Clinical Trials Register

Summary
EudraCT Number:	2011-002565-38
Sponsor's Protocol Code Number:	CD-ON-MEDI-551-1088
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Temporarily Halted
Date on which this record was first entered in the EudraCT database:	2012-08-07
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

2011-002565-38

A.3

Full title of the trial

A Phase 2 Randomized Open-label Study of MEDI-551 in Adults
With Relapsed or Refractory DLBCL

Studio in aperto randomizzato di fase 2 su MEDI-551 in adulti con LDGCB recidivante o refrattario

A.3.1

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

A Phase 2 Randomized Open-label Study of MEDI-551 in Adults
With Relapsed or Refractory DLBCL

Studio in aperto randomizzato di fase 2 su MEDI-551 in adulti con LDGCB recidivante o refrattario

A.4.1

Sponsor's protocol code number

CD-ON-MEDI-551-1088

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01453205

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	MEDIMMUNE ONCOLOGY INC
B.1.3.4	Country	Netherlands
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	MedImmune LLC
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	MedImmune, LLC
B.5.2	Functional name of contact point	Information Center
B.5.3	Address:
B.5.3.1	Street Address	One MedImmune Way
B.5.3.2	Town/ city	Gaithersburg
B.5.3.3	Post code	20878
B.5.3.4	Country	United States
B.5.4	Telephone number	301 398-4012
B.5.5	Fax number	301 398-9012
B.5.6	E-mail	clinicaltrialenquiries@medimmune.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	MEDI-551
D.3.2	Product code	MEDI-551
D.3.4	Pharmaceutical form	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.3.9.2	Current sponsor code	MEDI-551
D.3.9.3	Other descriptive name	a-fucosylated anti-CD19 antibody
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	Yes
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	Yes
D.3.11.13.1	Other medicinal product type	Anticorpo Monoclonale
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	MEDI-551
D.3.2	Product code	MEDI-551
D.3.4	Pharmaceutical form	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.3.9.2	Current sponsor code	MEDI-551
D.3.9.3	Other descriptive name	a-fucosylated anti-CD19 antibody
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	Yes
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	Yes
D.3.11.13.1	Other medicinal product type	Anticorpo Monoclonale
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	MabThera
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration Ltd.
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 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	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	Yes
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	Yes
D.3.11.13.1	Other medicinal product type	Anticorpo monoclonale

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 or Refractory Diffuse Large B-cell Lymphoma .(DLBCL)

Linfoma diffuso a grandi cellule B recidivante o refrattario.(DLBCL)

E.1.1.1

Medical condition in easily understood language

Relapsed or Refractory Diffuse Large B-cell Lymphoma .(DLBCL)

Linfoma diffuso a grandi cellule B recidivante o refrattario.(DLBCL)

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	10012818
E.1.2	Term	Diffuse large B-cell lymphoma
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

E.2 Objective of the trial

E.2.1

Main objective of the trial

Determine if MEDI-551, when used in combination with salvage
chemotherapy, Ifosafamide-carboplatin-etoposide (ICE) or
Dexamethasone-cytarabine (DHAP) in patients with relapsed or
refractory DLBCL who are eligible for Autologous Stem Cell Tansplant
(ASCT), has superior efficacy compared to rituximab in the same
population.

Determinare se MEDI-551, se usato in combinazione con la chemioterapia di salvataggio, Ifosafamide-carboplatino-etoposide (ICE) o
Desametasone-citarabina (DHAP) in pazienti con DLBCL recidiva o
refrattaria che sono eligibili per trapianto autologo di cellule staminali (ASCT), ha efficacia superiore rispetto a rituximab nella stessa
popolazione.

E.2.2

Secondary objectives of the trial

Evaluate anti-tumor activities and overall survival (OS),to determine an
acceptable dose for MEDI-551 when used in combination with ICE or
DHAP, to describe the safety and tolerability, to determine the
immunogenicity (IM), and to describe the pharmacokinetic (PK) profile.

Valutare l'attività anti-tumorale e la sopravvivenza globale (OS),per determinare una
dose accettabile di Medi-551 quando usato in combinazione con ICE o
DHAP,per descriverne la sicurezza e tollerabilità,per determinarne l'
immunogenicità (IM),e per descriverne il profilo farmacocinetico (PK).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Histologically confirmed aggressive B-cell DLBCL, including FL
transforming to DLBCL & Grade III FL
• Relapsed from or refractory to at least one treatment containing
rituximab or another anti-CD20 based immunotherapy combined with
anthracycline- or anthracenedione-based chemotherapy
• Eligible for ASCT
• Eastern Cooperative Oncology Group (ECOG) performance status of 0,
1, or 2
• Life expectancy of ≥ 12 weeks
• Adequate hematological function

• DLBCL confermato istologicamente , comprese trasformazioni FL di DLBCL & FL di Grado III
• forma recidivante o refrattaria ad almeno un trattamento a base di
rituximab o un altro anti-CD20 immunoterapia basata sulla combinazione con antracicline o chemioterapia a base di antracendione
• eligibile per ASCT
• Eastern Cooperative Oncology Group (ECOG) performance status pari a 0,
1, o 2
• L'aspettativa di vita di ≥ 12 settimane
• Funzione ematologica adeguata

