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

• ClinicalTrials.gov Identifier: NCT01122472
• Recruitment Status: Completed
• First Posted: May 13, 2010
• Last Update Posted: July 26, 2021
• Sponsor: The Lymphoma Academic Research Organisation
• Information provided by (Responsible Party): The Lymphoma Academic Research Organisation

Tracking Information

• First Submitted Date: April 8, 2010
• First Posted Date: May 13, 2010
• Last Update Posted Date: July 26, 2021
• Study Start Date: April 2009
• Actual Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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.

Current Secondary Outcome Measures (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 (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: Study of Lenalidomide Maintenance Versus Placebo in Responding Elderly Patients With DLBCL and Treated With R-CHOP
• Official Title: 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: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Lymphoma
• Diffuse Large B-cell Lymphoma

Intervention

• 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

• 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 *

• Cottereau AS, Meignan M, Nioche C, Capobianco N, Clerc J, Chartier L, Vercellino L, Casasnovas O, Thieblemont C, Buvat I. Risk stratification in diffuse large B-cell lymphoma using lesion dissemination and metabolic tumor burden calculated from baseline PET/CTdagger. Ann Oncol. 2021 Mar;32(3):404-411. doi: 10.1016/j.annonc.2020.11.019. Epub 2020 Dec 3.
• Vercellino L, Cottereau AS, Casasnovas O, Tilly H, Feugier P, Chartier L, Fruchart C, Roulin L, Oberic L, Pica GM, Ribrag V, Abraham J, Simon M, Gonzalez H, Bouabdallah R, Fitoussi O, Sebban C, Lopez-Guillermo A, Sanhes L, Morschhauser F, Trotman J, Corront B, Choufi B, Snauwaert S, Godmer P, Briere J, Salles G, Gaulard P, Meignan M, Thieblemont C. High total metabolic tumor volume at baseline predicts survival independent of response to therapy. Blood. 2020 Apr 16;135(16):1396-1405. doi: 10.1182/blood.2019003526.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 21, 2015): 650
• Original Estimated Enrollment (submitted: May 12, 2010): 621
• Actual Study Completion Date: September 2019
• Actual Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 60 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, France, Israel, Poland, Portugal, Spain, Switzerland

Administrative Information

• NCT Number: NCT01122472
• Other Study ID Numbers: REMARC
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: The Lymphoma Academic Research Organisation
• Original Responsible Party: Bertrand COIFFIER, GELARC
• Current Study Sponsor: The Lymphoma Academic Research Organisation
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: The Lymphoma Academic Research Organisation
• Verification Date: July 2021