Combined Rituximab and Lenalidomide Treatment for Untreated Patients With Follicular Lymphoma

Follicular Lymphoma Clinical Trial

— RELEVANCE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01476787
• Other study ID #: RV-FOL-GELARC-0683C
• Secondary ID: 2011-002792-42
• Status: Completed
• Phase: Phase 3
• Start date: December 29, 2011
• Est. completion date: April 30, 2024

Study information

• Verified date: June 2024
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 255
• Est. completion date: April 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Follicular Lymphoma
• Lymphoma
• Lymphoma, Follicular

Intervention

Drug:
• 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.
• Lenalidomide
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-CHOP
7 to 8 weeks later responding patients will continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.
• Rituximab-CVP
7 to 8 weeks later responding patients will continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.
• Rituximab-Bendamustine
7 to 8 weeks later responding patients will continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.

Locations

Country	Name	City	State
Japan	Local Institution - 40722	Chuo-ku	Tokyo
Japan	Local Institution - 40922	Fukuoka
Japan	Local Institution - 40422	Hiroshima
Japan	Local Institution - 40122	Isehara City, Kanagawa
Japan	Local Institution - 40322	Kobe-city
Japan	Local Institution - 40222	Koto-ku	Tokyo
Japan	Local Institution - 40622	Kyoto-city
Japan	Local Institution - 41122	Minato-ku	Tokyo
Japan	Local Institution - 41022	Sendai-city
Japan	Local Institution - 40522	Shizuoka
United States	Local Institution - 51203	Dallas	Texas
United States	Local Institution - 51103	Houston	Texas
United States	Local Institution - 54003	Lubbock	Texas
United States	Local Institution - 53003	Southfield	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Celgene	The Lymphoma Academic Research Organisation

Countries where clinical trial is conducted

United States,  Japan, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Response Rate (CR/CRu) at 120 weeks	The tumor response data will be assessed by the IRC using the IWG (Cheson, 1999) criteria. Based on the CT/MRI schedule, any assessments in a time window of 120 weeks ± 4 weeks are qualified as the 120 week assessments.	Up to approximately 2.5 years
Primary	Progression free survival (PFS)Follicular lymphoma	Is defined as the time from randomization into the study to the first observation of documented disease progression or death due to any cause.	Up to 12 years
Secondary	Number of participants with adverse events		Up to 13 years
Secondary	Time to Treatment Failure (TTF)Follicular Lymphoma	Time to Treatment Failure (TTF)Follicular Lymphoma	Up to 13 years
Secondary	Number of Participants who Survive without an Event(s)	Event Free Survival (EFS)Follicular Lymphoma	Up to 13 years
Secondary	Time to Next Anti-Lymphoma Treatment (TTNLT) for Follicular Lymphoma	TTNLT will be measured from the date of randomization to the date of first documented administration of any new anti-lymphoma treatment (chemotherapy, radiotherapy, radio immunotherapy, immunotherapy). Patients continuing in response or who are lost to follow-up will be censored on their last visit date. Patients who died (due to any cause) before having received a new anti-lymphoma	Up to 12 years
Secondary	Time to Next Chemotherapy Treatment (TTNCT) for Follicular Lymphoma	Time to Next Chemotherapy Treatment (TTNCT) for Follicular Lymphoma	Up to 13 years
Secondary	Number of participants alive or dead		Up to 13 years
Secondary	Overall response by International Working Group (IWG) 1999 criteria		Up to 120 weeks
Secondary	Health related quality of life as measured by the EORTC QLQ-C30 for Follicular Lymphoma patients	Health related quality of life as measured by the EORTC QLQ-C30 for Follicular Lymphoma patients	Up to 13 years
Secondary	Event-Free Survival (EFS)	EFS will be measured from 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 patients and patients who are lost to follow up will be censored at their last tumor assessment date.	Up to 12 years
Secondary	Overall Survival (OS)	Will be measured from date of randomization to the date of death	up to 12 years
Secondary	Complete Response Rate (CR/CRu) at 120 weeks	The tumor response data will be assessed by the IRC using the IWG (Cheson, 1999) criteria. Based on the CT/MRI schedule, any assessments in a time window of 120 weeks ± 4 weeks are qualified as the 120 week assessments.	Up to approximately 2.5 years

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting