Clinical Trials Register

Summary
EudraCT Number:	2007-001666-32
Sponsor's Protocol Code Number:	APM4083g
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:	2010-03-02
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

2007-001666-32

A.3

Full title of the trial

A PHASE II, RANDOMIZED, DOUBLE-BLIND,PLACEBO-CONTROLLED STUDY OF THE SAFETY,PHARMACOKINETICS, AND EFFICACY OF MULTIPLE DOSES OF APOMAB ADMINISTERED INTRAVENOUSLY IN COMBINATION WITH RITUXIMAB IN PATIENTS WITH FOLLICULAR, CD20-POSITIVE B-CELL NON-HODGKIN’S LYMPHOMA THAT HAS PROGRESSED FOLLOWING PREVIOUS RITUXIMAB THERAPY
ESTUDIO FASE II, ALEATORIZADO , DOBLE CIEGO, CONTROLADO CON PLACEBO PARA VALORAR LA SEGURIDAD, FARMACOCINÉTICA Y EFICACIA DE MULTIPLES DOSIS DE APOMAB ADMINISTRADAS POR VIA INTRAVENOSA EN COMBINACIÓN CON RITUXIMAB EN PACIENTES CON LINFOMA NON HODGKING FOLICULAR CON CELULAS B CD20 POSITIVAS QUE HAN PROGRESADO DESPUÉS DE UNA TERAPIA PREVIA CON RITUXIMAB

A.4.1

Sponsor's protocol code number

APM4083g

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Genentech Inc
B.1.3.4	Country	United States
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	Apomab
D.3.4	Pharmaceutical form	Intravenous infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	PRO95780
D.3.9.3	Other descriptive name	Apomab
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	15
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)	Information not present in EudraCT
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	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	Information not present in EudraCT
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	Information not present in EudraCT
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	Monoclonal Antibody
D.IMP: 2
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	F.Hoffman La-Roche
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	Mabthera
D.3.4	Pharmaceutical form	Intravenous infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	Rituximab
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	375
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)	Information not present in EudraCT
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	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	Information not present in EudraCT
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	Information not present in EudraCT
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	Monoclonal Antibody

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Intravenous infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Follicular, CD20-Positive B-Cell Non-Hodgkin's Lymphoma
Linfoma Non-Hodgking folicular con céluas B CD20 positivas

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10029593
E.1.2	Term	Non-Hodgkin's lymphoma NOS

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the safety and tolerability of Apomab when combined with rituximab for the treatment of patients with relapsed follicular, CD20-positive B-cell non-Hodgkin’s
lymphoma (NHL). To make a preliminary assessment of the efficacy of Apomab when combined with rituximab for the treatment of patients with relapsed follicular, CD20-positive B-cell NHL, as measured byobjective response rate.

E.2.2

Secondary objectives of the trial

To make a preliminary assessment of the efficacy of Apomab when combined with rituximab for the treatment of patients with relapsed follicular, CD20-positive B-cell NHL, as measured by progression-free survival, duration of response, and overall survival. To evaluate the serum pharmacokinetics of Apomab and rituximab when combined for the treatment of patients with relapsed follicular, CD20-positive B-cell NHL.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

>Signed Informed Consent Form
> Age ≥18 years
>Diagnosis of follicular, CD20-positive B-cell NHL classified as Grade 1, 2, or
3a according to the WHO classification of malignant lymphomas
>Progression of disease after an objective response (CR/CRu or PR) or SD
lasting 6 months following completion of the most recent rituximab-containing regimen
>A rituximab-containing regimen is defined as rituximab as a single agent
during induction and/or maintenance, or in combination with other agents.
>Measurable disease (according to modified IWG Criteria; see Appendix B)
ECOG performance status of 0 or 1 (see Appendix D)
>Life expectancy of 3 months
>Willingness and capability to be accessible for follow-up until study
termination or death
>For patients of reproductive potential (both males and females), use of a
reliable means of contraception (e.g., contraceptive pill, intrauterine device
[IUD], barrier methods) throughout the trial and for 1 year following their last
exposure to study treatment

