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

Sponsor

Celgene (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT01476787

Collaborator

The Lymphoma Academic Research Organisation (Other)

255

Enrollment

Locations

Arms

149.1

Anticipated Duration (Months)

5.4

Patients Per Site

Patients Per Site Per Month

Study Details

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

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 :

Dec 29, 2011

Anticipated Primary Completion Date :

Jun 1, 2024

Anticipated Study Completion Date :

Jun 1, 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 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 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.

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 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

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

Complete Response Rate (CR/CRu) at 120 weeks [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.
Progression free survival (PFS)Follicular lymphoma [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

Number of participants with adverse events [Up to 13 years]
Time to Treatment Failure (TTF)Follicular Lymphoma [Up to 13 years]
Time to Treatment Failure (TTF)Follicular Lymphoma
Number of Participants who Survive without an Event(s) [Up to 13 years]
Event Free Survival (EFS)Follicular Lymphoma
Time to Next Anti-Lymphoma Treatment (TTNLT) for Follicular Lymphoma [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
Time to Next Chemotherapy Treatment (TTNCT) for Follicular Lymphoma [Up to 13 years]
Time to Next Chemotherapy Treatment (TTNCT) for Follicular Lymphoma
Number of participants alive or dead [Up to 13 years]
Overall response by International Working Group (IWG) 1999 criteria [Up to 120 weeks]
Health related quality of life as measured by the EORTC QLQ-C30 for Follicular Lymphoma patients [Up to 13 years]
Health related quality of life as measured by the EORTC QLQ-C30 for Follicular Lymphoma patients
Event-Free Survival (EFS) [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.
Overall Survival (OS) [up to 12 years]
Will be measured from date of randomization to the date of death
Complete Response Rate (CR/CRu) at 120 weeks [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

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

	Site	City	State	Country	Postal Code
1	Ironwood Cancer and Research Center	Chandler	Arizona	United States	85224
2	Providence St Joseph Medical Center Cancer Center	Burbank	California	United States	91505
3	Compassionate Cancer Care Medical Group	Corona	California	United States	92829
4	Lalita Pandit, MD Inc.	Fountain Valley	California	United States	92708
5	Saint Jude Heritage Medical Center	Fullerton	California	United States	92835
6	Santa Monica Hematology Oncology	Los Angeles	California	United States	90095
7	Memorial Hospital	Colorado Springs	Colorado	United States	80909
8	Cancer Center of Central Connecticut	Southington	Connecticut	United States	06489
9	University Cancer Institute	Boynton Beach	Florida	United States	33426
10	Florida Cancer Specialists	Englewood	Florida	United States	34223
11	Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
12	Orlando Health, Inc	Orlando	Florida	United States	32806
13	Florida Cancer Specialists	Saint Petersburg	Florida	United States	33705
14	Advocate Illinois Masonic Medical Center	Chicago	Illinois	United States	60657
15	Kentucky Cancer Clinic	Hazard	Kentucky	United States	41701
16	University of Kentucky	Lexington	Kentucky	United States	40536
17	Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121-2483
18	Saint Joseph Medical Center	Westminster	Maryland	United States	21157
19	Mass General Hospital	Boston	Massachusetts	United States	02114
20	Newland Medical Associates, PC	Southfield	Michigan	United States	48075
21	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
22	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-6805
23	The Cancer Center at Hackensack University Medical Center	Cherry Hill	New Jersey	United States	08003
24	The Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
25	Hematology Oncology Associates of NJ	Morristown	New Jersey	United States	07960
26	Somerset Hematology-Oncology Associates	Somerset	New Jersey	United States	08873
27	The Cancer Center at Hackensack University Medical Center	Sparta	New Jersey	United States	07871
28	St. Luke's Roosevelt Hospital	New York	New York	United States	10019
29	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
30	Roger Maris Cancer Center	Fargo	North Dakota	United States	58122
31	Sarah Cannon Cancer Center	Nashville	Tennessee	United States	37203
32	Baylor Sammons Cancer Center	Dallas	Texas	United States	75246
33	MD Anderson Cancer Center	Houston	Texas	United States	77030
34	Joe Arrington Cancer Center	Lubbock	Texas	United States	79410
35	Virginia Cancer Institute	Richmond	Virginia	United States	23230
36	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
37	National Cancer Center Hospital	Chuo-ku		Japan	104-0045
38	Kyushu University Hospital	Higashi-ku, Fukuoka		Japan	812-8582
39	Chugoku Central Hospital	Hiroshima		Japan	7200001
40	Kobe City Medical Center General Hospital	Hyogo		Japan	650-0047
41	Tokai University School of Medicine	Isehara City, Kanagawa		Japan	259-1193
42	The Cancer Institute Hospital of Japanese Foundation For Cancer Research	Koto-ku		Japan	135-8550
43	University Hospital, Kyoto Prefectural University of Medicine	Kyoto-city		Japan	602-8566
44	Toranomon Hospital	Minato-ku		Japan	105-8470
45	Kurashiki Central Hospital	Okayama		Japan	710-8602
46	Sendai Medical Center	Sendai-city		Japan	983-8520
47	Juntendo University Shizuoka Hospital	Shizuoka		Japan	410-2295