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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)

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ClinicalTrials.gov Identifier: NCT01650701
Recruitment Status : Active, not recruiting
First Posted : July 26, 2012
Last Update Posted : April 22, 2019
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
The Lymphoma Academic Research Organisation

Tracking Information
First Submitted Date  ICMJE July 24, 2012
First Posted Date  ICMJE July 26, 2012
Last Update Posted Date April 22, 2019
Study Start Date  ICMJE February 2012
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History Complete list of historical versions of study NCT01650701 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Follicular Lymphoma
Intervention  ICMJE
  • 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  ICMJE
  • 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, 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, López-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, André M, Zachée 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.

*   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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 18, 2019)
1030
Original Estimated Enrollment  ICMJE
 (submitted: July 24, 2012)
1000
Estimated Study Completion Date  ICMJE September 2024
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (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,   Belgium,   Canada,   France,   Germany,   Italy,   Portugal,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01650701
Other Study ID Numbers  ICMJE RV-FOL-GELARC-0683
2011-002792-42 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party The Lymphoma Academic Research Organisation
Study Sponsor  ICMJE The Lymphoma Academic Research Organisation
Collaborators  ICMJE Celgene Corporation
Investigators  ICMJE
Study Chair: Franck Morschhauser, MD, PhD The Lymphoma Study Association (LYSA)
PRS Account The Lymphoma Academic Research Organisation
Verification Date April 2019

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