E.4

Principal exclusion criteria

>Grade 3b follicular lymphoma (according to the WHO classification) or
histologic transformation from follicular lymphoma to aggressive lymphoma
>Prior radiotherapy to a lesion(s) that will be used to assess response unless
that lesion(s) shows clear evidence of lymphoma progression at baseline
(i.e., ≥50% increase in the product of the longest perpendicular diameters of
the lesion [greatest transverse diameter perpendicular diameter] when
compared with the nadir of lesion dimensions following radiotherapy and
1.5 cm in the greatest transverse diameter)
>Radiotherapy to a peripheral lesion within 14 days prior to Cycle 1, Day 1 or
radiotherapy to a thoracic, abdominal, or pelvic field within 28 days prior to
Cycle 1, Day 1
>Prior radio-immunotherapy, including radiolabeled antibodies
>Concurrent systemic corticosteroid therapy (except low-dose corticosteroid
therapy used to treat an illness other than lymphoma)
>Other invasive malignancies within 5 years prior to Cycle 1, Day 1 (other than
basal or squamous cell carcinoma of the skin or in situ carcinoma of the
cervix treated with curative intent)
>History or evidence on physical examination of central nervous system
(CNS) disease (e.g., primary brain tumor, CNS lymphoma, seizures not
controlled with standard medical therapy, any brain metastases, or history
of stroke)
>Prior treatment with agonistic DR4 or DR5 antibodies or Apo2L/TRAIL
>General Medical Concerns
>Current or recent (within the 28 days prior to Cycle 1, Day 1) participation in
another experimental drug study
>Clinically significant cardiovascular disease (e.g., uncontrolled hypertension,
myocardial infarction within 1 year prior to Cycle 1, Day 1, unstable angina),
New York Heart Association (NYHA; see Appendix E) Grade II or greater
congestive heart failure, serious cardiac arrhythmia requiring medication
within 1 year prior to Cycle1, Day 1, or Grade II or greater peripheral vascular
disease (see Appendix F) at study entry
>Active infection requiring parenteral antibiotics on Cycle 1, Day 1
Protocol: Apomab—Genentech,
>Major surgical procedure (excluding lymph node biopsy) or significant
traumatic injury within 28 days prior to Cycle 1, Day 1, or anticipation of need
for major surgical procedure during the course of the study
>Pregnancy (positive pregnancy test) or breast feeding
>Serious, non-healing wound, ulcer, or bone fracture
Laboratory values
ANC 1500/L (may not be treated with G-CSF to maintain or exceed
this level) Platelet count 75,000/L Total bilirubin1.6 mg/dL AST or ALT 2.5 the upper limit of normal (ULN) Serum creatinine 2.0 mg/dL or measured creatinine clearance
≤50 mL/min Hemoglobin 9 g/dL (may not be transfused or treated with erythropoietin to maintain or exceed this level)
>Known human immunodeficiency virus (HIV) infection, seropositivity for
hepatitis B surface antigen (HBsAg), hepatitis B IgG or IgM core antibody,
or hepatitis C virus (HCV) antibody
>History of other disease, metabolic dysfunction, physical finding,
or laboratory finding giving reasonable suspicion of a disease or condition
that contraindicates use of an investigational drug or that might affect
interpretation of the results of the study or render the patient at high risk from
treatment complications

E.5 End points

E.5.1

Primary end point(s)

Objective response (defined as a PR or CR/CRu, occurring within 8 months post-randomization), as determined by the IRF using modified IWG Criteria

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

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

Information not present in EudraCT

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

Information not present in EudraCT

E.7.1.2

Bioequivalence study

Information not present in EudraCT

E.7.1.3

Other

Information not present in EudraCT

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

Information not present in EudraCT

E.7.4

Therapeutic use (Phase IV)

Information not present in EudraCT

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

Information not present in EudraCT

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

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

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	No
F.1.1.1	In Utero	Information not present in EudraCT
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	Information not present in EudraCT
F.1.1.3	Newborns (0-27 days)	Information not present in EudraCT
F.1.1.4	Infants and toddlers (28 days-23 months)	Information not present in EudraCT
F.1.1.5	Children (2-11years)	Information not present in EudraCT
F.1.1.6	Adolescents (12-17 years)	Information not present in EudraCT
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Information not present in EudraCT
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	12
F.4.2	For a multinational trial
F.4.2.1	In the EEA	25
F.4.2.2	In the whole clinical trial	80

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

2008-03-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-01-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2009-12-31

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