E.4

Principal exclusion criteria

• Any chemotherapy, radiotherapy, immunotherapy, biologic,
investigational or hormonal therapy for treatment of lymphoma within
28 days prior to treatment
• Previous cancer therapy for DLBCL other than anthracycline- or
anthracenedione based chemoimmunotherapy, monotherapy rituximab
prior to first line therapy and/or as a maintenance therapy, or limited
field radiotherapy
• Prior autologous or allogeneic SCT
• New York Heart Association ≥ Class II congestive heart failure;
• Clinically significant abnormality on ECG
• History of other invasive malignancy within 5 years except for
localized/in situ, carcinomas such as cervical carcinoma in situ.
• Evidence of active infection
• Documented current central nervous system involvement by leukemia
or lymphoma

• Qualsiasi chemioterapia, radioterapia, immunoterapia, biologica,
ormonale o terapia sperimentale per il trattamento del linfoma effettuato entro 28 giorni prima del trattamento
• terapia del cancro precedente per DLBCL diversa da antracicline o chemioimmunoterapia basata su
antracenedione , precedente monoterapia
di rituximab come terapia di prima linea e / o come terapia di mantenimento, o radioterapia a campo limitato.
• Precedente STC autologo o allogenico
• New York Heart Association ≥ insufficienza cardiaca congestizia di Classe II ;
• anormalità ECG clinicamente significativa
• Storia di altre neoplasie invasive entro 5 anni, salvo quelle
localizzata / in situ, carcinomi come il carcinoma cervicale in situ.
• Prove di infezione attiva
• Coinvolgimento attuale e documentato del sistema nervoso centrale da leucemia o linfoma

E.5 End points

E.5.1

Primary end point(s)

The overall response rate (ORR), including Partial Response (PR) and
Complete Response (CR), of subjects treated with MEDI-551 when used
in combination with ICE or DHAP versus rituximab in combination with
ICE or DHAP in subjects with relapsed or refractory DLBCL.

Il tasso di risposta globale (ORR), compresa la risposta parziale (PR) e
Risposta completa (CR), dei soggetti trattati con MEDI-551 quando viene utilizzato
in combinazione con ICE o DHAP rispetto a rituximab in combinazione con
ICE DHAP o in soggetti con DLBCL recidivato o refrattario.

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 1080

1080 giorni

E.5.2

Secondary end point(s)

Antitumor activity: Includes complete response rate, Minimal residual
disease negative complete response rate, time to response (TTR), time
to progression (TTP), progression-free survival (PFS), and overall
survival (OS)
Acceptable Dose: Benefit/Risk Analysis of Safety and Efficacy to be
determined
Safety and Tolerability: The safety endpoints include Adverse Events
(AEs), Serious Adverse Events (SAEs) occurring during the protocolspecified
reporting period and changes in clinical laboratory evaluations,
Electrocardiogram (ECGs), vital signs, and weight from baseline.
Immunogenicity (IM): Number and percentage of subjects who develop
detectable anti-drug antibodies
Pharmacokinetics (PK): Area Under Curve, CMAX, T1-half

Attività antitumorale: Include tasso di risposta completa, tasso negativo di risposta completa alla malattia minima residua, il tempo di risposta (TTR), il tempo alla progressione (TTP), sopravvivenza libera da progressione (PFS), e in generale
sopravvivenza (OS)
Dose Accettabile :Analisi per determinare il rapporto rischi / benefici della sicurezza e dell'efficacia.
Sicurezza e tollerabilità: Gli endpoint di sicurezza includono eventi avversi
(EA), eventi avversi gravi (SAE) che si verificano durante il periodo di riferimento specificato dal protocollo e i cambiamenti rispetto al basale nei risultati di laboratorio clinico, negli elettrocardiogrammi (ECG) e nei segni vitali e nel peso. Immunogenicità (IM): Numero e percentuale di soggetti che sviluppano anticorpi anti-farmaco rilevabili. Farmacocinetica (PK): area sotto la curva, CMAX, T1-mezzo

E.5.2.1

Timepoint(s) of evaluation of this end point

Antitumor activity: Study Day 1080
Acceptable dose: Study Day 42
Safety and Tolerability: Study Day 1080
IM: Up to Study Day 1080
PK: Study Day 1; Study Day 8; Study Day 12; Study Day 19; Study Day
26; Study Day 54; Study Day 110; Study Day 138; Study Day 166

Attività antitumorale: giorno 1080
Dose accettabile: giorno 42
Sicurezza e Tollerabilità: 1080
IM: fino al 1080
PK: giorni 1,8,12,19,26, 54, 110, 138, 166

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

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

Yes

E.8.2.3.1

Comparator description

rituximab - Stesso farmaco ad altro dosaggio

rituximab - same IMP used at different dosage

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

Canada

Israel

Japan

Russian Federation

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 study (''study completion'') is defined as the date of the last protocol-specified visit/assessment (including telephone contact) for the last subject in the study. This date will be after a combined total of 82 deaths occur in the rituximab arm and the selected MEDI-551 arm, or 24 months from the date the last subject is randomized into the study, or the date the sponsor stops the study, whichever occurs first.

La fine dello studio è definita come la data dell'ultima visita/valutazione specificata dal protocollo(compreso il contatto telefonico) per l'ultimo paziente.Questa data sarà dopo82decessi totali avvenuti in un braccio o 24 mesi dalla LPI.

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:

130

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

127

F.4.2.2

In the whole clinical trial

170

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)

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

2012-05-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-04-18

P. End of Trial
P.	End of Trial Status	Temporarily Halted

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Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
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