Clinical Trials Register

Summary
EudraCT Number:	2012-002208-41
Sponsor's Protocol Code Number:	CBKM120Z2402
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:	2013-01-25
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2012-002208-41

A.3

Full title of the trial

An open-label phase II study of BKM120 in patients with relapsed and refractory diffuse large B-cell lymphoma, mantle cell lymphoma and follicular lymphoma

Estudio fase II, abierto, de BKM120, en pacientes con linfoma B difuso de células grandes, linfoma de células del manto y linfoma folicular refractario o en recidiva

A.3.1

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

A Phase II study of BKM120 in patients with relapsed and refractory
diffuse large B-cell lymphoma, mantle cell lymphoma and follicular
lymphoma

Estudio fase II, abierto, de BKM120, en pacientes con linfoma B difuso de células grandes, linfoma de células del manto y linfoma folicular refractario o en recidiva

A.4.1

Sponsor's protocol code number

CBKM120Z2402

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	Novartis Farmacéutica S.A.
B.1.3.4	Country	Spain
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	Novartis Pharma Services AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Farmacéutica S.A.
B.5.2	Functional name of contact point	Departamento Médico Oncología (GMO)
B.5.3	Address:
B.5.3.1	Street Address	C/ Gran Via de les Corts Catalanes, 764
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08013
B.5.3.4	Country	Spain
B.5.4	Telephone number	34900353036
B.5.5	Fax number	34932479903
B.5.6	E-mail	eecc.novartis@novartis.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	BKM120
D.3.2	Product code	BKM120
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	buparlisib
D.3.9.1	CAS number	not known
D.3.9.2	Current sponsor code	BKM120
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	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	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	BKM120
D.3.2	Product code	BKM120
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	buparlisib
D.3.9.1	CAS number	not known
D.3.9.2	Current sponsor code	BKM120
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	50
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

Diffuse large B-cell lymphoma, Mantle cell lymphoma and Follicular
lymphoma

Linfoma B difuso de células grandes, linfoma de células del manto y linfoma folicular

E.1.1.1

Medical condition in easily understood language

Diffuse large B-cell lymphoma, Mantle cell lymphoma and Follicular
lymphoma

Linfoma B difuso de células grandes, linfoma de células del manto y linfoma folicular

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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10012822
E.1.2	Term	Diffuse large B-cell lymphoma refractory
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10026801
E.1.2	Term	Mantle cell lymphoma refractory
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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

To determine the efficacy of BKM120 in patients with relapsed/refractory Non-Hodgkin Lymphoma in the three different histological subgroups

Determinar la eficacia de BKM120 en pacientes con linfoma no Hodgkin refractario/en recidiva en los tres subgrupos histológicos distintos

E.2.2

Secondary objectives of the trial

To evaluate the safety and tolerability in the three different histological subgroups

To assess progression free survival in the three different histological subgroups

To assess the duration of response in the three different histological subgroups

To assess overall survival in the three different histological subgroups

Evaluar la seguridad y tolerabilidad en los tres subgrupos histológicos distintos
Evaluar la supervivencia libre de progresión en los tres subgrupos histológicos distintos
Evaluar la duración de la respuesta en los tres subgrupos histológicos distintos
Evaluar la supervivencia global en los tres subgrupos histológicos distintos

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Patient has a histologically confirmed diagnosis of mantle cell
lymphoma, follicular lymphoma, or diffuse large B cell lymphoma. 2.
Patient has relapsed or refractory disease and received at least one prior
therapy. 3. Patient with diffuse large B cell lymphoma has received or is
ineligible for autologous or allogeneic stem cell transplant. 4. Patient has
at least one measurable nodal lesion (?2 cm) according to Cheson
criteria (Cheson 2007). In case where the patient has no measurable
nodal lesions ? 2 cm in the long axis at baseline, then the patient must
have at least one measurable extra-nodal lesion. 5. Patient has an
Eastern Cooperative Oncology Group (ECOG) performance status ? 2. 6.
Patient has adequate bone marrow and organ function.

