Clinical Trials Register

Summary
EudraCT Number:	2019-002217-19
Sponsor's Protocol Code Number:	M19-708
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2020-01-02
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2019-002217-19

A.3

Full title of the trial

Randomized, Open-label, 2-Arm, Multicenter, Phase 3 Study of Venetoclax and Azacitidine Versus Best Supportive Care as Maintenance Therapy for Patients with Acute Myeloid Leukemia in First Remission After Conventional Chemotherapy (VIALE-M)

A.3.1

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

Randomized, Open-label, 2-Arm, Multicenter, Study of Venetoclax and Azacitidine Versus Best Supportive Care as Maintenance Therapy for Patients with Acute Myeloid Leukemia in First Remission After Conventional Chemotherapy

A.4.1

Sponsor's protocol code number

M19-708

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	AbbVie Deutschland GmbH & Co. KG
B.1.3.4	Country	Germany
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	AbbVie 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	AbbVie Ltd.
B.5.2	Functional name of contact point	EU Clinical Trials Helpdesk
B.5.3	Address:
B.5.3.1	Street Address	Abbvie House, Vanwall Business Park
B.5.3.2	Town/ city	Maidenhead, Berkshire
B.5.3.3	Post code	SL6 4UB
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+441628561090
B.5.5	Fax number	+441628461153
B.5.6	E-mail	eu-clinical-trials@abbvie.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	EU/3/16/1767
D.3 Description of the IMP
D.3.1	Product name	Venetoclax
D.3.2	Product code	ABT-199 (GDC-0199)
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Venetoclax 10 mg
D.3.9.2	Current sponsor code	ABT-199 (GDC-0199)
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	Yes
D.2.5.1	Orphan drug designation number	EU/3/16/1767
D.3 Description of the IMP
D.3.1	Product name	Venetoclax
D.3.2	Product code	ABT-199 (GDC-0199)
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Venetoclax 50 mg
D.3.9.2	Current sponsor code	ABT-199 (GDC-0199)
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.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/16/1767
D.3 Description of the IMP
D.3.1	Product name	Venetoclax
D.3.2	Product code	ABT-199 (GDC-0199)
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Venetoclax 100 mg
D.3.9.2	Current sponsor code	ABT-199 (GDC-0199)
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: 4
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Vidaza®
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Europe Ltd
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Azacitidine
D.3.2	Product code	n/a
D.3.4	Pharmaceutical form	Powder for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Azacitidine
D.3.9.1	CAS number	320-67-2
D.3.9.2	Current sponsor code	n/a
D.3.9.3	Other descriptive name	Vidaza
D.3.9.4	EV Substance Code	SUB05624MIG
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

Acute Myeloid Leukemia (AML)

E.1.1.1

Medical condition in easily understood language

Hematologic Malignancies

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Part I: To determine the recommended Phase 3 dose of venetoclax in combination with AZA as maintenance therapy in subjects with AML who have achieved CR or CRi with conventional chemotherapy

Part II: To evaluate if venetoclax in combination with AZA as maintenance therapy improves relapse-free survival (RFS) comparing to BSC in subjects with AML who have achieved CR + CRi with conventional chemotherapy.

E.2.2

Secondary objectives of the trial

•To evaluate if venetoclax in combination with AZA as maintenance therapy improves overall survival (OS) in comparison to BSC
•To evaluate the safety of venetoclax in combination with AZA as maintenance therapy in comparison to BSC
•To evaluate if venetoclax in combination with AZA as maintenance therapy improves the MRD conversion rate among subjects who are MRD-positive at study initiation in comparison to BSC
•To evaluate if venetoclax in combination with AZA as maintenance therapy compared to BSC delays time to deterioration in Global Health Status (GHS)/(QoL) score as measured by procedures outlined in the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire - Core 30 item (EORTC QLQ C30) scoring manual
•To evaluate if venetoclax in combination with AZA as maintenance therapy has impact on fatigue when compared to BSC based on PRO assessment of the Patient Reported Outcomes Measurement Information System(PROMIS)Fatigue Short Form (SF) 7a

