Clinical Trials Register

Summary
EudraCT Number:	2015-004729-15
Sponsor's Protocol Code Number:	IPI-145-21
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-06-09
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

Spain - AEMPS

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

Estudio de fase II, aleatorizado, de duvelisib administrado en combinación con rituximab frente a R-CHOP en pacientes con linfoma folicular recidivante o resistente al tratamiento

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.?

"Pacientes con Linfoma Folicular previamente tratados, que volverán a tratarse con una combinación de la medicación del estudio IPI-145 y Rituximab o la medicación para quimioterapia R-CHOP."

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	34911459110
B.5.6	E-mail	regulatory.spain@pharm-olam.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	IPI-145
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	5
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®
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 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.3.9.4	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	375
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: 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 injection/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.3.9.4	EV Substance Code	SUB06859MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	500 to 2000
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 injection/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.3.9.4	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®
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.3.9.4	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	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	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.IMP: 7
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	IPI-145
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.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 folicular recidivante o resistente al tratamiento

E.1.1.1

Medical condition in easily understood language

Worsened/resistant Follicular Lymphoma

Linfoma folicular empeorado o resistente al tratamiento

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	19.0
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

Yes

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.

Evaluar la eficacia de DR frente a R-CHOP en pacientes con LF recidivante o resistente al tratamiento

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

. Evaluar la seguridad de DR y de R-CHOP en pacientes con LF recidivante o resistente al tratamiento
. Caracterizar la farmacocinética (FC) de duvelisib cuando se administra con rituximab en pacientes con LF recidivante o resistente al tratamiento

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 < or =2 (corresponds to Karnofsky Performance Status [(KPS) > or = 60%])
7. For women of childbearing potential (WCBP): negative serum ? human chorionic gonadotropin (?hCG) 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)

1. Diagnóstico de LF: Grado 1, 2 o 3a
2. Los pacientes deben haber recibido rituximab, ya sea en monoterapia o como parte de alguna pauta combinada, y también deben cumplir uno de los siguientes requisitos (para mayor información véase el Apéndice 7):
a.Haber presentado progresión en los 24 meses posteriores al inicio de una pauta de quimioterapia que contenía un alquilante como tratamiento de primera línea y no haber recibido ningún otro tratamiento antineoplásico.
b.Haber presentado progresión en los 24 meses posteriores al inicio de una pauta de quimioterapia que contenía un alquilante como tratamiento de primera línea y, después, haber presentado progresión en los 24 meses posteriores a cualquier tratamiento de segunda línea y no haber recibido ningún otro tratamiento antineoplásico.
c.Haber presentado progresión en los 24 meses posteriores al inicio de una pauta de quimioterapia que contenía un alquilante como tratamiento de segunda línea y no haber recibido ningún otro tratamiento antineoplásico.
3. Recibido previamente Rituximab
4. Apto para recibir la pauta R-CHOP
5. Como mínimo una lesión patológica mensurable >1,5 cm en por lo menos una dimensión mediante tomografía computarizada (TC), TC/PET o resonancia magnética nuclear (RMN).
6. Estado funcional del Grupo Oncológico Cooperativo de la Costa Este de los Estados Unidos (Eastern Cooperative Oncology Group, ECOG) < o = 2 (corresponde a una puntuación > o = 60% en la escala del Estado Funcional de Karnofsky [EFK]).
7. Para mujeres con posibilidad de quedar embarazadas: prueba de embarazo en suero negativa para gonadotropina coriónica humana ? (?-hCG) en la semana anterior al primer tratamiento (una mujer con posibilidad de quedar embarazada se define como una mujer sexualmente madura que no se ha sometido a esterilización quirúrgica o que, en mujeres >55 años, no se encuentra en situación de posmenopausia natural durante un mínimo de 12 meses consecutivos).