1 Pacientes con diagnóstico histológicamente confirmado de linfoma de células del manto, linfoma folicular o linfoma B difuso de células grandes
2. Pacientes con enfermedad refractaria o en recidiva y que hayan recibido por lo menos una terapia previa
3. Pacientes con linfoma B difuso de células grandes que hayan recibido o que no sean elegibles para trasplante de células madre alogénico o autólogo.
4. Paciente con por lo menos una lesión ganglionar medible (?2 cm) según los criterios de Cheson (Cheson 2007). En el caso de que el paciente presente lesiones ganglionares no medibles ? 2 cm en el eje más largo, en la visita basal, entones el paciente deberá presentar por lo menos una lesión extraganglionar medible
5. Paciente con estado funcional del Grupo Oncológico Cooperativo del Este (ECOG) ? 2

6. Pacientes con función orgánica y de la médula ósea adecuada .
También aplican otros criterios de inclusión definidos en el protocolo

E.4

Principal exclusion criteria

1. 1. Patient has received previous treatment with PI3K. 2. Patient has
evidence of graft versus host disease (GVHD). 3. Patient has active or
history of central nervous system (CNS) disease. 4. Patient has a
concurrent malignancy or has a malignancy within 3 years of study
enrollment (with the exception of adequately treated basal or squamous
cell carcinoma or non-melanomatous skin cancer). 5. Patient has a score
? 12 on the PHQ-9 questionnaire. 6. Patient has a GAD-7 mood scale
score ? 15. 7. Pregnant or nursing women and who does not use highly
effective contraception methods to avoid becoming pregnant or
conciving offspring. Other protocol-defined inclusion/exclusion criteria
may apply.

1. Pacientes que hayan recibido tratamiento previo con PI3K
2. Pacientes con evidencia de enfermedad del injerto contra el huésped (EICH)
3. Pacientes con antecedentes de o enfermedad del sistema nervioso central (SNC) activa
4. Pacientes con enfermedad maligna concurrente o con enfermedad activa dentro de los 3 años de la inclusión del estudio (con la excepción de carcinoma de células escamosas o basales o cáncer cutáneo no melanoma)
5. Pacientes con una puntuación ? 12 en el cuestionario PHQ-9
6.Pacientes con puntuación en la escala del estado de ánimo GAD-7 ? 15
7.Pacientes embarazadas o en periodo de lactancia, ,
Pacientes que no utilicen métodos anticonceptivos altamente eficaces durante el estudio y durante el periodo definido a continuación después de la dosis final del tratamiento del estudio
También aplican otros criterios de exclusión definidos en el protocolo.

E.5 End points

E.5.1

Primary end point(s)

- Objective Response rate (ORR)

- Tasa de respuesta objetiva (TRO)
-

E.5.1.1

Timepoint(s) of evaluation of this end point

up to 2 years when all cohorts are completed

Por encima de los 2 años, cuando todas las cohortes hayan finalizado.

E.5.2

Secondary end point(s)

Frequency and severity of adverse events; other safety data as
considered appropriate
PFS progression free survival
Duration of response
OS Overall survival.

Frecuencia y severidad de acontecimientos adversos; otros datos de seguridad, cuando se considere apropiado.
Supervivencia libre de progresión (SLP)
- Duración de la respuesta
- Supervivencia global (SG)

E.5.2.1

Timepoint(s) of evaluation of this end point

up to 2 years when all cohorts are completed

Por encima de los 2 años, cuando todas las cohortes hayan finalizado.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

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

Belgium

Brazil

France

Germany

Korea, Republic of

Spain

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 the trial will be when all patients in each cohort have
completed their 6 months assessment or discontinued early

El estudio finalizará cuando todos los pacientes de cada cohorte hayan completado los 6 meses de estudio o hayn discontinuado tempranamente

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

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)

After discontinuing study treatment, further treatment is left to the
physician's discretion.

Después de la discontinuación del tratamiento del estudio el médico decidirá los tratamientos posteriores.

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

2013-01-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-01-10

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

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