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A Phase 3 Open Label Randomized Study to Compare the Efficacy and Safety of Rituximab Plus Lenalidomide (CC-5013) Versus Rituximab Plus Chemotherapy Followed by Rituximab in Subjects With Previously Untreated Follicular Lymphoma (RELEVANCE)

Primary Purpose

Follicular Lymphoma

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Rituximab
Lenalidomide
Rituximab - CHOP
Rituximab - CVP
Rituximab - Bendamustine
Sponsored by
The Lymphoma Academic Research Organisation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Follicular Lymphoma focused on measuring follicular lymphoma, non-hodgkins follicular lymphoma, treatment for follicular lymphoma, rituximab treatment, rituximab and lenalidomide treatment

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically confirmed CD20+ follicular lymphoma grade 1, 2 or 3a
  • Have no prior systemic treatment for lymphoma.
  • Must be in need of treatment
  • Bi-dimensionally measurable disease with at least one mass lesion > 2 cm that was not previously irradiated.
  • Stage II, III or IV disease.
  • Must be ≥ 18 years and sign an informed consent.
  • Performance status ≤ 2 on the ECOG scale.
  • Adequate hematological function (unless abnormalities are related to lymphoma infiltration of the bone marrow)
  • Willing to follow pregnancy precautions

Exclusion Criteria:

  • Clinical evidence of transformed lymphoma by investigator assessment or Grade 3b follicular lymphoma.
  • Patients taking corticosteroids during the last 4 weeks, unless administered at a dose equivalent to < 10 mg/day prednisone (over these 4 weeks).
  • Major surgery (excluding lymph node biopsy) within 28 days prior to signing informed consent.
  • Known Seropositive for or active viral infection with hepatitis B virus (HBV), hepatitis C virus (HCV)or human immunodeficiency virus (HIV).
  • Life expectancy < 6 months.
  • Known sensitivity or allergy to murine products.
  • Prior history of malignancies, other than follicular lymphoma, unless the patient has been free of the disease for ≥ 10 years.
  • Prior use of lenalidomide.
  • Neuropathy > Grade 1.
  • Presence or history of CNS involvement by lymphoma.
  • Patients who are at a high risk for a thromboembolic event and are not willing to take venous thromboembolic (VTE) prophylaxis.
  • serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) > 3x upper limit of normal (ULN), except in patients with documented liver or pancreatic involvement by lymphoma
  • total bilirubin > 2.0 mg/dl (34 µmol/L) except in cases of Gilberts Syndrome and documented liver involvement by lymphoma
  • creatinine clearance of < 30 mL/min
  • Pregnant or lactating females.
  • Any condition, including the presence of laboratory abnormalities, which places the patient at unacceptable risk if he/she were to participate in the study, or which confounds the ability to interpret data from the study.

Sites / Locations

  • Concord Repatriation General Hospital
  • Nepean Hospital
  • Wollongong Hospital
  • CHU Mont-Godinne
  • Tom Baker Cancer Centre
  • Cross Cancer Institute
  • Fraser Valley Cancer Centre
  • BCCA - Vancouver Cancer Centre
  • Moncton Hospital
  • Atlantic Health Sciences Corp - Saint John Regional Hospital
  • Sunnybrook Health Sciences Centre
  • UHN-Princess Margaret Hospital
  • CHUM Hopital Notre-Dame
  • McGill University Department of Oncology
  • Hôpital de l'Enfant-Jesus, CHU de Quebec
  • Saskatoon Cancer Centre
  • CHU Claude Huriez
  • Medizinische Klinik der Universität Tübingen
  • Uniklinik Köln
  • LMU Munchën - Klinikum Grosshadern
  • Sant'Andrea Hospital
  • Policlinico Sant'Orsola-Malpighi
  • Instituto Português Oncologia
  • Hospital Virgen del Rocio
  • Hospital Universitario Mutua de Terrassa
  • Hospital Universitario de Canarias
  • Hospital Son Llatzer
  • Hospital Clínico de Barcelona
  • Hospital de la Santa Creu i Sant Pau
  • Hospital Universitario Vall d´Hebron
  • Institut Català d'Oncologia de Girona (ICO Girona)
  • Hospital Ramon y Cajal
  • Hospital Costa del Sol
  • Hospital Universitario Salamanca
  • Hospital Clínico Universitario de Valencia

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Lenalidomide + Rituximab

Control

Arm Description

Lenalidomide dose 20-mg on days 2-22 every 28 days x 6 cycles, if CR then 10-mg on days 2-22 every 28 days for 12 cycles. PR after 6 cycles, continue 20 mg for 3~6 cycles and then 10 mg on days 2-22 every 28-day cycles for upto 18 cycles Rituximab, 375 mg/m2 on days 1, 8, 15 and 22 of cycle 1, day 1 of cycles 2 to 6; 8 weeks later responding patients continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.

