Clinical Trials Register

Summary
EudraCT Number:	2011-005851-15
Sponsor's Protocol Code Number:	GAINED
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2012-10-24
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2011-005851-15

A.3

Full title of the trial

A RANDOMIZED PHASE III STUDY USING A PET-DRIVEN STRATEGY AND COMPARING GA101 OR RITUXIMAB IN COMBINATION WITH A CHEMOTHERAPY DELIVERED EVERY 14 DAYS (ACVBP OR CHOP) IN DLBCL CD20+ LYMPHOMA UNTREATED PATIENTS FROM 18 TO 60 PRESENTING WITH 1 OR MORE ADVERSE PROGNOSTIC FACTORS OF THE AGE-ADJUSTED IPI

A.3.1

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

Study for patients with diffuse large B cell lymphoma from 18 to 60 years, evaluating a new antibody, GA101 and a PET driven strategy.

A.3.2

Name or abbreviated title of the trial where available

GA IN NEWLY DIAGNOSED DLBCL

A.4.1

Sponsor's protocol code number

GAINED

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01659099

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	LYSARC
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	F. Hoffmann-La Roche Ltd
B.4.2	Country	Switzerland
B.4.1	Name of organisation providing support	LYSARC
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Alexia SCHARTZMANN - LYSARC
B.5.2	Functional name of contact point	Project Manager
B.5.3	Address:
B.5.3.1	Street Address	Centre Hospitalier Lyon Sud - Secteur Sainte Eugénie - Pavillon 6D
B.5.3.2	Town/ city	Pierre-Bénite Cedex
B.5.3.3	Post code	69495
B.5.3.4	Country	France
B.5.4	Telephone number	+33(0)472669333
B.5.5	Fax number	+33(0)472669371
B.5.6	E-mail	alexia.schartzmann@lysarc.org

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	Obinutuzumab
D.3.2	Product code	GA101
D.3.4	Pharmaceutical form	Solution for injection/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	GA101
D.3.9.1	CAS number	949142-50-1
D.3.9.3	Other descriptive name	OBINUTUZUMAB
D.3.9.4	EV Substance Code	SUB32751
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	25
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)	Yes
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	No
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	Roche Registration 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	rituximab
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.3.8	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/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)	Yes
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 histologically proven CD20+ diffuse large B cell lymphoma (WHO Classification), Aged ≥18 years and ≤60 years, with Age adjusted International Prognostic Index (aa-IPI) equal to 1, 2 or 3

E.1.1.1

Medical condition in easily understood language

Patients from 18 to 60 years, with diffuse large B cell lymphoma CD20+, with 1, 2 or 3 adverse prognostic factors of the aa-IPI.

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	18.0
E.1.2	Level	HLGT
E.1.2	Classification code	10025320
E.1.2	Term	Lymphomas non-Hodgkin's B-cell
E.1.2	System Organ Class	10005329 - Blood and lymphatic system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to demonstrate an improvement of the 2-year Event Free Survival (EFS) in DLBCL CD20+ patients aged from 18 to 60 years with 1 to 3 adverse prognostic factors of the aa-IPI treated with GA101 or Rituximab in combination with ACVBP14 or CHOP14 in a PET-driven strategy.

E.2.2

Secondary objectives of the trial

- Early metabolic response rate according to PET after 2 and 4 cycles
- Overall Response rate and Best Overall Response after 4 cycles and at end of treatment according to Cheson 2007 (CR, CRu and PR) criteria
- Overall Response rate and Best Overall Response after 4 cycles and at end of treatment according to Cheson 1999 (CR, CRu and PR) criteria.
- Safety of the two antibodies (Rituximab vs GA101) and of the two chemotherapy regimen in the whole population and in the two arms of treatment (R-ACVBP14 vs GA101-ACVBP14 and R-CHOP14 vs GA101-CHOP14).
- Duration of response, progression-free survival and overall survival in the whole population, in the two inductive arms (R-Chemo14 vs GA101-Chemo14)

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

- Analysis on blood samples and on tumor tissue biopsy to determine biological factors of the patients and their tumors that influence treatment response based on PET assessment and prognosis.
- Focus on subpopulation: Duration of response, PFS and OS will be performed according to treatment arms (R-Chemo14 vs GA101-Chemo14) on different analysis populations: Population with a ΔSUVmaxPET0-2≤66%, population with a ΔSUVmaxPET0-2>66%, patents submitted to autologous stem cell transplant (PFS and OS only)
- Stem cell harvest evaluation after GA101 treatment

