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

Primary Purpose

Follicular Lymphoma

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Rituximab
Lenalidomide
Rituximab-CHOP
Rituximab-CVP
Rituximab-Bendamustine
Sponsored by
Celgene
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Follicular Lymphoma focused on measuring Follicular lymphoma, Non-Hodgkins Follicular Lymphoma, treatment for Follicular Lymphoma, rituximab treatment, rituximab and lenalidomide treatment

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Local Institution - 51203
  • Local Institution - 51103
  • Local Institution - 54003
  • Local Institution - 40222

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Lenalidomide + Rituximab

Control

Arm Description

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.

• 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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Number of participants with adverse events
Time to Treatment Failure (TTF)Follicular Lymphoma
Time to Treatment Failure (TTF)Follicular Lymphoma
Number of Participants who Survive without an Event(s)
Event Free Survival (EFS)Follicular Lymphoma
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
Time to Next Chemotherapy Treatment (TTNCT) for Follicular Lymphoma
Time to Next Chemotherapy Treatment (TTNCT) for Follicular Lymphoma
Number of participants alive or dead
Overall response by International Working Group (IWG) 1999 criteria
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
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.
Overall Survival (OS)
Will be measured from date of randomization to the date of death
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.

Full Information

First Posted
November 18, 2011
Last Updated
August 10, 2023
Sponsor
Celgene
Collaborators
The Lymphoma Academic Research Organisation
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1. Study Identification

Unique Protocol Identification Number
NCT01476787
Brief Title
Combined Rituximab and Lenalidomide Treatment for Untreated Patients With Follicular Lymphoma
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 29, 2011 (Actual)
Primary Completion Date
June 1, 2024 (Anticipated)
Study Completion Date
June 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene
Collaborators
The Lymphoma Academic Research Organisation

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Follicular Lymphoma
Keywords
Follicular lymphoma, Non-Hodgkins Follicular Lymphoma, treatment for Follicular Lymphoma, rituximab treatment, rituximab and lenalidomide treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
255 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lenalidomide + Rituximab
Arm Type
Experimental
Arm Description
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.
Arm Title
Control
Arm Type
Active Comparator
Arm Description
• 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.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
Revlimid
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Rituximab-CHOP
Intervention Description
7 to 8 weeks later responding patients will continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.
Intervention Type
Drug
Intervention Name(s)
Rituximab-CVP
Intervention Description
7 to 8 weeks later responding patients will continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.
Intervention Type
Drug
Intervention Name(s)
Rituximab-Bendamustine
Intervention Description
7 to 8 weeks later responding patients will continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.
Primary Outcome Measure Information:
Title
Complete Response Rate (CR/CRu) at 120 weeks
Description
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.
Time Frame
Up to approximately 2.5 years
Title
Progression free survival (PFS)Follicular lymphoma
Description
Is defined as the time from randomization into the study to the first observation of documented disease progression or death due to any cause.
Time Frame
Up to 12 years
Secondary Outcome Measure Information:
Title
Number of participants with adverse events
Time Frame
Up to 13 years
Title
Time to Treatment Failure (TTF)Follicular Lymphoma
Description
Time to Treatment Failure (TTF)Follicular Lymphoma
Time Frame
Up to 13 years
Title
Number of Participants who Survive without an Event(s)
Description
Event Free Survival (EFS)Follicular Lymphoma
Time Frame
Up to 13 years
Title
Time to Next Anti-Lymphoma Treatment (TTNLT) for Follicular Lymphoma
Description
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 Frame
Up to 12 years
Title
Time to Next Chemotherapy Treatment (TTNCT) for Follicular Lymphoma
Description
Time to Next Chemotherapy Treatment (TTNCT) for Follicular Lymphoma
Time Frame
Up to 13 years
Title
Number of participants alive or dead
Time Frame
Up to 13 years
Title
Overall response by International Working Group (IWG) 1999 criteria
Time Frame
Up to 120 weeks
Title
Health related quality of life as measured by the EORTC QLQ-C30 for Follicular Lymphoma patients
Description
Health related quality of life as measured by the EORTC QLQ-C30 for Follicular Lymphoma patients
Time Frame
Up to 13 years
Title
Event-Free Survival (EFS)
Description
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.
Time Frame
Up to 12 years
Title
Overall Survival (OS)
Description
Will be measured from date of randomization to the date of death
Time Frame
up to 12 years
Title
Complete Response Rate (CR/CRu) at 120 weeks
Description
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.
Time Frame
Up to approximately 2.5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Franck Morschhauser, MD, PhD
Organizational Affiliation
The Lymphoma Study Association (LYSA)
Official's Role
Study Chair
Facility Information:
Facility Name
Local Institution - 51203
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Local Institution - 51103
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Local Institution - 54003
City
Lubbock
State/Province
Texas
ZIP/Postal Code
79410
Country
United States
Facility Name
Local Institution - 40222
City
Koto-ku
State/Province
Tokyo
ZIP/Postal Code
1358550
Country
Japan

12. IPD Sharing Statement

Citations:
PubMed Identifier
30184451
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.
Results Reference
background
PubMed Identifier
25439689
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.
Results Reference
background
PubMed Identifier
24122387
Citation
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.
Results Reference
background
PubMed Identifier
32673385
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.
Results Reference
background
Links:
URL
https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Description
BMS Clinical Trial Information
URL
https://www.bmsstudyconnect.com/s/US/English/USenHome
Description
BMS Clinical Trial Patient Recruiting

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Combined Rituximab and Lenalidomide Treatment for Untreated Patients With Follicular Lymphoma

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