Clinical Trials Register

Summary
EudraCT Number:	2015-003667-11
Sponsor's Protocol Code Number:	M15-550
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-09-06
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2015-003667-11

A.3

Full title of the trial

Open-Label, Single Arm, Phase 3B, Multi-Center Study Evaluating the Efficacy of Venetoclax (ABT 199) in Relapsed/Refractory Subjects with Chronic Lymphocytic Leukemia (CLL) (VENICE I)

Sperimentazione Multicentrica di Fase 3b, in Aperto e Braccio Singolo per Valutare l’Efficacia di Venetoclax (ABT-199) in Soggetti con Leucemia Linfatica Cronica (CLL) Recidivante/Refrattaria. (VENICE I)

A.3.1

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

A study evaluating venetoclax (ABT-199) in subjects with Chronic Lymphocytic Leukemia (CLL) whose cancer has come back or who had no response to previous cancer treatments including subjects who may be missing part of their chromosome 17 identified as 17p deletion, or TP53 gene mutation; or subjects who previously received treatment with B-cell receptor inhibitors.

Sperimentazione per Valutare Venetoclax (ABT-199) in Soggetti con Leucemia Linfatica Cronica (CLL) il cui tumore è tornato indietro o non ha risposto al precedente trattamento con farmaci anti-cancro, compresi i Soggetti che potrebbero avere una parte mancante del loro cromosoma 17 identificata come Delezione del Cromosoma 17p o con Mutazione TP53 OPPURE i Soggetti che sono stati in precedenza trattati con inibitori del recettore dei linfociti B.

A.3.2

Name or abbreviated title of the trial where available

M15-550

A.4.1

Sponsor's protocol code number

M15-550

A.5.4

Other Identifiers

Name:

n.a

Number:

M15-550

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, Vanwall Road
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/3/12/1080
D.3 Description of the IMP
D.3.1	Product name	Venetoclax
D.3.2	Product code	[ABT-199]
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 10mg
D.3.9.2	Current sponsor code	ABT-199
D.3.9.4	EV Substance Code	SUB176260
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	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)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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/3/12/1080
D.3 Description of the IMP
D.3.1	Product name	Venetoclax
D.3.2	Product code	[ABT-199]
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 50mg
D.3.9.2	Current sponsor code	ABT-199
D.3.9.4	EV Substance Code	SUB176260
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	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)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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/3/12/1080
D.3 Description of the IMP
D.3.1	Product name	Venetoclax
D.3.2	Product code	[ABT-199]
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 100mg
D.3.9.2	Current sponsor code	ABT-199
D.3.9.4	EV Substance Code	SUB176260
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	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)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

Chronic Lymphocytic Leukemia

Leucemia Linfatica Cronica

E.1.1.1

Medical condition in easily understood language

Chronic lymphocytic leukemia (CLL) is a type of cancer affecting the blood and the bone marrow.

La Leucemia Linfatica Cronica (CLL) è un tipo di tumore che colpisce il sangue ed il midollo osseo.

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	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10008957
E.1.2	Term	Chronic lymphatic leukemia
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 to evaluate the efficacy of venetoclax monotherapy in subjects with relapsed or refractory chronic lymphocytic leukemia (CLL).

L’obiettivo primario di questa sperimentazione è la valutazione dell’efficacia di venetoclax in monoterapia in soggetti affetti da leucemia linfatica cronica (CLL) recidivante o refrattaria.

E.2.2

Secondary objectives of the trial

The secondary objectives are to evaluate other efficacy parameters including the overall response rate (ORR), duration of overall response (DoR), time to progression (TTP), progression-free survival (PFS), overall survival (OS), Complete Remission rate in BCRi treated subjects

Gli obiettivi secondari intendono valutare altri parametri di efficacia, fra cui il tasso di risposta globale (overall response rate, ORR), la durata della risposta globale (duration of response, DoR), il tempo alla progressione (time to progression, TTP), la sopravvivenza libera da progressione (progression-free survival, PFS), la sopravvivenza globale (overall survival, OS), il tasso di CR nei soggetti con pregresso trattamento con BCRi

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age = 18 years.
2. Eastern Cooperative Oncology Group (ECOG) performance score of = 2.
3. Subject has relapsed/refractory disease (received at least one line of prior therapy).
4. Diagnosis of CLL that meets published 2008 Modified International Workshop on CLL National Cancer Institute – Working Group (IWCLL NCI-WG) Guidelines and:
• has an indication for treatment according to the 2008 Modified IWCLL NCI-WG Guidelines
• has clinically measurable disease (lymphocytosis > 5 × 10^9/L and/or palpable and measurable nodes by physical exam and/or organomegaly
assessed by physical exam)
• subjects with or without the 17p deletion or TP53 mutation are eligible
• subjects who have received prior B-cell receptor inhibitor therapy are also eligible (up to 60 subjects total will be enrolled in the study)
5. Adequate bone marrow function as follows:
• hemoglobin = 8.0 g/dL
• platelets = 25,000/mm^3 without any of the following:
o transfusion support within 14 days of Screening
o evidence of mucosal bleeding
o known history of major bleeding episode within 3 months of Screening

