Clinical trial NCT01476787: Combined Rituximab and Lenalidomide Treatment for Untreated Patients With 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 in Subjects With Previously Untreated Follicular Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Follicular Lymphoma
Keywords: Follicular lymphoma
Non-Hodgkins Follicular Lymphoma
treatment for Follicular Lymphoma
rituximab treatment
rituximab and lenalidomide treatment
Lead sponsor: Celgene
Sponsor class: INDUSTRY
Collaborators: name: The Lymphoma Academic Research Organisation
First posted: 2011-11-22
Enrollment: 1030
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* 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

Primary outcomes:
measure: Complete Response Rate (CR/CRu) at 120 Weeks by Independent Central Review
timeFrame: At 120 weeks
measure: Progression-free Survival (PFS)
timeFrame: 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:
measure: Complete Response Rate (CR) at 120 Weeks Per Independent Central Review
timeFrame: At 120 weeks
measure: Event-free Survival (EFS)
timeFrame: 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).
measure: Overall Survival (OS)
timeFrame: From randomization to the date of death by any cause (up to approximately 144 months).
measure: Time to Next Anti-Lymphoma Treatment (TTNLT)
timeFrame: From the date of randomization to the date of the first documented administration of any new anti-lymphoma treatment (up to approximately 140 months).
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Local Institution - 54103
state: Arizona
city: Fullerton
country: United States
facility: Local Institution - 51803
state: California
city: Los Angeles
country: United States
facility: Local Institution - 52003
state: California
city: Colorado Springs
country: United States
facility: Local Institution - 51603
state: Colorado
city: Englewood
country: United States
facility: Local Institution - 52503
state: Florida
city: Orlando
country: United States
facility: Local Institution - 51703
state: Florida
city: Saint Petersburg
country: United States
facility: Local Institution - 53803
state: Florida
city: Chicago
country: United States
facility: Local Institution - 50803
state: Illinois
city: Lexington
country: United States
facility: Local Institution - 52203
state: Kentucky
city: Westminster
country: United States
facility: Local Institution - 53603
state: Maryland
city: Boston
country: United States
facility: Local Institution - 50403
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 50503
state: Massachusetts
city: Southfield
country: United States
facility: Local Institution - 53003
state: Michigan
city: Saint Louis
country: United States
facility: Local Institution - 51003
state: Missouri
city: Cherry Hill
country: United States
facility: Local Institution - 54403
state: New Jersey
city: Hackensack
country: United States
facility: Local Institution - 53703
state: New Jersey
city: Morristown
country: United States
facility: Local Institution - 50903
state: New Jersey
city: Sparta
country: United States
facility: Local Institution - 54303
state: New Jersey
city: New York
country: United States
facility: Local Institution - 52403
state: New York
city: New York
country: United States
facility: Local Institution - 50203
state: New York
city: Nashville
country: United States
facility: Local Institution - 51303
state: Tennessee
city: Dallas
country: United States
facility: Local Institution - 51203
state: Texas
city: Houston
country: United States
facility: Local Institution - 51103
state: Texas
city: Lubbock
country: United States
facility: Local Institution - 54003
state: Texas
city: Richmond
country: United States
facility: Local Institution - 53303
state: Virginia
city: Seattle
country: United States
facility: Local Institution - 52703
state: Washington
city: Chuo-ku
country: Japan
facility: Local Institution - 40722
state: Tokyo
city: Koto-ku
country: Japan
facility: Local Institution - 40222
state: Tokyo
city: Minato-ku
country: Japan
facility: Local Institution - 41122
state: Tokyo
city: Fukuoka
country: Japan
facility: Local Institution - 40922
city: Hiroshima
country: Japan
facility: Local Institution - 40422
city: Isehara City, Kanagawa
country: Japan
facility: Local Institution - 40122
city: Kobe-city
country: Japan
facility: Local Institution - 40322
city: Kyoto-city
country: Japan
facility: Local Institution - 40622
city: Sendai-city
country: Japan
facility: Local Institution - 41022
city: Shizuoka
country: Japan
facility: Local Institution - 40522
Study officials:
affiliation: The Lymphoma Study Association (LYSA)
name: Franck Morschhauser, MD, PhD
role: STUDY_CHAIR
References:
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.
citation: 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.
citation: 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.
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.