Clinical Trials Register

Summary
EudraCT Number:	2015-002892-30
Sponsor's Protocol Code Number:	1315.2
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2017-04-10
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

2015-002892-30

A.3

Full title of the trial

An open-label, Phase I/II trial to determine the maximum tolerated dose and investigate safety, pharmacokinetics and efficacy of BI 836858 in combination with decitabine in patients with acute myeloid leukemia

Ensayo abierto de Fase I/II para determinar la dosis máxima tolerada y evaluar la seguridad, la farmacocinética y la eficacia de BI 836858 en combinación con decitabina en pacientes con leucemia mieloide aguda

A.3.1

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

A study to find and investigate a safe dose of BI 836858 in combination with decitabine for patients with acute myeloid leukemia (AML)

Un ensayo para encontrar e investigar una dosis segura de BI 836858 en combinación con decitabina en pacientes con leucemia mieloide aguda (LMA)

A.4.1

Sponsor's protocol code number

1315.2

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	Boehringer Ingelheim España, 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	Boehringer Ingelheim España, S.A.
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Boehringer Ingelheim Pharma GmbH & Co. KG
B.5.2	Functional name of contact point	QRPE PSC CT Information Disclosure
B.5.3	Address:
B.5.3.1	Street Address	Binger Strasse 173
B.5.3.2	Town/ city	Ingelheim am Rhein
B.5.3.3	Post code	55216
B.5.3.4	Country	Germany
B.5.4	Telephone number	+3493404 5100
B.5.5	Fax number	+3493404 5580
B.5.6	E-mail	clintriage.rdg@boehringer-ingelheim.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	BI 836858
D.3.2	Product code	-
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	-
D.3.9.1	CAS number	-
D.3.9.2	Current sponsor code	BI 836858
D.3.9.3	Other descriptive name	CD33 MONOCLONAL ANTIBODIES
D.3.9.4	EV Substance Code	SUB129677
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	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

patients with acute myeloid leukemia

pacientes con leucemia mieloide aguda

E.1.1.1

Medical condition in easily understood language

patients with acute myeloid leukemia (AML), a type of cancer of the blood and bone marrow

pacientes con leucemia mieloide aguda (LMA), un tipo de cáncer de la sangre y la médula ósea

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	19.1
E.1.2	Level	LLT
E.1.2	Classification code	10000886
E.1.2	Term	Acute myeloid leukemia
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

Phase I Dose Escalation:
To determine the maximum tolerated dose (MTD) and the recommended dose for Phase I Extension and to investigate the safety, pharmacokinetics (PK) and efficacy of BI 836858 in combination with decitabine in patients >/= 65 years of age with previously untreated acute myeloid leukemia (AML) and considered ineligible for standard intensive therapy, or patients >/= 18 years of age with refractory or relapsed AML.
Phase I Extension:
To collect additional data on safety, PK and efficacy and to define the Recommended Phase II Dose (RP2D) of BI 836858 in combination with decitabine in patients >/= 65 years of age with previously untreated AML and considered ineligible for standard intensive therapy.
Phase II:
To investigate efficacy, safety and PK of BI 836858 in combination with decitabine compared to decitabine monotherapy in patients >/= 65 years of age with previously untreated AML and considered ineligible for standard intensive therapy.

Fase I de aumento progresivo de la dosis:Determinar dosis máxima tolerada(DMT) y dosis recomendada para Fase I de ampliación y evaluar seguridad,farmacocinética(PK) y eficacia de BI 836858 en combinación con decitabina en pacientes >/=65 años con LMA no tratada previamente y que no cumplen los requisitos para recibir el tratamiento intensivo de referencia,o pacientes >/=18 años con LMA recidivante o resistente al tratamiento.
Fase I de ampliación:Obtener datos adicionales de seguridad,PK y eficacia y definir Dosis Recomendada para Fase II(DRF2)de BI 836858 en combinación con decitabina en pacientes >/=65 años con LMA no tratada previamente y que no cumplen los requisitos para recibir el tratamiento intensivo de referencia.
Fase II:Evaluar eficacia,seguridad y PK de BI 836858 en combinación con decitabina en comparación con decitabina en monoterapia en pacientes >/=65 años con LMA no tratada previamente y que no cumplen requisitos para recibir el tratamiento intensivo de referencia.

E.2.2

Secondary objectives of the trial

The secondary endpoint of the Phase I part of this trial is objective response (Complete Remission/ Complete Remission with incomplete blood count recovery).
Secondary endpoints of the Phase II part of this trial are Event-free survival (EFS), Relapse-free survival (RFS), Remission duration and Time to remission.

