Clinical Trials Register

Summary
EudraCT Number:	2012-002620-32
Sponsor's Protocol Code Number:	CCR3862
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2013-02-11
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2012-002620-32

A.3

Full title of the trial

A randomised phase II study comparing LEnalidomide plus rituximab, GEmcitabine and methylprednisolone (LR-GEM) to rituximab, gemcitabine, methylprednisolone and cisplatiN (R-GEM-P) in second-line treatment of Diffuse Large B-cell lymphoma (DLBCL)

A.3.1

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

A randomised study to test the effectiveness of LEnalidomide plus rituximab, GEmcitabine and methylprednisolone (LR-GEM) in comparison to rituximab, gemcitabine, methylprednisolone and cisplatiN (R-GEM-P) in treatment of Diffuse Large B-cell lymphoma (DLBCL) for the second time (when it has relapsed or grown despite the first treatment)

A.3.2

Name or abbreviated title of the trial where available

LEGEND

A.4.1

Sponsor's protocol code number

CCR3862

A.5.4

Other Identifiers

Name:

Celgene protocol number

Number:

RV-DLBCL-PI-0765

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	The Royal Marsden NHS Foundation Trust
B.1.3.4	Country	United Kingdom
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
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Royal Marsden NHS Foundation Trust
B.5.2	Functional name of contact point	Ms Bijal Patel
B.5.3	Address:
B.5.3.1	Street Address	Downs Road,
B.5.3.2	Town/ city	Sutton, Surrey
B.5.3.3	Post code	SM2 5PT
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	020 8661 3808
B.5.5	Fax number	020 86613750
B.5.6	E-mail	bijal.patel@rmh.nhs.uk

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 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	Information not present in EudraCT
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Lendalidomide
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.3.9.2	Current sponsor code	CC-5013
D.3.9.3	Other descriptive name	CDC-501
D.3.9.4	EV Substance Code	AS1
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	25
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.3.9.2	Current sponsor code	CC-5013
D.3.9.3	Other descriptive name	CDC-501
D.3.9.4	EV Substance Code	AS2
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	20
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.3.9.2	Current sponsor code	CC-5013
D.3.9.3	Other descriptive name	CDC-501
D.3.9.4	EV Substance Code	AS3
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.3.8 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.3.9.2	Current sponsor code	CC-5013
D.3.9.3	Other descriptive name	CDC-501
D.3.9.4	EV Substance Code	AS4
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.3.8 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.3.9.2	Current sponsor code	CC-5013
D.3.9.3	Other descriptive name	CDC-501
D.3.9.4	EV Substance Code	AS5
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.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes

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.

E.1.1.1

Medical condition in easily understood language

cancer of the lymphatic system of the body, originating in B-cells (type of white blood cells), when is has already been treated with chemotherapy once, but has grown back again.

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	10012821
E.1.2	Term	Diffuse large B-cell lymphoma recurrent
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

To assess the complete response rate (rate of patients put into remission) of treatment with LR-GEM (lenalidomide, rituximab, gemcitabine and methylprednisolone) and R-GEM-P (rituximab, gemcitabine, cisplatin and methylprednisolone) following 3 cycles of induction treatment as second-line therapy for patients with diffuse large B-cell lymphoma (DLBCL)(a common type of aggressive lymphoma in adults).

E.2.2

Secondary objectives of the trial

To assess, in both arms:
• Overall response rate following 3 cycles of induction treatment
• Event-free survival
• Overall survival
• Rate of successful stem cell harvest
• Toxicity
• Subgroup analyses will be performed to assess whether variation in the following factors causes a difference in the primary endpoint result: cell-of-origin immunohistochemical subtype using the Choi classification method(GCB vs non-GCB), morphological subtype (centroblastic vs immunoblastic vs other), International Prognostic Index (IPI)((0-2 vs 3 or more), time to relapse from previous treatment (< or equal to 12 vs > 12 months), and eligibility for ASCT at randomisation