• ONE of the following: Rituximab - CHOP, Rituximab - CVP, Rituximab - Bendamustine. 7 to 8 weeks later responding patients will continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.

Outcomes

Primary Outcome Measures

COMPLETE RESPONSE RATE
Complete response (CR/CRu) rate at 120 weeks Response evaluation was as defined by International Working Group (IWG) Response Criteria (Cheson 1999). Complete response (CR) is defined as the complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms if present before therapy.
Progression Free Survival (PFS)
PFS is defined as the time from the start of study drug therapy to the 1st observation of disease progression or death due to any cause.

Secondary Outcome Measures

Number of participants with adverse events
Time to Treatment Failure (TTF)
Event Free Survival (EFS)
Time to Next Anti-Lymphoma Treatment (TTNLT),
Time to Next Chemotherapy Treatment (TTNCT)
Overall Survival (OS)
Overall response rate at 120 weeks by International Working Group (IWG) 1999 criteria
Health related quality of life as measured by the EORTC QLQ-C30

Full Information

First Posted
July 24, 2012
Last Updated
September 25, 2023
Sponsor
The Lymphoma Academic Research Organisation
Collaborators
Celgene Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT01650701
Brief Title
A Phase 3 Open Label Randomized Study to Compare the Efficacy and Safety of Rituximab Plus Lenalidomide (CC-5013) Versus Rituximab Plus Chemotherapy Followed by Rituximab in Subjects With Previously Untreated Follicular Lymphoma
Acronym
RELEVANCE
Official Title
A PHASE 3 OPEN-LABEL RANDOMIZED STUDY TO COMPARE THE EFFICACY AND SAFETY OF RITUXIMAB PLUS LENALIDOMIDE (CC-5013) VERSUS RITUXIMAB PLUS CHEMOTHERAPY FOLLOWED BY RITUXIMAB IN SUBJECTS WITH PREVIOUSLY UNTREATED FOLLICULAR LYMPHOMA The "RELEVANCE" Trial (Rituximab Lenalidomide Versus ANy ChEmotherapy)is Being Conducted as Two Companion Studies: RV-FOL-GELARC-0683 (N=750) and RV-FOL-GELARC-0683C (N=250); the Combined Total of 1000 Patients Enrolled in Both Studies Will be Analyzed.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 2012 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
September 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Lymphoma Academic Research Organisation
Collaborators
Celgene Corporation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to find out if lenalidomide when given along with rituximab can help to control the disease and also increase the length of your response (complete or partial response) compared to the standard of care rituximab chemotherapy treatment.
Detailed Description
Follicular Lymphoma (FL) is a cancer of a B lymphocyte, a type of white blood cell. FL is typically a slowly progressing but incurable disease. Follicular lymphoma cells produce a specific defect in the patient's immune system impairing their ability to control their cancer. Lenalidomide has been shown to reverse the specific immune defect caused by FL in the patient. By including lenalidomide, the RELEVANCE study aims to eliminate the cancer while restoring the patient's immune competence.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Follicular Lymphoma
Keywords
follicular lymphoma, non-hodgkins follicular lymphoma, treatment for follicular lymphoma, rituximab treatment, rituximab and lenalidomide treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1030 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lenalidomide + Rituximab
Arm Type
Experimental
Arm Description
Lenalidomide dose 20-mg on days 2-22 every 28 days x 6 cycles, if CR then 10-mg on days 2-22 every 28 days for 12 cycles. PR after 6 cycles, continue 20 mg for 3~6 cycles and then 10 mg on days 2-22 every 28-day cycles for upto 18 cycles Rituximab, 375 mg/m2 on days 1, 8, 15 and 22 of cycle 1, day 1 of cycles 2 to 6; 8 weeks later responding patients continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.
Arm Title
Control
Arm Type
Active Comparator
Arm Description
• ONE of the following: Rituximab - CHOP, Rituximab - CVP, Rituximab - Bendamustine. 7 to 8 weeks later responding patients will continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
mabthera, rituxan
Intervention Description
• Rituximab, 375 mg/m2 on days 1, 8, 15 and 22 of cycle 1, day 1 of cycles 2 to 6; 8 weeks later responding patients continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
Revlimid
Intervention Description
• Lenalidomide dose 20-mg on days 2-22 every 28 days x 6 cycles, if CR then 10-mg on days 2-22 every 28 days for 12 cycles. PR after 6 cycles, continue 20 mg for 3~6 cycles and then 10 mg on days 2-22 every 28-day cycles for upto 18 cycles
Intervention Type
Drug
Intervention Name(s)
Rituximab - CHOP
Intervention Description
six cycles of R-CHOP in 21 day cycles followed by two 21 day cycles of 375 mg/m2 rituximab; and 7 weeks later responding patients continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles
Intervention Type
Drug
Intervention Name(s)
Rituximab - CVP
Intervention Description
eight cycles of R-CVP in 21 day cycles; and 7 weeks later responding patients continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles,
Intervention Type
Drug
Intervention Name(s)
Rituximab - Bendamustine
Intervention Description
six cycles of R-B in 28 day cycles and 8 weeks later responding patients continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.
Primary Outcome Measure Information:
Title
COMPLETE RESPONSE RATE
Description
Complete response (CR/CRu) rate at 120 weeks Response evaluation was as defined by International Working Group (IWG) Response Criteria (Cheson 1999). Complete response (CR) is defined as the complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms if present before therapy.
Time Frame
Timeframe: CR/CRu rate at 120 weeks
Title
Progression Free Survival (PFS)
Description
PFS is defined as the time from the start of study drug therapy to the 1st observation of disease progression or death due to any cause.
Time Frame
up to 13 years
Secondary Outcome Measure Information:
Title
Number of participants with adverse events
Time Frame
up to13 years
Title
Time to Treatment Failure (TTF)
Time Frame
up to13 years
Title
Event Free Survival (EFS)
Time Frame
up to13 years
Title
Time to Next Anti-Lymphoma Treatment (TTNLT),
Time Frame
up to13 years
Title
Time to Next Chemotherapy Treatment (TTNCT)
Time Frame
up to13 years
Title
Overall Survival (OS)
Time Frame
up to13 years
Title
Overall response rate at 120 weeks by International Working Group (IWG) 1999 criteria
Time Frame
up to13 years
Title
Health related quality of life as measured by the EORTC QLQ-C30
Time Frame
up to13 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed CD20+ follicular lymphoma grade 1, 2 or 3a Have no prior systemic treatment for lymphoma. Must be in need of treatment Bi-dimensionally measurable disease with at least one mass lesion > 2 cm that was not previously irradiated. Stage II, III or IV disease. Must be ≥ 18 years and sign an informed consent. Performance status ≤ 2 on the ECOG scale. Adequate hematological function (unless abnormalities are related to lymphoma infiltration of the bone marrow) Willing to follow pregnancy precautions Exclusion Criteria: Clinical evidence of transformed lymphoma by investigator assessment or Grade 3b follicular lymphoma. Patients taking corticosteroids during the last 4 weeks, unless administered at a dose equivalent to < 10 mg/day prednisone (over these 4 weeks). Major surgery (excluding lymph node biopsy) within 28 days prior to signing informed consent. Known Seropositive for or active viral infection with hepatitis B virus (HBV), hepatitis C virus (HCV)or human immunodeficiency virus (HIV). Life expectancy < 6 months. Known sensitivity or allergy to murine products. Prior history of malignancies, other than follicular lymphoma, unless the patient has been free of the disease for ≥ 10 years. Prior use of lenalidomide. Neuropathy > Grade 1. Presence or history of CNS involvement by lymphoma. Patients who are at a high risk for a thromboembolic event and are not willing to take venous thromboembolic (VTE) prophylaxis. serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) > 3x upper limit of normal (ULN), except in patients with documented liver or pancreatic involvement by lymphoma total bilirubin > 2.0 mg/dl (34 µmol/L) except in cases of Gilberts Syndrome and documented liver involvement by lymphoma creatinine clearance of < 30 mL/min Pregnant or lactating females. Any condition, including the presence of laboratory abnormalities, which places the patient at unacceptable risk if he/she were to participate in the study, or which confounds the ability to interpret data from the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Franck Morschhauser, MD, PhD
Organizational Affiliation
The Lymphoma Study Association (LYSA)
Official's Role
Study Chair
Facility Information:
Facility Name
Concord Repatriation General Hospital
City
Concord
State/Province
New South Wales
Country
Australia
Facility Name
Nepean Hospital
City
Penrith
State/Province
New South Wales
Country
Australia
Facility Name
Wollongong Hospital
City
Wollongong
State/Province
New South Wales
Country
Australia
Facility Name
CHU Mont-Godinne
City
Yvoir
Country
Belgium
Facility Name
Tom Baker Cancer Centre
City
Calgary
State/Province
Alberta
Country
Canada
Facility Name
Cross Cancer Institute
City
Edmonton
State/Province
Alberta
Country
Canada
Facility Name
Fraser Valley Cancer Centre
City
Surrey
State/Province
British Columbia
Country
Canada
Facility Name
BCCA - Vancouver Cancer Centre
City
Vancouver
State/Province
British Columbia
Country
Canada
Facility Name
Moncton Hospital
City
Moncton
State/Province
New Brunswick
Country
Canada
Facility Name
Atlantic Health Sciences Corp - Saint John Regional Hospital
City
Halifax
State/Province
Nova Scotia
Country
Canada
Facility Name
Sunnybrook Health Sciences Centre
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
UHN-Princess Margaret Hospital
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
CHUM Hopital Notre-Dame
City
Montreal
State/Province
Quebec
Country
Canada
Facility Name
McGill University Department of Oncology
City
Montreal
State/Province
Quebec
Country
Canada
Facility Name
Hôpital de l'Enfant-Jesus, CHU de Quebec
City
Quebec city
State/Province
Quebec
Country
Canada
Facility Name
Saskatoon Cancer Centre
City
Saskatoon
State/Province
Saskatchewan
Country
Canada
Facility Name
CHU Claude Huriez
City
Lille
Country
France
Facility Name
Medizinische Klinik der Universität Tübingen
City
Tübingen
State/Province
Baden Wurtemberg
Country
Germany
Facility Name
Uniklinik Köln
City
Köln
State/Province
Nordrhein
Country
Germany
Facility Name
LMU Munchën - Klinikum Grosshadern
City
Munchen
Country
Germany
Facility Name
Sant'Andrea Hospital
City
Roma
State/Province
Lazio
Country
Italy
Facility Name
Policlinico Sant'Orsola-Malpighi
City
Bologna
Country
Italy
Facility Name
Instituto Português Oncologia
City
Lisboa
Country
Portugal
Facility Name
Hospital Virgen del Rocio
City
Sevilla
State/Province
Andaloucia
Country
Spain
Facility Name
Hospital Universitario Mutua de Terrassa
City
Terrassa
State/Province
Barcelona
Country
Spain
Facility Name
Hospital Universitario de Canarias
City
Santa Cruz de Tenerife
State/Province
Canarias
Country
Spain
Facility Name
Hospital Son Llatzer
City
Palma
State/Province
Mallorca
Country
Spain
Facility Name
Hospital Clínico de Barcelona
City
Barcelona
Country
Spain
Facility Name
Hospital de la Santa Creu i Sant Pau
City
Barcelona
Country
Spain
Facility Name
Hospital Universitario Vall d´Hebron
City
Barcelona
Country
Spain
Facility Name
Institut Català d'Oncologia de Girona (ICO Girona)
City
Girona
Country
Spain
Facility Name
Hospital Ramon y Cajal
City
Madrid
Country
Spain
Facility Name
Hospital Costa del Sol
City
Marbella
Country
Spain
Facility Name
Hospital Universitario Salamanca
City
Salamanca
Country
Spain
Facility Name
Hospital Clínico Universitario de Valencia
City
Valencia
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35947804
Citation
Morschhauser F, Nastoupil L, Feugier P, Schiano de Colella JM, Tilly H, Palomba ML, Bachy E, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Le Gouill S, Daguindau N, Guidez S, Pica GM, Garcia-Sancho AM, Lopez-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, Andre M, Kalung W, Sehn LH, Izutsu K, Cartron G, Gkasiamis A, Crowe R, Xerri L, Fowler NH, Salles G. Six-Year Results From RELEVANCE: Lenalidomide Plus Rituximab (R2) Versus Rituximab-Chemotherapy Followed by Rituximab Maintenance in Untreated Advanced Follicular Lymphoma. J Clin Oncol. 2022 Oct 1;40(28):3239-3245. doi: 10.1200/JCO.22.00843. Epub 2022 Aug 10.
Results Reference
derived
PubMed Identifier
32673385
Citation
Delfau-Larue MH, Boulland ML, Beldi-Ferchiou A, Feugier P, Maisonneuve H, Casasnovas RO, Lemonnier F, Pica GM, Houot R, Ysebaert L, Tilly H, Eisenmann JC, Le Gouill S, Ribrag V, Godmer P, Glaisner S, Cartron G, Xerri L, Salles GA, Fest T, Morschhauser F. Lenalidomide/rituximab induces high molecular response in untreated follicular lymphoma: LYSA ancillary RELEVANCE study. Blood Adv. 2020 Aug 11;4(14):3217-3223. doi: 10.1182/bloodadvances.2020001955.
Results Reference
derived
PubMed Identifier
30184451
Citation
Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, Lopez-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, Andre M, Zachee P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. doi: 10.1056/NEJMoa1805104.
Results Reference
derived

Learn more about this trial

A Phase 3 Open Label Randomized Study to Compare the Efficacy and Safety of Rituximab Plus Lenalidomide (CC-5013) Versus Rituximab Plus Chemotherapy Followed by Rituximab in Subjects With Previously Untreated Follicular Lymphoma

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