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

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 FOLLOWED BY RITUXIMAB IN SUBJECTS WITH PREVIOUSLY UNTREATED FOLLICULAR LYMPHOMA The "RELEVANCE" Trial (Rituximab Lenalidomide Versus ANy ChEmotherapy)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 Patients Enrolled in Both Studies Will be Analyzed.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01650701
• Other study ID #: RV-FOL-GELARC-0683
• Secondary ID: 2011-002792-42
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 2012
• Est. completion date: April 2024

Study information

• Verified date: March 2024
• Source: The Lymphoma Academic Research Organisation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1030
• Est. completion date: April 2024
• Est. primary completion date: May 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Follicular Lymphoma
• Lymphoma
• Lymphoma, Follicular

Intervention

Drug:
• Rituximab
• 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
• 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 - CHOP
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
• Rituximab - CVP
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,
• Rituximab - Bendamustine
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.

Locations

Country	Name	City	State
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Nepean Hospital	Penrith	New South Wales
Australia	Wollongong Hospital	Wollongong	New South Wales
Belgium	CHU Mont-Godinne	Yvoir
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Atlantic Health Sciences Corp - Saint John Regional Hospital	Halifax	Nova Scotia
Canada	Moncton Hospital	Moncton	New Brunswick
Canada	CHUM Hopital Notre-Dame	Montreal	Quebec
Canada	McGill University Department of Oncology	Montreal	Quebec
Canada	Hôpital de l'Enfant-Jesus, CHU de Quebec	Quebec city	Quebec
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Fraser Valley Cancer Centre	Surrey	British Columbia
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	UHN-Princess Margaret Hospital	Toronto	Ontario
Canada	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia
France	CHU Claude Huriez	Lille
Germany	Uniklinik Köln	Köln	Nordrhein
Germany	LMU Munchën - Klinikum Grosshadern	Munchen
Germany	Medizinische Klinik der Universität Tübingen	Tübingen	Baden Wurtemberg
Italy	Policlinico Sant'Orsola-Malpighi	Bologna
Italy	Sant'Andrea Hospital	Roma	Lazio
Portugal	Instituto Português Oncologia	Lisboa
Spain	Hospital Clínico de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario Vall d´Hebron	Barcelona
Spain	Institut Català d'Oncologia de Girona (ICO Girona)	Girona
Spain	Hospital Ramon y Cajal	Madrid
Spain	Hospital Costa del Sol	Marbella
Spain	Hospital Son Llatzer	Palma	Mallorca
Spain	Hospital Universitario Salamanca	Salamanca
Spain	Hospital Universitario de Canarias	Santa Cruz de Tenerife	Canarias
Spain	Hospital Virgen del Rocio	Sevilla	Andaloucia
Spain	Hospital Universitario Mutua de Terrassa	Terrassa	Barcelona
Spain	Hospital Clínico Universitario de Valencia	Valencia

Sponsors (2)

Lead Sponsor	Collaborator
The Lymphoma Academic Research Organisation	Celgene Corporation

Countries where clinical trial is conducted

Australia,  Belgium,  Canada,  France,  Germany,  Italy,  Portugal,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	COMPLETE RESPONSE RATE	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.	Timeframe: CR/CRu rate at 120 weeks
Primary	Progression Free Survival (PFS)	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.	up to 13 years
Secondary	Number of participants with adverse events		up to13 years
Secondary	Time to Treatment Failure (TTF)		up to13 years
Secondary	Event Free Survival (EFS)		up to13 years
Secondary	Time to Next Anti-Lymphoma Treatment (TTNLT),		up to13 years
Secondary	Time to Next Chemotherapy Treatment (TTNCT)		up to13 years
Secondary	Overall Survival (OS)		up to13 years
Secondary	Overall response rate at 120 weeks by International Working Group (IWG) 1999 criteria		up to13 years
Secondary	Health related quality of life as measured by the EORTC QLQ-C30		up to13 years