassi antimicrobica, antifungina o antivirale non sono
esclusi in modo specifico se soddisfano tutti gli altri criteri di inclusione/esclusione
18. Somministrazione di un vaccino vivo entro 6 settimane prima della
randomizzazione
19. Somministrazione concomitante di farmaci o alimenti che siano forti inibitori o
induttori del citocromo P450 3A (CYP3A)
20. Impossibilità di ricevere il trattamento profilattico per pneumocisti, virus herpes
simplex (HSV) e il virus varicella zoster (VZV) allo screening
21. Frazione di eiezione ventricolare sinistra alla baseline (LVEF) < 45%
Protocollo IPI-145-
21 Duvelisib (IPI-
145)
Infinity Pharmaceuticals, Inc.
05 Febbraio 2016 (Emendamento 1) RISERVATO Pagina 12 di 89
22. Intervallo QT corretto con il metodo Fridericia (QTcF) alla baseline > 480 ms
NOTA: il criterio non si applica a soggetti con blocco di branca (BB) destra o
sinistra
23. Precedente intervento chirurgico o disfunzione gastrointestinale che possa influire
sull'assorbimento dei farmaci (ad es. intervento chirurgico di bypass gastrico,
gastrectomia)
24. Soggetti di sesso femminile in gravidanza o allattamento
25. Tumore maligno attivo concomitante diverso da carcinoma cutaneo non
melanomatoso, carcinoma della cervice in situ
NOTA: I soggetti colpiti in precedenza da tumori maligni sono eleggibili se liberi da
malattia da >2 anni.
26. Anamnesi di ictus, angina instabile, infarto miocardico a aritmia ventricolare che abbia
richiesto trattamento medico o pacemaker entro gli ultimi 6 mesi prima dello screening
27. Malattia instabile o malattia grave non controllata (ad es. funzione cardiaca instabile,
malattia polmonare instabile, diabete non controllato) o qualsiasi altra patologia
importante o risultato anomalo di esami di laboratorio che, secondo il giudizio dello
sperimentatore, potrebbe aumentare i rischi per il paziente in conseguenza della sua
partecipazione allo studio

E.5 End points

E.5.1

Primary end point(s)

Progression Free Survival (PFS), defined as the time from randomization
to documented disease progression according to the revised
International Working Group (IWG) criteria as assessed by the
Independent Review Committee (IRC), or death due to any cause

Sopravvivenza libera da progressione (PFS), definita come il tempo dalla
randomizzazione alla progressione documentata della malattia secondo i criteri
rivisti dell'International Working Group (IWG) valutata dal Comitato di revisione
indipendente (IRC), o decesso per qualsiasi causa

E.5.1.1

Timepoint(s) of evaluation of this end point

Time from randomization to documented disease progression, or death
due to any cause, whatever comes first, assessed up to 39 months.

Tempo dalla randomizzazione alla progressione della malattia documentata, o la morte dovuta a qualsiasi causa, indipendentemente da quale si manifesti prima, valutata fino a 39 mesi.

E.5.2

Secondary end point(s)

Complete Response Rate (CRR), with complete response defined
according to the revised IWG criteria as assessed by the IRC
¿ Overall Response Rate (ORR), with overall response defined as best
response of complete response (CR) or partial response/remission (PR), according to the revised IWG criteria as assessed by the IRC
¿ Overall Survival (OS), defined as the time from randomization to the
date of death
¿ Adverse events (AEs) and abnormal laboratory values.
¿ PK parameters for duvelisib and IPI-656 (major metabolite)
¿ DOR defined as the time from the first documented response to the
first documentation of progressive disease (PD) according to the revised
IWG criteria or death due to any cause (for subjects with CR or PR only)

Tasso di risposta completa (CRR), con risposta completa definita in base ai criteri
rivisti dell'IWG, valutata dall'IRC
¿ Tasso di risposta globale (ORR), con risposta globale definita come migliore
risposta completa (CR) o risposta/remissione parziale (PR), secondo i criteri
rivisti dell'IWG, valutata dall'IRC.
¿ Sopravvivenza globale (OS), definita come il tempo dalla data della
randomizzazione alla data del decesso
¿ Eventi avversi (EA) e valori di laboratorio anomali
¿ Parametri PK per duvelisib e IPI-656 (metabolita principale)
¿ Durata della Risposta (DOR) definita come il tempo dalla prima risposta
documentata alla prima documentazione di malattia progressiva (PD) in base ai
criteri IWG rivisti o decesso per qualsiasi causa (solo per soggetti che evidenziano
CR o PR)

E.5.2.1

Timepoint(s) of evaluation of this end point

The secondary end points will be evaluated throughout the study, as
assesments are done. End points defined by adverse events can be
reached at any time.

Gli end-point secondari saranno valutati durante il corso dello studio. Gli end-point definiti da eventi avversi possono essere raggiunti in qualsiasi momento.

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

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

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

Yes

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)

Yes

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

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

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

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:

100

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

100

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

115

F.4.2.2

In the whole clinical trial

230

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

2016-06-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-07-12

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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Orphan Designation Number:
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