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NCT01650701 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2025-09-25

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
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.
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. 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.
    intervention Names
    1. Drug: Rituximab
    2. Drug: Lenalidomide
    label
    Lenalidomide + Rituximab
    type
    EXPERIMENTAL
  2. 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 Names
    1. Drug: Rituximab - CHOP
    2. Drug: Rituximab - CVP
    3. Drug: Rituximab - Bendamustine
    label
    Control
    type
    ACTIVE_COMPARATOR
interventions
  1. arm Group Labels
    1. Lenalidomide + Rituximab
    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.
    name
    Rituximab
    other Names
    1. mabthera
    2. rituxan
    type
    DRUG
  2. arm Group Labels
    1. Lenalidomide + Rituximab
    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
    name
    Lenalidomide
    other Names
    1. Revlimid
    type
    DRUG
  3. arm Group Labels
    1. Control
    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
    name
    Rituximab - CHOP
    type
    DRUG
  4. arm Group Labels
    1. Control
    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,
    name
    Rituximab - CVP
    type
    DRUG
  5. arm Group Labels
    1. Control
    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.
    name
    Rituximab - Bendamustine
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
1030
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. 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.
    measure
    COMPLETE RESPONSE RATE
    time Frame
    Timeframe: CR/CRu rate at 120 weeks
  2. 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.
    measure
    Progression Free Survival (PFS)
    time Frame
    up to 13 years
secondary Outcomes
  1. measure
    Number of participants with adverse events
    time Frame
    up to13 years
  2. measure
    Time to Treatment Failure (TTF)
    time Frame
    up to13 years
  3. measure
    Event Free Survival (EFS)
    time Frame
    up to13 years
  4. measure
    Time to Next Anti-Lymphoma Treatment (TTNLT),
    time Frame
    up to13 years
  5. measure
    Time to Next Chemotherapy Treatment (TTNCT)
    time Frame
    up to13 years
  6. measure
    Overall Survival (OS)
    time Frame
    up to13 years
  7. measure
    Overall response rate at 120 weeks by International Working Group (IWG) 1999 criteria
    time Frame
    up to13 years
  8. measure
    Health related quality of life as measured by the EORTC QLQ-C30
    time Frame
    up to13 years
Full 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.
Source references
references
  1. citation
    Gower N, Feugier P, Westin J, Schiano De Colella JM, Tilly H, Palomba ML, Julia E, Damaj GL, Durand A, Flinn I, Lemonnier F, Morineau N, Ysebaert L, Bartlett N, Thieblemont C, Ribrag V, Gastinne T, Dony A, Fouillet L, Guidez S, Houot R, Da Silva MG, Barnes J, Bijou F, Cartron G, Garcia-Sancho AM, Eradat H, Cheminant M, Guillermo AL, Abrisqueta P, Abraham J, Sarkozy C, Izutsu K, Crochet G, Sehn LH, Gkasiamis A, Yge ML, Chartier L, Fowler N, Xerri L, Salles G, Morschhauser F. Lenalidomide plus rituximab for previously untreated advanced follicular lymphoma: the 10-year RELEVANCE trial analysis. Blood. 2026 Jun 18;147(25):3061-3068. doi: 10.1182/blood.2026033126.
    pmid
    41915772
    type
    DERIVED
  2. citation
    Claudel A, Cottereau AS, Bachy E, Itti E, Feugier P, Rossi C, Lemonnier F, Camus V, Daguindau N, Cartron G, Nicolas-Virelizier E, Mboumba DL, Cardoso C, Bommier C, Tessoulin B, Fruchart C, Gilbert A, Durot E, Fleck E, Pica GM, Zerazhi H, Guidez S, Cheminant M, Sarkozy C, Xerri L, Vercellino L, Trabelsi N, Gomes L, Portugues C, Viailly PJ, Delfau-Larue MH, Morschhauser F. Combined PET and ctDNA response as a predictor of POD24 for follicular lymphoma after first-line induction treatment. Blood. 2025 Aug 21;146(8):913-925. doi: 10.1182/blood.2024027727.
    pmid
    40499012
    type
    DERIVED
  3. citation
    Laurent C, Trisal P, Tesson B, Seth S, Beyou A, Roulland S, Lesne B, Van Acker N, Cerapio JP, Chartier L, Guille A, Stokes ME, Huang CC, Huet S, Gandhi AK, Morschhauser F, Xerri L. Follicular lymphoma comprises germinal center-like and memory-like molecular subtypes with prognostic significance. Blood. 2024 Dec 12;144(24):2503-2516. doi: 10.1182/blood.2024024496.
    pmid
    39374535
    type
    DERIVED
  4. 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.
    pmid
    35947804
    type
    DERIVED
  5. 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.
    pmid
    32673385
    type
    DERIVED
  6. 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.
    pmid
    30184451
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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      occurrences
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        Evidence (lenalidomide and rituximab):</p> <div class="pdq-content-list"><ol id="_1669"><li>In a randomized prospective trial (<a href="/clinicaltrials/NCT01650701">RELEVANCE</a> [NCT01650701]) of 1,030 patients with previously untreated follicular lymphoma, rituximab plus lenalidomide for 18 months was compared with ritu
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      2. context exact
        ituximab):</p> <div class="pdq-content-list"><ol id="_1669"><li>In a randomized prospective trial (<a href="/clinicaltrials/NCT01650701">RELEVANCE</a> [NCT01650701]) of 1,030 patients with previously untreated follicular lymphoma, rituximab plus lenalidomide for 18 months was compared with rituximab plus chemotherapy (usu
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      source title
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      source update dates
      1. context
        Updated: May 14, 2025
        datetime
        2025-05-14T12:00:00Z
        display
        May 14, 2025

    Preserved source evidence · Independent clinical review pending · Not medical advice