Clinical Trials Register

Summary
EudraCT Number:	2010-021253-39
Sponsor's Protocol Code Number:	SAKK 35/10
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2011-07-25
Trial 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

Denmark - DHMA

A.2

EudraCT number

2010-021253-39

A.3

Full title of the trial

Rituximab plus lenalidomide or rituximab monotherapy for untreated patients with follicular lymphoma in need of therapy. A randomized, open-label, multicentre phase II trial.

A.3.1

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

Rituximab plus lenalidomide or rituximab monotherapy for untreated patients with follicular lymphoma in need of therapy.

A.4.1

Sponsor's protocol code number

SAKK 35/10

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	Swiss Group for Clinical Cancer Research SAKK
B.1.3.4	Country	Switzerland
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	CELGENE International Sàrl
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	Swiss Group for Clinical Cancer Research
B.5.2	Functional name of contact point	Clinical Trial Management
B.5.3	Address:
B.5.3.1	Street Address	Effingerstrasse 40
B.5.3.2	Town/ city	Bern
B.5.3.3	Post code	3008
B.5.3.4	Country	Sweden
B.5.4	Telephone number	+4131389 91 91
B.5.5	Fax number	+4131389 92 00
B.5.6	E-mail	sakkcc@sakk.ch

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	Revlimid
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Europe 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	Yes
D.2.5.1	Orphan drug designation number	EU/3/03/177
D.3 Description of the IMP
D.3.1	Product name	Lenalidomide
D.3.4	Pharmaceutical form	Capsule, hard
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	LENALIDOMIDE
D.3.9.1	CAS number	191732-72-6
D.3.9.4	EV Substance Code	SUB25389
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	5
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	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	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	Yes
D.2.1.1.1	Trade name	Revlimid
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Europe 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	Yes
D.2.5.1	Orphan drug designation number	EU/3/03/177
D.3 Description of the IMP
D.3.1	Product name	Lenalidomide
D.3.4	Pharmaceutical form	Capsule, hard
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	LENALIDOMIDE
D.3.9.1	CAS number	191732-72-6
D.3.9.4	EV Substance Code	SUB25389
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	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	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	Yes
D.2.1.1.1	Trade name	Revlimid
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Europe 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	Yes
D.2.5.1	Orphan drug designation number	EU/3/03/177
D.3 Description of the IMP
D.3.1	Product name	Lenalidomide
D.3.4	Pharmaceutical form	Capsule, hard
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	LENALIDOMIDE
D.3.9.1	CAS number	191732-72-6
D.3.9.4	EV Substance Code	SUB25389
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	15
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	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	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

Untreated patients with follicular lymphoma in need of therapy.

E.1.1.1

Medical condition in easily understood language

Untreated patients with follicular lymphoma in need of therapy.

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	14.0
E.1.2	Level	PT
E.1.2	Classification code	10025310
E.1.2	Term	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

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To determine the activity of the combination of rituximab and lenalidomide given to untreated follicular lymphoma patients versus rituximab treatment.

E.2.2

Secondary objectives of the trial

Safety of the two therapy arms.

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

Translational research: Research on biological samples of follicular lymphoma patients searching for prognostic and predictive biomarkers for this disease:
-Translocation
-FcgR polymorphism & response
-Immunophenotyping
-Microenvironment
-Soluble micr RNA
-Immunomodulation & complement inhibition
-Endocannabinoid
-Signaling pathways
-Blood and tumor immune cells by flow cytometry
All material required for these projects will be obtained from the biobanks / sample banking.

E.3

Principal inclusion criteria

-Histologically confirmed FL CD20+; grade 1, 2, 3a; stage III+IV; stage II not suitable for radiotherapy
-Patients in need of systemic therapy: (at least one of these indications must be fulfilled)
•symptomatic enlarged lymph nodes, spleen or other lymphoma manifestations
•bulky disease ≥ 6 cm in long diameter
•clinically significant progression over at least 6 months of any tumor lesion
•anemia (Hb < 100 g/L) or thrombocytopenia (Platelets < 100 x 109/L) due to lymphoma
•clinically significant progressive decrease in Hb or platelet count due to lymphoma
•B-symptoms ,weight loss > 10 % in 6 months, drenching night sweats or fever > 38°C not due to infection
-Patients must have at least one two-dimensionally measurable lesion with longest transverse diameter > 10 mm
-Paraffin embedded tumor tissue is available for sending for pathology review
-Age > 18 years
-WHO performance status 0-2
-For patients with history of cardiac disease or older than 70 years: adequate cardiac function must be confirmed by EF ≥ 50%
-Adequate hematological values unless due to marrow infiltration by FL: (Neutrophils ≥ 1.5 x 109/l, Platelets ≥ 100 x 109/l)
-Adequate hepatic function: Bilirubin ≤ 1.5 x ULN (unless due to Gilbert’s syndrome), ALT/AP ≤ 2.5 x ULN
-Adequate renal function (calculated creatinine clearance ≥ 30 ml/min, according to the formula of Cockroft-Gault)
-Patient must give written informed consent before randomization
-Patient compliance and geographic proximity allow proper staging and follow-up
-Women with Childbearing potential
•are not pregnant and agree not to become pregnant during participation in the trial and during the 12 months thereafter
•are using effective contraception since 30 days at least
•have a negative pregnancy test within 4 days before randomization
-Men agree not to father a child, not to donate semen and to use condoms during trial treatment and 12 months thereafter
-Patients (male and female) agree to follow the special pregnancy prevention requirements for Revlimid® (lenalidomide)

E.4

Principal exclusion criteria

-Previous systemic therapy for follicular lymphoma
-Radiotherapy within the last 3 months
-Known CNS involvement
-Any serious underlying medical condition (at the judgment of the investigator) which could impair the ability of the patient to participate in the trial (e.g. active autoimmune disease, uncontrolled diabetes)
-Previous malignancy within 3 years with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer
-Psychiatric disorder precluding understanding information of trial related topics, giving informed consent, or interfering with compliance for oral drug intake
-Known hypersensitivity to trial drug(s) or hypersensitivity to any other component of the trial drugs
-Any concomitant drugs contraindicated for use with the trial drugs according to the approved product information
-Concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to trial entry
-Known HIV+ infection or HCV infection
-Patients with any serological evidence of current or past hepatitis B, unless the serological findings are clearly due to vaccination
-Patients regularly taking corticosteroids during the last 4 weeks, unless administered at a dose equivalent to Prednisone ≤ 15 mg/day for indications other than lymphoma or lymphoma-related symptoms
-Pregnant or lactating females

E.5 End points

E.5.1

Primary end point(s)

Complete response assessed at week 23 (+/- 1 week)

E.5.1.1

Timepoint(s) of evaluation of this end point

week 23 (1/- 1 week) after treatment start

E.5.2

Secondary end point(s)

Best Overall Response (OR) within 24 weeks
Best OR within 12 weeks
Best OR
Progression-free Survival
Duration of Complete Response
Time to first off-trial anti-lymphoma therapy
Overall Survival
AEs including lab abnormality assessments and vital signs

E.5.2.1

Timepoint(s) of evaluation of this end point

During follow-up phase of 10 years

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

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)

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 monotherapy

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

Switzerland

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

Last patient last visit refers in this trial to when the last patient had his second restaging and thus is evaluable for the primary endpoint, which is expected to be in Q4 2012.
All patients will be followed up for at least 10 years after randomization. Afterwards, in the following 10 years, information on survival, disease status and further treatment may be collected upon request of SAKK without scheduled trial visits. Overall collection of patient data lasts 20 years.

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:

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

100

F.4.2.2

In the whole clinical trial

152

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)

All patients will be followed up for at least 10 years after randomization. Afterwards, in the following 10 years, information on survival, disease status and further treatment may be collected upon request of SAKK without scheduled trial visits. Overall collection of patient data lasts 20 years.

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

2011-10-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-01-09

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2023-01-27

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