Clinical Trials Register

Summary
EudraCT Number:	2010-023407-95
Sponsor's Protocol Code Number:	MO25455
National Competent Authority:	Lithuania - SMCA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-09-05
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

Lithuania - SMCA

A.2

EudraCT number

2010-023407-95

A.3

Full title of the trial

A randomized study comparing maintenance therapy with subcutaneous rituximab continued until progression with observation only in patients with relapsed or refractory, indolent non-Hodgkin’s lymphoma who completed and responded to rituximab-based
immunochemotherapy induction and initial 2-year rituximab maintenance therapy administered subcutaneously.

A.3.1

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

A Phase IIIb, randomized study comparing maintenance therapy with subcutaneous rituximab continued until progression and observation in patients with relapsed or refractory, indolent non-Hodgkin’s lymphoma who completed and responded to rituximab-based immunochemotherapy induction and initial 2-year rituximab maintenance therapy administered subcutaneously.

A.4.1

Sponsor's protocol code number

MO25455

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01461928

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	F. Hoffmann-La Roche Ltd
B.1.3.4	Country	Switzerland
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	F. Hoffmann-La Roche Ltd
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	F. Hoffmann-La Roche Ltd
B.5.2	Functional name of contact point	Trial Information Support Line-TISL
B.5.3	Address:
B.5.3.1	Street Address	Grenzacherstrasse 124
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4070
B.5.3.4	Country	Switzerland
B.5.6	E-mail	global.rochegenentechtrials@roche.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	Yes
D.2.1.1.1	Trade name	MabThera SC®
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration Limited
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.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous 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.3.9.2	Current sponsor code	Ro 045-2294
D.3.9.3	Other descriptive name	rituximab/rHuPH20 SC
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	120
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	recombinant humanized monoclonal antibody
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	Yes
D.2.1.1.1	Trade name	MabThera®
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration Limited
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.3.4	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.3.9.2	Current sponsor code	RO0452294
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	500
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	recombinant humanized monoclonal antibody

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 relapsed or refractory CD20+ follicular non-Hodgkin’s lymphoma (NHL) Grade 1, 2 or 3a, or other CD20+ indolent NHL (Waldenström’s macroglobulinemia or lymphoplasmacytic lymphoma, marginal zone lymphoma), according to the WHO classification system.

E.1.1.1

Medical condition in easily understood language

non-Hodgkin’s lymphoma (NHL)

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10067070
E.1.2	Term	Follicular B-cell non-Hodgkin's lymphoma
E.1.2	System Organ Class	100000004864

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 efficacy of a subcutaneous (SC) formulation of rituximab in term of progression-free survival after randomization (PFSrand) to either prolonged rituximab maintenance until progression (Maintenance II) or observation in patients with relapsed or refractory, indolent non-Hodgkin’s lymphoma who responded to Induction and initial 2 years maintenance therapy (Maintenance I).

E.2.2

Secondary objectives of the trial

To evaluate the efficacy and safety of SC rituximab during Induction, initial 2-year maintenance (Maintenance I) and randomized treatment period (Maintenance II). Efficacy will be evaluated in terms of Event-Free Survival (EFS), Time to Next Lymphoma Treatment (TNLT), Overall survival measured from the first Induction dose of rituximab (OSregist) and from the time of randomization to Maintenance II (OSrand), Overall Response Rate (ORR), Partial Response (PR) to Complete Response (CR) conversion rate at the end of Maintenance I, and PFS measured from the first Induction dose of rituximab (PFSregist). Safety assessments will include frequency of adverse events (AEs), serious adverse events (SAEs), and infusion/administration-related reactions (IRRs/ARRs) and immunoglobulin (Ig) quantification.

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

Select sites will also participate in the Time in Motion pharmacoeconomic sub-study that will assess Medical Care Utilization parameters. Details of the sub-study will be described in a separate protocol.
Protocol Title: Time and Motion Study of Rituximab (MabThera) Subcuteneous and Intraveneaous Formulations : M-10676.
Protocol Date and Version: February 27, 2012 Version 7.0.

E.3

Principal inclusion criteria

• Age ≥ 18 years.
• Histologically confirmed, CD20+ follicular NHL Grade 1, 2 or 3a, or other CD20+ indolent NHL (Waldenström’s macroglobulinemia or lymphoplasmacytic lymphoma, marginal zone lymphoma) according to the WHO classification system.
• Patients must have received, and must have relapsed or been refractory to, one or more lines of adequate therapy prior to enrolment, including at least one line consisting of immunotherapy and/or chemotherapy and/or radiotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

E.4

Principal exclusion criteria

• Transformation to high-grade lymphoma.
• Patients with aggressive lymphoma (e.g. mantle cell lymphoma).
• Presence or history of central nervous system (CNS) lymphomatous disease (e.g., CNS lymphoma or lymphomatous meningitis).
• Other malignancy within 5 years prior to enrolment, with the following exceptions (as long as curatively treated): carcinoma in situ of the cervix, squamous cell carcinoma of the skin, or basal cell skin cancer. Cervical carcinoma stage 1B or less, breast cancer in situ, or localized prostate cancer stage T1c or less may be considered, provided that the patient was treated with curative intent and has been relapse- and metastasis-free for at least 2 years prior to enrolment.
• Inadequate hepatic or renal function prior to the first rituximab induction dose.
• Known human immunodeficiency virus (HIV) infection.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint of the study is PFSrand. It is defined as the time from day of randomization to the first documented disease progression or death, whichever occurs first.

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 1 every 8 weeks [56 ± 7 days] until PD

E.5.2

Secondary end point(s)

Progression free survival (PFS) measured from the day of first rituximab Induction dose (PFSregist), Event-free survival (EFS), Time to next lymphoma treatment (TNLT), Overall survival measured from day of first rituximab Induction dose (OSregist) and from randomization (OSrand), Overall Response Rate (ORR) at the end of the Induction Phase and PR to CR conversion rate at the end of Maintenance I.

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 24 (cycle 8)

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

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

Yes

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

QUALITY OF LIFE (QOL)

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

observation arm (no treatment)

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

130

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

Albania

Argentina

Austria

Brazil

Bulgaria

Canada

Colombia

Ecuador

Egypt

France

Germany

Greece

Hungary

Italy

Lithuania

Norway

Romania

Russian Federation

Slovakia

Slovenia

Spain

Sweden

Switzerland

Turkey

United Kingdom

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 (EOS) is defined as the last patient’s last visit in Maintenance II. The study will end when all patients randomized in Maintenance II have been followed for at least 15 months after randomization, or earlier if the 129th PFS event has been reported or one of the following is documented for all patients: disease recurrence, withdrawal from the study, loss to follow-up or death.

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