El criterio secundario de valoración de la Fase I de este ensayo es la respuesta objetiva (Remisión Completa/ Remisión Completa con recuperación hematológica incompleta).
Criterios secundarios de valoración de la Fase II de este ensayo son Supervivencia sin acontecimientos (EFS), Supervivencia libre de recaídas (RFS), Duración de la remisión y Tiempo hasta la remisión.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1)Phase I Dose Escalation:
a.Male or female patients >/= 18 years of age with relapsed or refractory AML
b.Male or female patients >/= 65 years of age with previously untreated AML ineligible for receiving standard intensive therapy

Phase I Extension and Phase II:
Male or female patients >/= 65 years of age with previously untreated AML ineligible for receiving standard intensive therapy

2)Histologically or cytologically confirmed AML according to the WHO classification
3)Patients must be eligible for treatment with decitabine
4)Eastern co-operative oncology group (ECOG) performance score </=2 at screening

1) Fase I de aumento progresivo de la dosis:
a. Pacientes varones o mujeres >/= 18 años con LMA recidivante o resistente al tratamiento
b. Pacientes varones o mujeres >/= 65 años con LMA no tratada previamente que no cumplen los requisitos para recibir el tratamiento intensivo de referencia

Fase I de ampliación y Fase II:
Pacientes varones o mujeres >/= 65 años con LMA no tratada previamente que no cumplen los requisitos para recibir el tratamiento intensivo de referencia

2) LMA confirmada histológica o citológicamente, de conformidad con la clasificación de la OMS
3) Pacientes que cumplen los requisitos para recibir tratamiento con decitabina
4) Puntuación </=2 en la escala de valoración Eastern Cooperative Oncology Group (ECOG) en el momento del cribado.

E.4

Principal exclusion criteria

1) Acute promyelocytic leukemia (APL, French-American-British (FAB) subtype M3), according to WHO classification
2) Patients who are candidates for allogeneic stem cell transplantation.
3) Active chronic graft versus host disease requiring immunosuppressive treatment
4) Prior treatment with a hypomethylating agent (this also includes prior MDS treatment with decitabine or azazitidine)
5) Prior treatment with Cluster of differentiation 33 (CD33) antibody

1) Leucemia promielocítica aguda (LPA, subtipo M3 según la clasificación franco-anglo-estadounidense (FAB)), de conformidad con la clasificación de la OMS
2) Pacientes que son candidatos para el trasplante alogénico de células madre
3) Enfermedad activa crónica de injerto contra huésped que requiere tratamiento inmunosupresor
4) Tratamiento previo con agente hipometilante (esto también incluye tratamiento previo del síndrome mielodisplásico con decitabina o azacitidina)
5) Tratamiento previo con anticuerpo anti-CD33 (grupo de diferenciación 33)

E.5 End points

E.5.1

Primary end point(s)

1: Phase I: MTD of BI 836858 in combination with decitabine

2: Phase I: Number of patients with dose limiting toxicity (DLT(s)) during first treatment cycle

3: Phase II:Number of patients with objective response combining
- Complete remission (CR)
- CR with incomplete blood count recovery (CRi)

1: Fase I: DMT de BI 836858 en combinación con decitabina

2: Fase I: Número de pacientes con toxicidad limitante de dosis (TLD(s)) durante el primer ciclo de tratamiento

3: Fase II: Número de pacientes con respuesta objetiva combinando
- Remisión completa (RC)
- RC con recuperación hematológica incompleta (RCi)

E.5.1.1

Timepoint(s) of evaluation of this end point

1: 12 months

2: 12 months

3: 30 months

1: 12 meses

2: 12 meses

3: 30 meses

E.5.2

Secondary end point(s)

1: Phase I: Number of patients with objective response combining
- Complete remission (CR)
- CR with incomplete blood count recovery (CRi)

2: Phase II:
- Event free survival (EFS)

3: Phase II:
- Relapse free survival (RFS)

4: Phase II:
- Remission duration

5: Phase II:
- Time to remission

1: Fase I: Número de pacientes con respuesta objetiva combinando
- Remisión completa (RC)
- RC con recuperación hematológica incompleta (RCi)

2: Fase II:
- Supervivencia sin acontecimientos (EFS)

3: Fase II:
- Supervivencia libre de recaídas (RFS)

4: Fase II:
- Duración de la remisión

5: Fase II:
- Tiempo hasta la remisión

E.5.2.1

Timepoint(s) of evaluation of this end point

1: 30 months

2: 30 months

3: 30 months

4: 30 months

5: 30 months

1: 30 meses

2: 30 meses

3: 30 meses

4: 30 meses

5: 30 meses

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

Yes

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)

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

Dose escalation and extension

Aumento progresivo de la dosis y ampliación

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Todos los pacientes serán tratados con decitabina como tratamiento estándar (quimioterapia de base)

All patients will receive treatment with decitabine as standard of care (backbone chemotherapy)

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

Belgium

France

Germany

Italy

Spain

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

The end of the trial will be defined as when the following have occurred:
1. All randomized patients have discontinued trial drug
2. The last patient has completed the EoR visit

El ensayo se considerará finalizado cuando lo siguiente haya ocurrido:
1. Todos los pacientes aleatorizados hayan discontinuado el tratamiento del ensayo
2. El último paciente haya completado la visita del fin del período de efecto residual

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

Number of subjects for this age range:

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:

145

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

150

F.4.2.2

In the whole clinical trial

200

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 patients will be treated according to local standard care by their investigators after they terminated the trial.

Los pacientes serán tratados por sus investigadores de acuerdo con el tratamiento estándar local una vez hayan finalizado el ensayo.

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

2017-07-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-06-16

P. End of Trial
P.	End of Trial Status	Ongoing

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