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Histologically proven CD20+ Diffuse Large B-Cell Lymphoma (DLBCL)
2. Availability of a tumour block containing adequate histological material for central pathology review and establishment of morphological and ontogenic subtype. Surgically acquired tissue samples are preferred but if core biopsy is the only suitable means by which to acquire a tissue sample then it is suggested than at least 2 cores are taken so that one can be embedded and sent for central review and one retained locally.
3. Relapsed after or refractory to one prior line of chemotherapy for DLBCL containing both rituximab and an anthracycline (eg R-CHOP)
o ‘Relapsed’ is defined as investigator assessed progression after first line treatment
o ‘Refractory’ is defined as patients who progressed during or who did not achieve complete remission with first line treatment (which should include radiotherapy if the patient had localised refractory disease)
4. Eligible for combination chemotherapy regimen
5. Patient is ≥18 years of age on the day of signing informed consent.
6. ECOG performance status 0, 1 or 2.
7. Baseline PET/CT scans must demonstrate FDG avid disease compatible with CT defined anatomical tumour sites.
8. Adequate bone marrow function: absolute neutrophil count (ANC) ≥1.0x109/l; white blood cell count ≥ 3x109/l; platelets ≥ 100x109/l; haemoglobin (Hb) ≥ 9g/dl (can be post-transfusion), unless deemed disease related
9. Adequate renal function: calculated creatinine clearance ≥40ml/minute.
10. Adequate liver function: serum bilirubin ≤1.5x ULN; ALT/AST ≤2.5x ULN; ALP ≤3x ULN (in the absence of liver metastases). If liver metastases are present, ALT, AST or ALP ≤5x ULN are permitted. Isolated hyperbilirubinaemia due to Gilbert’s disease is acceptable
11. Female patient of childbearing potential (FCBP) must have two negative serum β-hCG pregnancy tests at baseline.
12. FCBP agreeable to practice sexual abstinence or use two forms of contraception from 28 days prior to the period of study treatment and for 12 months after the last dose of study drugs.
13. Male patients agreeable to practice sexual abstinence use condoms from 28 days prior to the period of study treatment and for 12 months after the last dose of study drugs.
14. Recovery from toxicity from previous anti-cancer treatment to ≤ grade 1

E.4

Principal exclusion criteria

1. Documented or symptomatic central nervous system involvement or leptomeningeal disease.
2. Any other clinically significant disease or co-morbidity which may adversely affect the safe delivery of treatment within this trial, including active or chronic infection, poorly controlled diabetes mellitus, congestive cardiac failure, cardiac arrhythmia, coronary artery disease, cerebrovascular disease, or severe pulmonary disease
3. Any other malignancies diagnosed or treated within the last 5 years (other than curatively treated basal cell or squamous cell carcinoma of the skin and/or in situ carcinoma of the cervix or breast).
4. Received drug treatment for cancer within 21 days of commencing study treatment.
5. Received previous lenalidomide
6. Evidence of human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or active hepatitis B infection.
7. Patient is pregnant or breastfeeding, or expecting to conceive or father children within one year of finishing study treatment.
8. Hypersensitivity or contraindication to any of the study drugs as stated in the SmPCs for each of the study drugs.
9. Prior stem cell or solid organ transplant
10. Treatment with an investigational product within 30 days prior to enrolment
11. Not able to provide fully informed consent because of intellectual impairment or psychiatric disorder
12. Patient unwilling or not able to adhere to the Lenalidomide Pregnancy Prevention Programme (Appendix I)

E.5 End points

E.5.1

Primary end point(s)

To assess the complete response rate after 3 cycles of induction treatment to R-GEM-P and LR-GEM. Complete response rate is assessed using the Modified IWG Revised Response Criteria for Malignant Lymphoma 2007, based on central review by the trial radiologists, and incorporating bone marrow aspirate and trephine results. Assessment will be done in a blinded fashion.

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary outcome measure will be evaluated after 3 cycles of induction treatment.

E.5.2

Secondary end point(s)

To compare, between both arms:
• Overall response rate following 3 cycles of induction treatment evaluated by IWG 2007 criteria (Cheson JCO 2007)
• Event-free survival
• Overall survival
• Rate of successful stem cell harvest
• Toxicity
• Subgroup analyses will be performed on the primary endpoint by cell-of-origin immunohistochemical subtype using the Choi method(GCB vs non-GCB), morphological subtype (centroblastic vs immunoblastic vs other), IPI (0-1 vs 2), and previous response to treatment (12 vs > 12 months), and eligibility for ASCT at randomisation

E.5.2.1

Timepoint(s) of evaluation of this end point

Overall response rate will be evaluated after 3 cycles of induction treatment. rate of successful stem cell harvest will be evaluated after 3 cycles of induction treatment plus 2 weeks. Subgroup analyses and toxicity can be evaluated after 3 cycles of induction treatment. Overall survival, event-free survival and toxicity will be evaluated once all patients have a minimum of 2 years on study, and again at the end of the study.

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

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

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

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

LVLS

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