E.4

Principal exclusion criteria

1. Clinical evidence of transformation to a more aggressive subtype of lymphoma or grade 3B FL
2. Received > or = 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

1. Signos clínicos de transformación a un subtipo de linfoma más agresivo o LF de grado 3B.
2. Haber recibido > o = 3 pautas de tratamiento antineoplásico antes de la inclusión.
3. Haber recibido quimioterapia R-CHOP previamente.
4. Haber recibido antraciclinas anteriormente.
5. Contraindicación de cualquiera de los componentes individuales de la pauta CHOP (ciclofosfamida, vincristina, doxorrubicina y prednisona). Reacción alérgica intensa o reacción anafiláctica a algún tratamiento con anticuerpos monoclonales o proteínas murinas o, hipersensibilidad conocida a alguno de los fármacos del estudio.
6. Haber recibido un alotrasplante previamente
7. Haber recibido tratamiento previo con un inhibidor de las fosfoinosítidos 3-cinasas (PI3K).
8. History of tuberculosis treatment within the two years prior to randomization
9. History of chronic liver disease, veno-occlusive disease, alcohol abuse
10.Tratamiento crónico, en curso, con inmunosupresores (p. ej., ciclosporina) o esteroides sistémicos a dosis >20 mg de prednisona (o equivalente) 1v/d.
11. Tratamiento en curso para infecciones bacterianas, fúngicas o víricas sistémicas en la selección o
12. Administración simultánea de medicamentos o alimentos que son inhibidores o inductores potentes del citocromo P450 3A (CYP3A).
13. Incapacidad para recibir tratamiento profiláctico para infecciones por Pneumocystis, el virus del herpes simple (VHS) o del herpes zóster (VHZ) en la selección.
14. Neoplasias malignas activas concurrentes, distintas del cáncer de piel no melanocítico, o carcinoma in situ de cuello uterino.
15. Antecedentes de accidente cerebrovascular, angina inestable, infarto de miocardio o arritmia ventricular que requieran medicación o marcapasos, en los 6 meses anteriores a la selección.

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

Supervivencia sin progresión (SSP), definida como el tiempo transcurrido desde la aleatorización hasta la confirmación de progresión de la enfermedad de acuerdo con los criterios modificados del Grupo de Trabajo Internacional (International Working Group, IWG) según la evaluación del Comité Revisor Independiente (CRI), o hasta la muerte por cualquier 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.

Tiempo transcurrido desde la aleatorización hasta la confirmación de progresión de la enfermedad, o muerte por cualquier cause, independientemente de lo que ocurra primero, evaluada hasta 39 meses

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)

. Tasa de respuesta completa (TRC), definiéndose la respuesta completa de acuerdo con los criterios modificados del IWG según la evaluación del CRI.
. Tasa de respuesta global (TRG), definiéndose la respuesta global como la mejor respuesta de respuesta completa (RC) o respuesta/remisión parcial (RP), de acuerdo con los criterios modificados del IWG según la evaluación del CRI.
. Supervivencia global (SG), definida como el tiempo transcurrido desde la aleatorización hasta la fecha de la muerte.
. Acontecimientos adversos (AA) y valores anormales de laboratorio.
. Parámetros FC de duvelisib e IPI-656 (metabolito principal).
. DdR, definida como el tiempo transcurrido desde la primera respuesta confirmada hasta la primera confirmación de progresión de la enfermedad (PE) de acuerdo con los criterios modificados del IWG o hasta la muerte por cualquier causa (únicamente para los pacientes con RC o RP)

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.

Los criterios de valoración secundarios serán evluados a lo largo del estudio, como evaluaciones llevadas a cabo. Los criterios de valoración se definen por acontecimientos adversos que pueden darse en cualquier 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

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

Austria

Belarus

Brazil

Bulgaria

Canada

Hungary

India

Israel

Italy

Mexico

Poland

Russian Federation

Serbia

Ukraine

United Kingdom

United States

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

Última visita del último paciente

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

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

Ninguno

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

2016-07-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-06-17

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

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Orphan Designation Number:
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