RELEVANCE: 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

Sponsor

The Lymphoma Academic Research Organisation (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01650701

Collaborator

Celgene Corporation (Industry)

1,030

Enrollment

Locations

Arms

151

Duration (Months)

29.4

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

1030 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 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.

Study Start Date :

Feb 1, 2012

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Sep 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lenalidomide + Rituximab 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, 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 • 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. Other Names: mabthera rituxan Drug: 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 Other Names: 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 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 Drug: 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, Drug: 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.

Arm

Intervention/Treatment

Experimental: Lenalidomide + Rituximab

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, 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

• 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.

Other Names:

mabthera

rituxan

Drug: 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

Other Names:

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

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

Drug: 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,

Drug: 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.

Outcome Measures

Primary Outcome Measures

COMPLETE RESPONSE RATE [Timeframe: CR/CRu rate at 120 weeks]
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.
Progression Free Survival (PFS) [up to 13 years]
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.

Secondary Outcome Measures

Number of participants with adverse events [up to13 years]
Time to Treatment Failure (TTF) [up to13 years]
Event Free Survival (EFS) [up to13 years]
Time to Next Anti-Lymphoma Treatment (TTNLT), [up to13 years]
Time to Next Chemotherapy Treatment (TTNCT) [up to13 years]
Overall Survival (OS) [up to13 years]
Overall response rate at 120 weeks by International Working Group (IWG) 1999 criteria [up to13 years]
Health related quality of life as measured by the EORTC QLQ-C30 [up to13 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

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