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subject must be ≥ 18 years old, have newly diagnosed AML with intermediate or adverse risk cytogenetics, have confirmed CR or CRi following completion of planned induction and consolidation chemotherapy, have achieved first CR + CRi within 4 months of enrollment or no more than 75 days since last dose of conventional chemotherapy, and have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
The key laboratory requirements are as follows:
•creatinine clearance ≥ 30 mL/minute; calculated by the Cockcroft Gault formula or measured by 24-hour urine collection;
•bilirubin < 3.0 × upper limit of normal (ULN) (adequate liver function);
•absolute neutrophil count ≥ 1,500/µL;
platelets ≥ 100,000/mm3.

E.4

Principal exclusion criteria

History of APL.
History of active central nervous system involvement with AML.

E.5 End points

E.5.1

Primary end point(s)

Part I: The primary endpoint is dose-limiting toxicities of venetoclax in combination with AZA

Part II:Relapse-Free Survival (RFS)

E.5.1.1

Timepoint(s) of evaluation of this end point

Timepoint for part I: After approximately 20 subjects have been treated for at least 28 days

Timepoint for part II: The time from randomization to the date of relapse or the date of death from any cause, whichever comes first.

E.5.2

Secondary end point(s)

•Overall Survival: OS is defined as the number of days from the date of randomization to the date of death.
•Minimal Residual Disease: The MRD conversion rate is defined as the proportion of subjects deemed MRD positive (≥ 10-3) at study initiation who converted to MRD of < 10-3 in the bone marrow after randomization or initiation of treatment.
•Patient-Reported Outcomes: GHS/QoL scale from the EORTC QLQ-C30 scores will be assessed and computed according to procedures outlined in EORTC QLQ-C30 scoring manual. Time to deterioration in GHS/QoL is defined as time from randomization to death from any cause or first-time decrease of ≥ 5 points from baseline.
•Patient-Reported Outcomes: Fatigue will be assessed using the PROMIS Fatigue SF 7a global fatigue score and calculated according to the procedure outlined in the PROMIS fatigue scoring manual. The impact on fatigue score will be evaluated by the change from baseline at all scheduled visits.

E.5.2.1

Timepoint(s) of evaluation of this end point

•Overall Survival: OS is defined as the number of days from the date of randomization to the date of death.
•The MRD conversion rate is defined as the proportion of subjects deemed MRD positive (≥ 10-3) at study initiation who converted to MRD of < 10-3 in the bone marrow after randomization or initiation of treatment.
•Time to deterioration in GHS/QoL is defined as time from randomization to death from any cause or first-time decrease of ≥ 5 points from baseline.
•The impact on fatigue score will be evaluated by the change from baseline at all scheduled visits."

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

Yes

E.6.10

Pharmacogenetic

Yes

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)

Yes

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

Best Supportive Care (BSC)

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

Australia

Brazil

Canada

China

Czech Republic

France

Germany

Greece

Hungary

Italy

Japan

Korea, Republic of

Russian Federation

Spain

Taiwan

Turkey

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

The end-of-study is defined as the date of the last subject's last visit or date of the last follow-up contact, whichever is later.

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:

160

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

200

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

117

F.4.2.2

In the whole clinical trial

360

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)

If a subject prematurely discontinues the study (withdrawal of informed consent), the procedures outlined for the final visit are to be completed as soon as possible, preferably within 2 weeks. In addition, if subject is willing, a 30-day follow-up phone call after the last dose of study drug for subjects in Part 1 and Part 2, Arm A or after study withdrawal for subjects in Part 2, Arm B may be completed to ensure all treatment-emergent AEs/SAEs have been resolved.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	NIHR Clinical Research Network Portfolio

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-12-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-04-29

P. End of Trial
P.	End of Trial Status	GB - no longer in EU/EEA

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

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

Clinical trials