E.3

Principal inclusion criteria

• Histologically proven CD20+ diffuse large B cell lymphoma (WHO Classification)
• Baseline PET scan available with at least one hypermetabolic lesion
• Aged ≥18 years and ≤60 years
• Eligible for autologous stem cell transplant
• Patient not previously treated
• Age adjusted International Prognostic Index (aa-IPI) equal to 1, 2 or 3
• Life expectancy ≥ 3 months
• Negative HIV, HBV (anti-HBc negativity) and HCV serologies before inclusion
• Having signed a written informed consent
• Having ability and willingness to comply with study protocol procedures
• Men must agree to use a barrier method of contraception during the treatment period and until 3 months after the last dose of GA101 or rituximab, or ACVBP14 or CHOP14 chemotherapy, whichever is longer
• Women of childbearing potential must agree to use an adequate method of contraception, such as oral contraceptives, intrauterine device, or barrier method of contraception during the treatment period and until 12 months after the last dose of GA101, Rituximab, ACVBP14, or CHOP14 chemotherapy, whichever is longer

E.4

Principal exclusion criteria

• Any other histological type of lymphoma
• Any history of treated or non-treated indolent lymphoma. However, patients not previously diagnosed and having a diffuse large B-cell lymphoma with some small cell infiltration in bone marrow or lymph node may be included
• Central nervous system or meningeal involvement by lymphoma
• Contra-indication to any drug contained in the chemotherapy regimens
• Poor cardiac function (LVEF <50%) on echocardiogram or MUGA scan
• Poor renal function (creatinine level>150*mol/l or clearance <30ml/min), poor hepatic function (total bilirubin level>30µmol/l, transaminases>2.5 X maximum normal level) unless these abnormalities are related to the lymphoma
• Poor bone marrow reserve as defined by neutrophils < 1.5 G/L or platelets < 100 G/L, unless related to bone marrow infiltration
• Any history of cancer during the last 5 years, with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma
• Any serious active disease (according to the investigator’s decision)
• Prior history of Progressive Multifocal Leukoencephalopathy (PML)
• Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy
• Pregnant or lactating women
• Adult patient under tutelage

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is the Event Free Survival (EFS)

E.5.1.1

Timepoint(s) of evaluation of this end point

EFS will be defined as the period from the date of randomization until the date of first occurrence of an event. An event is defined as:
- PET positivity according to ΔSUVmax criteria after 2 or 4 induction cycles, as defined by RAC (based on central PET review),
- Progression or relapse, according to Cheson 2007
- Modification of planned treatment non-related to progression, including radiotherapy.
- Death of any cause.

E.5.2

Secondary end point(s)

• Early metabolic response according to PET after 2 and 4 cycles
• Overall Response rate and Best overall response after 4 cycles and end of treatment according to Cheson 2007 criteria
• Overall Response Rate and Best overall response after 4 cycles and end of treatment according to Cheson 1999 criteria
• Duration of response (DoR)
• Progression-Free Survival (PFS)
• Overall survival (OS)

E.5.2.1

Timepoint(s) of evaluation of this end point

Response will be assessed after 4 cycles and again at the end of treatment, based on RAC assessment for PET 4 and investigator assessment for EoT PET.
Response will be assessed after 4 cycles and at the end of treatment, based on investigator assessment.
Duration of response is defined as the period from the time of attainment a CR or PR to the date of progression, relapse or death from any cause.
Progression-Free Survival is defined as the period from the date of randomization to the date of first documented disease progression, relapse, or death from any cause.
Overall survival is defined as the period from the date of randomization to the date of death from any cause.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

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

Yes

E.6.13.1

Other scope of the trial description

- To evaluate the interest of a PET driven strategy by these patients

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

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

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

120

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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 is defined as the last patient’s last visit and will occur approximately 6.5 years (78 months) after the first patient is enrolled to allow all patients to have a minimum of 3 years of follow-up post treatment.

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:

670

F.1.3

Elderly (>=65 years)

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Information not present in EudraCT

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

120

F.4.2

For a multinational trial

F.4.2.1

In the EEA

670

F.4.2.2

In the whole clinical trial

670

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)

Patients who receive the complete treatment won't be treated after this study, except in case of relapse.
Patients who withdraw the study will receive a salvage therapy.

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

2013-01-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-05-13

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

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