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Trial registered on ANZCTR


Registration number
ACTRN12611000085976
Ethics application status
Approved
Date submitted
23/12/2010
Date registered
24/01/2011
Date last updated
20/08/2019
Date data sharing statement initially provided
20/08/2019
Date results information initially provided
20/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Study of Lenalidomide Maintenance Versus Placebo in Responding Elderly Patients With Diffuse Large B cell Lymphoma (DLBCL) and Treated With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP)
Scientific title
Double blind randomized phase III study of
Lenalidomide (Revlimid Registered Trademark) maintenance versus
Placebo in responding elderly patients with
diffuse large B cell lymphoma (DLBCL) and treated with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in first line
Secondary ID [1] 253330 0
Clinical trials.gov NCT01122472
Universal Trial Number (UTN)
Trial acronym
REMARC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diffuse large B cell lymphoma (DLBCL) in elderly patients 258870 0
Condition category
Condition code
Cancer 259007 259007 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
25mg daily lenalidomide for 21 days of a 28 day cycle of maintenance therapy for up to 26 cycles. Lenalidomide is an oral tablet.
Intervention code [1] 257783 0
Treatment: Drugs
Comparator / control treatment
placebo oral tablet contains the excipients used for the drug product without the active ingredient and it conforms to the colour and size for blinded study. It is taken daily for 21 days of a 28 day cycle of maintenance therapy for up to 26 cycles.
Control group
Placebo

Outcomes
Primary outcome [1] 259864 0
to determine the benefit estimated by the progression-free survival associated with lenalidomide maintenance compared to placebo in responding patients treated with R-CHOP for diffuse large B-cell lymphoma. Progression will be measured by tests such as CT scan, PET scan and Bone Marrow examination.
Timepoint [1] 259864 0
The primary endpoint will be analysed when a total of 160 progression or death events have occurred, or at the latest, when 5 years median follow-up has been met.
Secondary outcome [1] 268738 0
Overall survival (OS) in both groups of patients (with and without lenalidomide maintenance)
Timepoint [1] 268738 0
OS is from the date of randomization to the date of death from any cause. An interim analysis of OS will be performed at the time of PFS analysis. At study closure, the final analysis of OS will be conducted.
Secondary outcome [2] 268739 0
The number and percentage of patients who convert from partial response (PR) at the end of induction treatment
to complete response (CR) at the end of maintenance treatment
Timepoint [2] 268739 0
From randomisation until end of maintenance therapy
Secondary outcome [3] 268740 0
efficacy according to the response to R-CHOP and will be measured by tests such as CT scan, PET scan and Bone Marrow examination.
Timepoint [3] 268740 0
From randomization to the end of the 24 months maintenance
Secondary outcome [4] 268741 0
safety of lenaliodmide in maintenance and will be measured by medical reviews and blood tests
Timepoint [4] 268741 0
60 days after last dose of study treatment
Secondary outcome [5] 268742 0
Response rate at the end of maintenance treatment will be measured by tests such as CT scan, PET scan, Cheson 2007 criteria, blood tests, tumor biopsy and Bone Marrow examination.
Timepoint [5] 268742 0
From randomization to the end of 24 months maintenance
Secondary outcome [6] 335283 0
Second relapse/progression (PFS2) as measured by time from randomisation to objective tumour progression on next-line treatment or death from any cause, Time to event analysis will be conducted. The recurrent event approach will also be used to take account of the first and second progression.
Timepoint [6] 335283 0
An interim analysis of second relapse/progression (PFS2) will be performed at the time of PFS analysis. At study closure, the final analysis of PFS2 will be conducted.

Eligibility
Key inclusion criteria
For patients registered at the time of initial diagnosis

initial diagnosis of histologically confirmed CD20+ DLBCL
previously untreated with chemo- or radiotherapy

For patients registered after response evaluation to first line treatment with R-CHOP:

Diagnosis of histologically confirmed CD20+ diffuse large B-Cell Lymphoma
Have reached a CR or PR after first line treatment with at least 6 cycles of R-CHOP 14 regimen or up to 8 cycles of R-CHOP21
Previously untreated with Radiotherapy

For all patients:

aged from 60 to 80 years at time of initial diagnosis
Ann Arbor stages II-IV at time of initial diagnosis
age-adjusted International Prognostic Index greater than 1 at time of initial diagnosis
Eastern Cooperative Oncology Group performance status 0-2
Minimum life expectancy of 3 months
Following laboratory values at screening:

absoloute neutrophil count greater than or equal to 1000x10^6/Litre and Platelets greater than or equal to 60000x10^6/Litre
Aspartate transaminase (AST) less than or equal to 5x Upper limit of normal (ULN), Alanine transaminase (ALT) less than or equal to 5xULN, Total Bilirubin less than or equal to 1.5xULN
Creatinine clearance>30mL/min
Women of childbearing potential are using effective contraception, are not pregnant and agree not to become pregnant during participation in the trial and after end of study. Men agree to use a condom during sexual contact with a female, even if they have had a vasectomy, and to not donate semen or sperm throughout study drug therapy, during any dose interruption and during the 12 months thereafter.
Having previously signed a written informed consent form
Minimum age
60 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Any other histological type of lymphoma, Burkitt included.
Any history of treated or non-treated small B-cell lymphoma
Central nervous system or meningeal involvement by lymphoma
Contraindication to any drug contained in the chemotherapy regimen.
Myocardial infarction during last 3 months or unstable coronary disease or uncontrolled chronic
symptomatic congestive heart insufficiency New York Heart Association III-IV
Uncontrolled hypertension
Uncontrolled diabetes mellitus as defined by the investigator
Active systemic infection requiring treatment.
Previously known human immunodeficiency virus (HIV) positive serology
Active hepatitis B or C
Prior history of malignancies other than lymphoma within 3 years (except for complete resection of basal cell carcinoma, squamous cell carcinoma of the skin, or in situ malignancy)
Serious medical or psychiatric illness likely to interfere with participation in this clinical study

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients can be either registered before induction therapy or after induction therapy. Randomization should occur after documentation of CR or PR and maintenance treatment will start within 8 weeks after the first day of the last R-CHOP cycle. Randomisation will occur through a central registration centre.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
random number allocated by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,ACT,QLD,SA,WA,TAS
Recruitment postcode(s) [1] 3517 0
3002
Recruitment postcode(s) [2] 3518 0
2137
Recruitment postcode(s) [3] 3519 0
3690
Recruitment postcode(s) [4] 3520 0
3084
Recruitment postcode(s) [5] 3521 0
5000
Recruitment postcode(s) [6] 3522 0
4215
Recruitment postcode(s) [7] 3523 0
7001
Recruitment postcode(s) [8] 3524 0
6000
Recruitment postcode(s) [9] 3525 0
6009
Recruitment postcode(s) [10] 3526 0
2217
Recruitment postcode(s) [11] 3527 0
3065
Recruitment outside Australia
Country [1] 3106 0
Belgium
State/province [1] 3106 0
Country [2] 3107 0
France
State/province [2] 3107 0
Country [3] 3108 0
Portugal
State/province [3] 3108 0

Funding & Sponsors
Funding source category [1] 258252 0
Other Collaborative groups
Name [1] 258252 0
GELA
Address [1] 258252 0
Centre Hospitalier Lyon Sud - Secteur Sainte Eugenie
(Batiment 6D) - Chemin du Grand Revoyet
69310 Pierre Benite
Country [1] 258252 0
France
Funding source category [2] 258253 0
Other Collaborative groups
Name [2] 258253 0
Australasian Leukaemia and Lymphoma Group
Address [2] 258253 0
Level 6, 372 Albert St
East Melbourne, Victoria, 3002
Country [2] 258253 0
Australia
Funding source category [3] 258254 0
Commercial sector/Industry
Name [3] 258254 0
Celgene Global
Address [3] 258254 0
Celgene Corporation
86 Morris Avenue
Summit, NJ 07901
1-908-673-9000
Country [3] 258254 0
United States of America
Primary sponsor type
Other Collaborative groups
Name
Australasian Leukaemia and Lymphoma Group
Address
Level 6, 372 Albert St
East Melbourne, Victoria, 3002
Country
Australia
Secondary sponsor category [1] 257419 0
Other Collaborative groups
Name [1] 257419 0
GELA
Address [1] 257419 0
Centre Hospitalier Lyon Sud - Secteur Sainte Eugenie
(Batiment 6D) - Chemin du Grand Revoyet
69310 Pierre Benite
Country [1] 257419 0
France

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 260229 0
Sydney local Health District Human Research Ethics Committee (CRGH)
Ethics committee address [1] 260229 0
Concord Repatriation General Hospital
Building 20, Hospital Road, Concord NSW 2139
Ethics committee country [1] 260229 0
Australia
Date submitted for ethics approval [1] 260229 0
01/02/2011
Approval date [1] 260229 0
07/02/2011
Ethics approval number [1] 260229 0
Ethics committee name [2] 304138 0
Austin Health Human Research Ethics Committee
Ethics committee address [2] 304138 0
Office for Research,
L8 Harold Stokes Building, Austin Health
145 Studley Road, Heidelberg, VIC 3084 AUSTRALIA
Ethics committee country [2] 304138 0
Australia
Date submitted for ethics approval [2] 304138 0
Approval date [2] 304138 0
Ethics approval number [2] 304138 0
Ethics committee name [3] 304139 0
Sir Charles Gairdner Hospital
Ethics committee address [3] 304139 0
Ground floor, A Block
Hospital Avenue, Nedlands,
Western Australia 6009
Ethics committee country [3] 304139 0
Australia
Date submitted for ethics approval [3] 304139 0
Approval date [3] 304139 0
Ethics approval number [3] 304139 0
Ethics committee name [4] 304140 0
Human Research Ethics Committee (Tasmania) Network
Ethics committee address [4] 304140 0
Office of Research Services
University of Tasmania
Private Bag 1
Hobart Tasmania 7001
Ethics committee country [4] 304140 0
Australia
Date submitted for ethics approval [4] 304140 0
Approval date [4] 304140 0
Ethics approval number [4] 304140 0

Summary
Brief summary
In patients between 60-80 years with diffuse large B cell lymphoma (DLBCL), the current standard treatment is R-CHOP chemotherapy (consisting of the drugs Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone). However the probability of being alive and free of lymphoma 5 years after diagnosis is only 54%. Lenalidomide is an immune system modulating drug that has anti-lymphoma properties demonstrated in smaller studies of patients with relapsed/refractory DLBCL. Given the high risk of relapsed DLBCL in this older patient population this study is aimed at determining whether Lenalidomide maintenance taken orally for 21 days every 4 weeks can safely reduce the risk of progression/relapse of DLBCL. Who is it for? This study is open to patients aged between 60 and 80 years and currently underoing R-CHOP combination therapy for diffuse large B-cell lymphoma. Trial details Participants will be randomised into one of two arms, (1) 25mg daily lenalidomide for 21 days of a 28 day cycle of maintenenace therapy for up to 26 cycles, or (2) a placebo instead of the active drug over the same period. The aim of the study is to reduce the risk of progression/relapse of DLBCL
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32041 0
Prof Judith Trotman
Address 32041 0
Concord Repatriation General Hospital Hospital Road Concord, NSW, 2139
Country 32041 0
Australia
Phone 32041 0
+61 2 9767 7243
Fax 32041 0
Email 32041 0
judith.trotman@health.nsw.gov.au
Contact person for public queries
Name 15288 0
Ms Narmatha Kuru
Address 15288 0
Biostatistics and Clinical Trials
Peter Mac Cancer Centre
Level 2/10 St Andrews place
East Melbourne, VIC, 3002
Country 15288 0
Australia
Phone 15288 0
+61 3 9656 5807
Fax 15288 0
Email 15288 0
narmatha.kuru@petermac.org
Contact person for scientific queries
Name 6216 0
Prof Judith Trotman
Address 6216 0
Concord Repatriation General Hospital
Hospital Road
Concord, NSW, 2139
Country 6216 0
Australia
Phone 6216 0
+61 2 9767 7243
Fax 6216 0
Email 6216 0
judith.trotman@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No individual participant data will be publicly available as it is the aggregate data that is under investigation.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary