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Study of Lenalidomide Maintenance Versus Placebo in Responding Elderly Patients With DLBCL and Treated With R-CHOP (REMARC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01122472
Recruitment Status : Completed
First Posted : May 13, 2010
Last Update Posted : July 26, 2021
Sponsor:
Information provided by (Responsible Party):
The Lymphoma Academic Research Organisation

Tracking Information
First Submitted Date  ICMJE April 8, 2010
First Posted Date  ICMJE May 13, 2010
Last Update Posted Date July 26, 2021
Study Start Date  ICMJE April 2009
Actual Primary Completion Date June 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 21, 2015)
Progression-Free-Survival (PFS) [ Time Frame: Final PFS analysis will be realized when the number of events (160) has been reached or at the latest when the last patient into the study will finish follow up. The approximate schedule will be 75 months after the first patient randomized. ]
PFS will be measured from the date of randomization to the date of first documented disease progression or death. Progression data will be assigned to the earliest time when any progression is observed without prior missing assessments during the study up to the end of the follow up phase.
Original Primary Outcome Measures  ICMJE
 (submitted: May 12, 2010)
Progression-Free-Survival (PFS) [ Time Frame: Final PFS analysis will be realized when the number of events (282) has been reached or at the latest when the last patient into the study will finish follow up. The approximate schedule will be 75 months after the first patient randomized. ]
PFS will be measured from the date of randomization to the date of first documented disease progression or death.Progression data will be assigned to the earliest time when any progression is observed without prior missing assessments during the study up to the end of the follow up phase.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 21, 2015)
  • Overall survival (OS) [ Time Frame: 5 years ]
    From the date of randomization to the date of death from any cause Interim analysis of OS will be performed at the time of the PFS final analysis; it is projected to have 97 deaths at this time. Final analysis of OS at the end of the study, defined by the last visit of follow-up for the last patient randomized, 5 years after its randomization
  • Event-Free Survival (EFS) [ Time Frame: 5 years ]
    From the date of randomization to the date of first documented disease progression, relapse, initiation of new anti-lymphoma therapy or death from any cause Interim analysis of EFS will be performed at the time of the PFS final analysis. Final analysis of OS at the end of the study, defined by the last visit of follow-up for the last patient randomized, 5 years after its randomization
  • Response rate at the end of maintenance treatment [ Time Frame: 24 months ]
  • Percentage of patients who convert from PR (partial response) to CR (complete response) [ Time Frame: 24 months ]
  • Safety of lenalidomide in maintenance [ Time Frame: 5 years ]
    Toxicities occured during maintenance phase will be measured and reported from grade 2 for infection and neurological toxicities and from grade 3 for other toxicities according to CTCAE v3
  • PFS2 [ Time Frame: 5 years ]
    From randomization to objective tumor progression on next-line treatment or death from any cause
Original Secondary Outcome Measures  ICMJE
 (submitted: May 12, 2010)
  • Overall survival (OS) [ Time Frame: Approximate schedule to reach 278 deaths will be 78 months after the first patient has been randomized. ]
    OS will be set when 278 deaths have been observed or at least when the number of events for PFS (282) has been reached or at the latest when the last patient into the study will finish follow up. OS is from the date of randomization to the date of death from any cause
  • Event-Free Survival (EFS) [ Time Frame: Approximate schedule will be 78 months after the first patient has been randomized. ]
    EFS is from the date of randomization to the date of first documented disease progression or initiation of new anti-lymphoma therapy or death from any cause.
  • Response rate at the end of maintenance treatment [ Time Frame: From randomization to the end of the 24 months maintenance ]
  • Percentage of patients who convert from PR (partial response) to CR (complete response) [ Time Frame: From randomization to the end of maintenance treatment. Average of 74 months ]
  • Safety of lenalidomide in maintenance [ Time Frame: From randomization of the first patient to 3 years after the randomization of the last patient ]
    Toxicities occured during maintenance phase will be measured and reported from grade 2 for infection and neurological toxicities and from grade 3 for other toxicities according to CTCAE v3
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Lenalidomide Maintenance Versus Placebo in Responding Elderly Patients With DLBCL and Treated With R-CHOP
Official Title  ICMJE Double Blind Randomized Phase III Study of Lenalidomide Maintenance Versus Placebo in Responding Elderly Patients With DLBCL and Treated With R-CHOP in First Line
Brief Summary

This study is designed as a phase III, randomized, double-blind, placebo-controlled trial to explore the effect of maintenance therapy with lenalidomide versus placebo on progression-free survival (PFS) in patients treated with R-CHOP responding to induction therapy

For the primary efficacy variable, PFS, an improvement in median PFS from 38.6 months for Treatment Arm B to 54 months for Treatment Arm A (corresponding to a 2-year PFS of 65% vs 73.6%), is considered clinically relevant.

Detailed Description

Patients should have received at least 6 and up to 8 cycles of the R-CHOP 14 or R-CHOP 21 regimen or 6 R-CHOP-14 or -21 completed by 2 Rituximab alone in accordance to local preferences.

Patients can be registered to participate in the study at two time points:

  • At time of initial diagnosis and study enrolment (signature of informed consent) before the first cycle of treatment with R-CHOP.
  • At randomization (signature of informed consent) after treatment in first line with R-CHOP and have reached at least PR or CR.

Evaluation of the response to R-CHOP must be in accordance with Revised Response Criteria for Malignant Lymphoma(2007).

Stratification: Before randomization, the patients will be stratified according to the country and the response to R-CHOP (PR vs CR).

Randomization: Patients in CR/PR after R-CHOP will be randomized to maintenance therapy with lenalidomide or placebo.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Lymphoma
  • Diffuse Large B-cell Lymphoma
Intervention  ICMJE
  • Drug: Lenalidomide
    Daily for 3 weeks every 4 weeks for 24 months
    Other Name: Revlimid
  • Drug: Placebo
    Daily for 3 weeks every 4 weeks for 24 months
Study Arms  ICMJE
  • Experimental: Lenalidomide
    Lenalidomide daily for 3 weeks every 4 weeks for 24 months
    Intervention: Drug: Lenalidomide
  • Placebo Comparator: Placebo
    Placebo daily for 3 weeks every 4 weeks for 24 months
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 21, 2015)
650
Original Estimated Enrollment  ICMJE
 (submitted: May 12, 2010)
621
Actual Study Completion Date  ICMJE September 2019
Actual Primary Completion Date June 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Ages Eligible for Study: Between 60 and 80 years old

Genders Eligible for Study: Both

Accepts Healthy Volunteers: No

Inclusion Criteria:

For patients registered at the time of initial diagnosis

  • Patient with histologically proven CD20+ diffuse large B cel LYMPHOMA (DLBCL) 5WHO classification 2008) including clinical subtypes (primitive mediastinal, intravascular, etc.). Patients with De Novo Transformed DLBCL from low grade lymphoma (Follicular, other..) may also be included. Patients with DLBCL associated with some small cell infiltration in bone marrow may also be included Or CD20+ B-cell lymphoma with intermediate features between DLBCL and Burkitt or with intermediate features between DLBCL and classical Hodgkin lymphoma Or CD20+ Follicular lymphoma grade 3B Or CD20+ Aggressive B-cell lymphoma unclassifiable
  • previous untreated with chemo- or radiotherapy

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

  • Patient with histologically proven CD20+ diffuse large B cell LYMPHOMA (DLBCL) 5WHO classification 2008) including clinical subtypes (primitive mediastinal, intravascular, etc.). Patients with De Novo Transformed DLBCL from low grade lymphoma (Follicular, other..) may also be included. Patients with DLBCL associated with some small cell infiltration in bone marrow may also be included Or CD20+ B-cell lymphoma with intermediate features between DLBCL and Burkitt or with intermediate features between DLBCL and classical Hodgkin lymphoma Or CD20+ Follicular lymphoma grade 3B Or CD20+ Aggressive B-cell lymphoma unclassifiable
  • Have reached a CR or PR after first line treatment with at least 6 cycles of R-CHOP 14 regimens and up to 8 cycles of R-CHOP21
  • Previously untreated with Radiotherapy

For all patients:

  • aged from 60 to 80 years at time of registration
  • Ann Arbor stages II-IV at time of initial diagnosis
  • aaIPI> 1 at time of initial diagnosis
  • ECOG performance status 0-2
  • Minimum life expectancy of 3 months
  • Following laboratory values at screening:

    • ANC≥ 1000.10^6/L and Platelets≥60000.10^6/L
    • AST<5*ULN, ALT<5*ULN, Total Bilirubin<1,5*ULN
    • Creatinine clearance>30mL/min
  • Women are 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 not to father a child during participation in the trial and during the 12 months thereafter.
  • Having previously signed a written informed consent form

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 NYHA III-IV
  • Uncontrolled hypertension
  • Uncontrolled diabetes mellitus as defined by the investigator
  • Active systemic infection requiring treatment
  • previously known HIV positive serology
  • Active hepatitis B or C
  • Prior history of malignancies other than lymphoma within 3 years
  • Serious medical or psychiatric illness
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   France,   Israel,   Poland,   Portugal,   Spain,   Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01122472
Other Study ID Numbers  ICMJE REMARC
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party The Lymphoma Academic Research Organisation
Original Responsible Party Bertrand COIFFIER, GELARC
Current Study Sponsor  ICMJE The Lymphoma Academic Research Organisation
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account The Lymphoma Academic Research Organisation
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP