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)

• ClinicalTrials.gov Identifier: NCT01650701
• Recruitment Status: Active, not recruiting
• First Posted: July 26, 2012
• Last Update Posted: March 15, 2024
• Sponsor: The Lymphoma Academic Research Organisation
• Collaborator: Celgene Corporation
• Information provided by (Responsible Party): The Lymphoma Academic Research Organisation

Tracking Information

• First Submitted Date: July 24, 2012
• First Posted Date: July 26, 2012
• Last Update Posted Date: March 15, 2024
• Actual Study Start Date: February 2012
• Actual Primary Completion Date: May 31, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 24, 2012)

• COMPLETE RESPONSE RATE [ Time Frame: Timeframe: CR/CRu rate at 120 weeks ]
  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) [ Time Frame: up to 13 years ]
  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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 24, 2012)

• Number of participants with adverse events [ Time Frame: up to13 years ]
• Time to Treatment Failure (TTF) [ Time Frame: up to13 years ]
• Event Free Survival (EFS) [ Time Frame: up to13 years ]
• Time to Next Anti-Lymphoma Treatment (TTNLT), [ Time Frame: up to13 years ]
• Time to Next Chemotherapy Treatment (TTNCT) [ Time Frame: up to13 years ]
• Overall Survival (OS) [ Time Frame: up to13 years ]
• Overall response rate at 120 weeks by International Working Group (IWG) 1999 criteria [ Time Frame: up to13 years ]
• Health related quality of life as measured by the EORTC QLQ-C30 [ Time Frame: up to13 years ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Follicular Lymphoma

Intervention

• Drug: Rituximab
  • 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.
  Other Names:

  • mabthera
  • rituxan
• Drug: Lenalidomide
  • 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
  Other Name: Revlimid
• Drug: Rituximab - CHOP
  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
• Drug: Rituximab - CVP
  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,
• Drug: Rituximab - Bendamustine
  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.

Study Arms

• Experimental: Lenalidomide + Rituximab
  • 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.
  Interventions:

  • Drug: Rituximab
  • Drug: Lenalidomide
• Active Comparator: Control
  • 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.
  Interventions:

  • Drug: Rituximab - CHOP
  • Drug: Rituximab - CVP
  • Drug: Rituximab - Bendamustine

Publications *

• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 18, 2019): 1030
• Original Estimated Enrollment (submitted: July 24, 2012): 1000
• Estimated Study Completion Date: April 2024
• Actual Primary Completion Date: May 31, 2017 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Canada, France, Germany, Italy, Portugal, Spain

Administrative Information

• NCT Number: NCT01650701
• Other Study ID Numbers: RV-FOL-GELARC-0683; 2011-002792-42 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: The Lymphoma Academic Research Organisation
• Original Responsible Party: Same as current
• Current Study Sponsor: The Lymphoma Academic Research Organisation
• Original Study Sponsor: Same as current
• Collaborators: Celgene Corporation

Investigators

• Study Chair: Franck Morschhauser, MD, PhD; The Lymphoma Study Association (LYSA)

• PRS Account: The Lymphoma Academic Research Organisation
• Verification Date: March 2024