Combined Rituximab and Lenalidomide Treatment for Untreated Patients With Follicular Lymphoma (RELEVANCE)

• ClinicalTrials.gov Identifier: NCT01476787
• Recruitment Status: Active, not recruiting
• First Posted: November 22, 2011
• Last Update Posted: April 12, 2024
• Sponsor: Celgene
• Collaborator: The Lymphoma Academic Research Organisation
• Information provided by (Responsible Party): Celgene

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Follicular Lymphoma	Drug: Rituximab; Drug: Lenalidomide; Drug: Rituximab-CHOP; Drug: Rituximab-CVP; Drug: Rituximab-Bendamustine	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 255 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: December 29, 2011
• Estimated Primary Completion Date: April 30, 2024
• Estimated Study Completion Date: April 30, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Lenalidomide + Rituximab; 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.	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.; Drug: 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; Other Name: Revlimid
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.	Drug: Rituximab-CHOP; 7 to 8 weeks later responding patients will continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.; Drug: Rituximab-CVP; 7 to 8 weeks later responding patients will continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.; Drug: Rituximab-Bendamustine; 7 to 8 weeks later responding patients will continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.

Outcome Measures

Primary Outcome Measures :

1. Complete Response Rate (CR/CRu) at 120 weeks [ Time Frame: Up to approximately 2.5 years ]
   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.
2. Progression free survival (PFS)Follicular lymphoma [ Time Frame: Up to 12 years ]
   Is defined as the time from randomization into the study to the first observation of documented disease progression or death due to any cause.

Secondary Outcome Measures :

1. Number of participants with adverse events [ Time Frame: Up to 13 years ]
2. Time to Treatment Failure (TTF)Follicular Lymphoma [ Time Frame: Up to 13 years ]
   Time to Treatment Failure (TTF)Follicular Lymphoma
3. Number of Participants who Survive without an Event(s) [ Time Frame: Up to 13 years ]
   Event Free Survival (EFS)Follicular Lymphoma
4. Time to Next Anti-Lymphoma Treatment (TTNLT) for Follicular Lymphoma [ Time Frame: Up to 12 years ]
   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
5. Time to Next Chemotherapy Treatment (TTNCT) for Follicular Lymphoma [ Time Frame: Up to 13 years ]
   Time to Next Chemotherapy Treatment (TTNCT) for Follicular Lymphoma
6. Number of participants alive or dead [ Time Frame: Up to 13 years ]
7. Overall response by International Working Group (IWG) 1999 criteria [ Time Frame: Up to 120 weeks ]
8. Health related quality of life as measured by the EORTC QLQ-C30 for Follicular Lymphoma patients [ Time Frame: Up to 13 years ]
   Health related quality of life as measured by the EORTC QLQ-C30 for Follicular Lymphoma patients
9. Event-Free Survival (EFS) [ Time Frame: Up to 12 years ]

   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.

10. Overall Survival (OS) [ Time Frame: up to 12 years ]
    Will be measured from date of randomization to the date of death
11. Complete Response Rate (CR/CRu) at 120 weeks [ Time Frame: Up to approximately 2.5 years ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Michigan

Local Institution - 53003

Southfield, Michigan, United States, 48075

United States, Texas

Local Institution - 51203

Dallas, Texas, United States, 75246

Local Institution - 51103

Houston, Texas, United States, 77030

Local Institution - 54003

Lubbock, Texas, United States, 79410

Japan

Local Institution - 40222

Koto-ku, Tokyo, Japan, 1358550

Local Institution - 41022

Sendai-city, Japan, 983-8520

Sponsors and Collaborators

Celgene

The Lymphoma Academic Research Organisation

Investigators

• Study Chair: Franck Morschhauser, MD, PhD; The Lymphoma Study Association (LYSA)

More Information

Additional Information:

BMS Clinical Trial Information 

BMS Clinical Trial Patient Recruiting 

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.

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.

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.

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.

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT01476787
• Other Study ID Numbers: RV-FOL-GELARC-0683C; 2011-002792-42 ( EudraCT Number )
• First Posted: November 22, 2011
• Last Update Posted: April 12, 2024
• Last Verified: April 2024

Keywords provided by Celgene:

Follicular lymphoma; Non-Hodgkins Follicular Lymphoma; treatment for Follicular Lymphoma; rituximab treatment; rituximab and lenalidomide treatment

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Follicular; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Rituximab; Lenalidomide; Bendamustine Hydrochloride; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action