1. Soggetti di età = 18 anni.
2. Punteggio ECOG (Eastern Cooperative Oncology Group) = 2.
3. Soggetti con malattia recidivante/refrattaria (che hanno ricevuto almeno una terapia pregressa).
4. Diagnosi di CLL che soddisfa tutti i criteri previsti dalle Linee lineeguida (2008) del NCI-WG, aggiornate dall’IWCLL e che;
• pone indicazione per il trattamento in base ai criteri IWCLL NCI-WG 2008
• presenza di malattia clinicamente misurabile (linfocitosi > 5x 109/L e/o linfonodi palpabili e misurabili mediante esame obiettivo e/o organomegalia valutabile mediante esame obiettivo)
• con o senza delezione del cromosoma 17p o mutazione TP53.
• trattati in precedenza con un inibitore del recettore dei linfociti B (verranno arruolati fino a 60 soggetti in totale nella sperimentazione)
5. Adeguata funzione del midollo osseo confermata dai seguenti parametri:
• emoglobina =8.0 g/dL
• piastrine = 25.000/mm3 in assenza dei seguenti eventi:
o supporto trasfusionale nei 14 giorni precedenti lo Screening
o evidenza di sanguinamento dalle mucose
o storia nota di episodio di sanguinamento maggiore nei 3 mesi precedenti lo Screening

E.4

Principal exclusion criteria

1. Subject has developed Richter's transformation or Prolymphocytic leukemia (PLL)
2. Subject has previously received venetoclax.
3. History of active malignancies other than CLL within the past 2 years prior to first dose of venetoclax, with the exception of:
• adequately treated in situ carcinoma of the cervix uteri
• adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin
• previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
4. Active and uncontrolled autoimmune cytopenias (within 2 weeks prior to Screening), including autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP), despite low dose
corticosteroids.
5. Prior allogeneic stem cell transplant.

Soggetti che hanno sviluppato sindrome di Richter oppure leucemia prolinfocitica (prolymphocytic leukemia PLL)
2. Soggetti che hanno ricevuto venetoclax in precedenza.
3. Storia di neoplasia maligna attiva diversa dalla CLL nei 2 anni precedenti la prima dose di venetoclax, ad eccezione delle seguenti neoplasie:
• carcinoma in situ della cervice uterina trattato adeguatamente.
• carcinoma basocellulare o squamocellulare della pelle localizzato trattato adeguatamente
• neoplasia maligna pregressa circoscritta e trattata mediante resezione chirurgica (o trattata mediante altre modalità) con intento curativo.
4. Citopenie autoimmuni attive e non controllate (nelle 2 settimane precedenti lo Screening), compresa l’anemia emolitica autoimmune (autoimmune hemolytic anemia (AIHA) oppure la porpora trombocitopenica idiopatica (idiopathic thrombocytopenic purpura, ITP), nonostante il trattamento con corticosteroidi a basso dosaggio
5. Pregresso trapianto allogenico di cellule staminali.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint will be complete remission rate (CR + CRi) defined as the proportion of subjects achieving a (CR or Cri) of the subjects who have not been previously treated with BCRi therapy as assessed by the investigator.

L’endpoint primario di efficacia sarà misurato in base al tasso di remissione completa (CR + CRi) dei soggetti che non siano stati trattati in precedenza con inibitori dei Recettori dei Linfociti B, secondo la valutazione dello sperimentatore.

E.5.1.1

Timepoint(s) of evaluation of this end point

The date the last enrolled subject has completed their Week 48 disease assessment, or after all enrolled subjects have discontinued venetoclax, whichever is earlier, will be defined as the data "cutoff" date for the efficacy analyses

La data in cui l'ultimo soggetto arruolato abbia completato la valutazione della malattia alla settimana 48, o dopo che tutti i soggetti arruolati hanno interrotto venetoclax, se anteriore , sarà definita come data di " cut-off " per l'analisi di efficacia

E.5.2

Secondary end point(s)

Overall response rate, duration of response, time to progression, progression-free survival, overall survival, complete remission rate in BCell receptor inhibitor treated subjects

Tasso di Risposta Globale (ORR), Durata della Risposta (DOR), Tempo alla Progressione (TTP), Durata della Sopravvivenza Libera da Progressione (PFS), Sopravvivenza Globale (OS), Tasso di remissione completa nei soggetti trattati con inibitori dei recettori dei linfocitiB (BCell)

E.5.2.1

Timepoint(s) of evaluation of this end point

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

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)

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

E.8.1.1

Randomised

E.8.1.2

Open

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.8.2.4

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

Canada

Puerto Rico

Turkey

United States

Austria

Belgium

Denmark

Finland

France

Germany

Ireland

Italy

Netherlands

Norway

Portugal

Spain

Sweden

Switzerland

United Kingdom

Greece

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

Il termine della sperimentazione è definito come la data dell'ultima visita del'ultimo soggetto o la data dell'ultimo contatto di follow-up, quale avvenga dopo

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:

150

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

200

F.4.2.2

In the whole clinical trial

250

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)

In countries where venetoclax is not commercially available, subjects who continue to derive benefit after 2 years of treatment may be able to extend their treatment for up to 2 additional years: AbbVie will work with the investigator to consider the potential continuation of venetoclax therapy.

Nei paesi in cui venetoclax non è disponibile commercialmente, per i soggetti che continuano a ricevere beneficio dal trattamento dopo 2 anni di terapia, il trattamento potra essere esteso ad altri 2 anni: AbbVie lavorerà con lo sperimentatore per considerare la potenziale prosecuzione del trattamento con venetoclax.

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

2016-09-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-10-06

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-03-11

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