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Follicular LymphomaPhase 3RELEVANCENCT01476787

Combined Rituximab and Lenalidomide Treatment for Untreated Patients With Follicular Lymphoma

A Phase 3 study testing Rituximab, Lenalidomide and Rituximab-CHOP in people with Follicular Lymphoma, run by Celgene at 36 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to evaluate the effect of the combined treatment of lenalidomide and rituximab in controlling the Follicular Lymphoma disease and also increase the length of response compared to the available standard combination chemotherapy treatment for Follicular Lymphoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Follicular Lymphoma
What is being tested?
Rituximab, Lenalidomide and Rituximab-CHOP
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,030 participants
Where
36 sitesin 2 countries
Study dates
29 Dec 2011to 30 Apr 2024
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed follicular lymphoma grade 1, 2 or 3a, Stage II-IV
  • Have no prior systemic treatment for lymphoma
  • Symptomatic follicular lymphoma requiring treatment.
  • Age ≥18 years
  • Eastern Cooperative oncology group performance status 0-2
  • Willing to follow pregnancy precautions

Who cannot join

  • Clinical evidence of transformed lymphoma or Grade 3b follicular lymphoma.
  • 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), human immunodeficiency virus (HIV)
  • Known sensitivity or allergy to murine products.
  • Presence or history of central nervous system involvement by lymphoma
  • At high risk for a venous thromboembolic event (VTE) and not willing to take VTE prophylaxis
Show all 10Show fewer
  • Any of the following laboratory abnormalities:
  • serum aspartate transaminase or alanine transaminase > 3x upper limit of normal (ULN), except in patients with documented liver involvement by lymphoma
  • total bilirubin > 2.0 mg/dl (34 µmol/L) except in cases of Gilberts Syndrome and documented liver or pancreatic involvement by lymphoma
  • creatinine clearance of < 30 mL/min

Trial locations and contacts

36 sites in 2 countries.

36 sites in 2 countries

United States26 sites

  • Local Institution - 50403

    Boston, Massachusetts, 02114

  • Local Institution - 50503

    Boston, Massachusetts, 02114

  • Local Institution - 54103

    Chandler, Arizona, 85224

  • Local Institution - 54403

    Cherry Hill, New Jersey, 08003

  • Local Institution - 50803

    Chicago, Illinois, 60657

  • Local Institution - 51603

    Colorado Springs, Colorado, 80909

  • Local Institution - 51203

    Dallas, Texas, 75246

  • Local Institution - 52503

    Englewood, Florida, 34223

  • Local Institution - 51803

    Fullerton, California, 92835

  • Local Institution - 53703

    Hackensack, New Jersey, 07601

  • Local Institution - 51103

    Houston, Texas, 77030

  • Local Institution - 52203

    Lexington, Kentucky, 40536

  • Local Institution - 52003

    Los Angeles, California, 90095

  • Local Institution - 54003

    Lubbock, Texas, 79410

  • Local Institution - 50903

    Morristown, New Jersey, 07960

  • Local Institution - 51303

    Nashville, Tennessee, 37203

  • Local Institution - 52403

    New York, New York, 10019

  • Local Institution - 50203

    New York, New York, 10021

  • Local Institution - 51703

    Orlando, Florida, 32806

  • Local Institution - 53303

    Richmond, Virginia, 23230

  • Local Institution - 52703

    Seattle, Washington, 98109

  • Local Institution - 53003

    Southfield, Michigan, 48075

  • Local Institution - 54303

    Sparta, New Jersey, 07871

  • Local Institution - 51003

    St Louis, Missouri, 63110

  • Local Institution - 53803

    St. Petersburg, Florida, 33705

  • Local Institution - 53603

    Westminster, Maryland, 21157

Other trials in United States

Japan10 sites

  • Local Institution - 40722

    Chuo-ku, Tokyo, 104-0045

  • Local Institution - 40922

    Fukuoka, 812-8582

  • Local Institution - 40422

    Hiroshima, 7200001

  • Local Institution - 40122

    Isehara City, Kanagawa, 259-1193

  • Local Institution - 40322

    Kobe, 650-0047

  • Local Institution - 40222

    Koto-ku, Tokyo, 1358550

  • Local Institution - 40622

    Kyoto, 602-8566

  • Local Institution - 41122

    Minato-ku, Tokyo, 105-8470

  • Local Institution - 41022

    Sendai, 983-8520

  • Local Institution - 40522

    Shizuoka, 410-2295

Other trials in Japan

About this study

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 in Subjects With Previously Untreated Follicular Lymphoma

The purpose of this study is to evaluate the effect of the combined treatment of lenalidomide and rituximab in controlling the Follicular Lymphoma disease and also increase the length of response compared to the available standard combination chemotherapy treatment for Follicular Lymphoma.

Read the 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.

The 'Relevance' cooperative group trial 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 Follicular Lymphoma patients enrolled in both studies will be analyzed.

Being tested
Rituximab, Lenalidomide, Rituximab-CHOP, Rituximab-CVP, Rituximab-Bendamustine
Keywords
Follicular lymphoma, Non-Hodgkins Follicular Lymphoma, treatment for Follicular Lymphoma, rituximab treatment, rituximab and lenalidomide treatment
Medical subject headings
Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RituximabDrug

    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.

  • LenalidomideDrug

    Also called Revlimid

    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-CHOPDrug

    7 to 8 weeks later responding patients will continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.

  • Rituximab-CVPDrug

    7 to 8 weeks later responding patients will continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.

  • Rituximab-BendamustineDrug

    7 to 8 weeks later responding patients will continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.

Study groups in NCT01476787
Study groupRoleWhat they receive
Lenalidomide + RituximabExperimental* Lenalidomide dose 20-mg on days 2-22 every 28 days for 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 up to 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.
Receives: Drug: Rituximab; Drug: Lenalidomide
ControlActive comparator• 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.
Receives: Drug: Rituximab-CHOP; Drug: Rituximab-CVP; Drug: Rituximab-Bendamustine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Complete Response Rate (CR/CRu) at 120 Weeks by Independent Central Review

    The Complete Response Rate (CR/CRu) is the percentage of participants who achieve complete response (CR/CRu) at 120 weeks as assessed per Independent Central Review.

    • Complete Response (CR): Disappearance of all evidence of disease.
    • Complete Response Unconfirmed (CRu): Disappearance of all disease with the exception of residual lymph nodes that are 1.5 cm or less in greatest transverse diameter and/or indeterminate bone marrow findings.

    Measured: At 120 weeks

  2. Progression-free Survival (PFS)

    Progression-free survival (PFS) is defined as the time from randomization into the study to the first observation of documented disease progression or death due to any cause.

    Progressive Disease (PD) is characterized by any of the following:

    • An increase of at least 50% in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal lymph node(s) or other disease sites.
    • The appearance of any new lesion during or after treatment.
    • An increase of at least 50% in the longest diameter of a previously identified node that was 1 cm or more in its short axis.
    • An increase of at least 50% in the size of other lesions (e.g., splenomegaly, hepatomegaly).

    Based on Kaplan-Meier estimates.

    Measured: From randomization into the study to the first observation of documented disease progression or death due to any cause (up to approximately 140 months).

Secondary outcomes (4)

  1. Complete Response Rate (CR) at 120 Weeks Per Independent Central Review

    The Complete Response Rate (CR) is the percentage of participants who achieve confirmed complete response (CR) at 120 weeks as assessed per Independent Central Review.

    • Complete Response (CR): Disappearance of all evidence of disease.

    Measured: At 120 weeks

  2. Event-free Survival (EFS)

    Event Free Survival (EFS) is defined as the time a participant remains free from certain negative events (disease progression, relapse, initiation of a new anti-lymphoma treatment, or death) between the date of randomization to the date of first documented progression, relapse, and initiation of a new anti-lymphoma treatment or death by any cause. Responding participants and those lost to follow up were censored at their last tumor assessment date.

    Progressive Disease (PD) is characterized by any of the following:

    • An increase of at least 50% in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal lymph node(s) or other disease sites.
    • The appearance of any new lesion during or after treatment.
    • An increase of at least 50% in the longest diameter of a previously identified node that was 1 cm or more in its short axis.
    • An increase of at least 50% in the size of other lesions (e.g., splenomegaly, hepatomegaly).

    Based on Kaplan-Meier estimates.

    Measured: From randomization to the date of first documented progression, relapse, and initiation of a new anti-lymphoma treatment or death by any cause (up to approximately 140 months).

  3. Overall Survival (OS)

    Overall survival (OS) is defined as the median length of time a participant stays alive from randomization. Participants who died, regardless of the cause of death, were considered to have had an event. Participants who withdrew consent for the study were considered censored at the time of withdrawal. Participants who completed the study and were still alive at the time of the clinical data cut-off date were censored. All participants who were lost to follow-up prior to the clinical data cut-off date were also considered censored at the time of last contact. Based on Kaplan-Meier estimates.

    Measured: From randomization to the date of death by any cause (up to approximately 144 months).

  4. Time to Next Anti-Lymphoma Treatment (TTNLT)

    Time to Next Lymphoma Treatment (TTNLT) was measured from the date of randomization to the date of the first documented administration of any new anti-lymphoma treatment (such as chemotherapy, radiotherapy, radio-immunotherapy, or immunotherapy). Participants who continued to respond to treatment or who were lost to follow-up were considered censored on their last visit date. Participants who died (due to any cause) before receiving a new anti-lymphoma treatment were included in the statistical analysis, with death being counted as an event. Based on Kaplan-Meier estimates.

    Measured: From the date of randomization to the date of the first documented administration of any new anti-lymphoma treatment (up to approximately 140 months).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Nov 2011 (estimated)
  2. Study start29 Dec 2011
  3. Primary completion30 Apr 2024
  4. Study completion30 Apr 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,030 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01476787
Sponsor's protocol ID
RV-FOL-GELARC-0683C
Other IDs
2011-002792-42
Acronym
RELEVANCE
Status last verified
Apr 2025
First submitted
18 Nov 2011
Last updated
14 May 2025
Data monitoring committee
Yes

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, 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.

    PubMed 30184451

  • Fowler NH, Davis RE, Rawal S, Nastoupil L, Hagemeister FB, McLaughlin P, Kwak LW, Romaguera JE, Fanale MA, Fayad LE, Westin JR, Shah J, Orlowski RZ, Wang M, Turturro F, Oki Y, Claret LC, Feng L, Baladandayuthapani V, Muzzafar T, Tsai KY, Samaniego F, Neelapu SS. Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma: an open-label, phase 2 trial. Lancet Oncol. 2014 Nov;15(12):1311-8. doi: 10.1016/S1470-2045(14)70455-3. Epub 2014 Oct 15.

    PubMed 25439689

  • Ahmadi T, Chong EA, Gordon A, Aqui NA, Nasta SD, Svoboda J, Mato AR, Schuster SJ. Combined lenalidomide, low-dose dexamethasone, and rituximab achieves durable responses in rituximab-resistant indolent and mantle cell lymphomas. Cancer. 2014 Jan 15;120(2):222-8. doi: 10.1002/cncr.28405. Epub 2013 Oct 7.

    PubMed 24122387

  • 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.

    PubMed 32673385

  • 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.

    PubMed 41915772

  • 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.

    PubMed 39374535

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Rituximab, Lenalidomide and Rituximab-CHOP in people with Follicular Lymphoma, run by Celgene at 36 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 36 sites in United States, Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete Response Rate (CR/CRu) at 120 Weeks by Independent Central Review (time frame: At 120 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01476787, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2025.

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