Rituximab and Lenalidomide vs Rituximab Alone as Maintenance After R-chemoterapy for Relapsed/Refractory FL Patients

NCT02390869 | Active Not Recruiting Phase 3

• 1 other identifier: FIL_RENOIR12
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 28

Brief Summary

A randomized phase III multicenter trial assessing efficacy and toxicity of a combination of Rituximab and Lenalidomide (R2) vs Rituximab alone as maintenance after chemoimmunotherapy with Rituximab-chemotherapy (R-CHT) for relapsed/refractory FL patients not eligible for autologous transplantation (ASCT)

Conditions

Lymphoma, Follicular

Keywords

relapse/refractory

Outcome Measures

Primary Outcomes (1)

• PFS

  Progression-free survival

  2 years from randomization

Secondary Outcomes (7)

• OS

  2 years from randomization

• Toxicity (Common Terminology Criteria for Adverse Event version 4.03 (CTCAE)

  2 years from randomization

• Rate of molecular remission

  2 years from randomization

• Rate of molecular conversion

  2 years from randomization

• Rate of molecular relapse

  2 years from randomization

Study Arms (2)

R2-MANT

EXPERIMENTAL

A) Rituximab B) Lenalidomide

Drug: R2-MANT

R-MANT

ACTIVE COMPARATOR

A) Rituximab

Drug: R-MANT

Interventions

R2-MANT DRUG

A) Rituximab 375 mg/sqm on day 1 every 90 days for 8 cycles B) Lenalidomide (10 mg daily on days 1-21 every 28 days) for 24 cycles

Also known as: Rituximab and Lenalidomide (R2)

R2-MANT

R-MANT DRUG

A) Rituximab 375 mg/sqm on day 1 every 90 days for 8 cycles

Also known as: Rituximab (R)

R-MANT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Follicular lymphoma grade I, II and IIIa according to the WHO classification. Rebiopsy at study entry is strongly encouraged but mandatory only in case of suspected transformation (elevated LDH or rapidly-growing disease or unusual relapse presentation).
• First or second relapse or progression following R-chemotherapy (Rituximab maintenance and IF radiotherapy are not considered treatment lines).
• Previous treatment with Bendamustine can be considered eligible if relapse occurred after ≥ 24 months.
• Age \>18 years.
• Patients not eligible for high dose chemotherapy and ASCT because of: age ≥ 65 years, impaired PS or organ function due to major comorbidities or relapsed or refractory disease after previous ASCT before 65 of age.
• Stage II, III or IV according to Ann Arbor at relapse.
• Need of treatment according to SIE-SIES-GITMO guidelines for follicular lymphoma: stage II-IV with systemic symptoms, high tumor burden (i.e. \>3 lymph nodes measuring \>3 cm or a single lymph node \>7 cm), extranodal disease, cytopenia due to marrow involvement, spleen involvement (≥16 cm by CT), leukemic phase, serious effusion, symptomatic or life endangering organ involvement, rapid lymphoma progression, consistently increased LDH levels.
• Must be able to adhere to the study visit schedule and other protocol standards.
• ECOG performance status ≤ 2 (except when PS impairment is related to lymphoma).
• Be willing and able to comply with the protocol for the duration of the study.
• Absolute neutrophil count (ANC) ≥ 1.5 x 10 9/L unless due to marrow involvement by lymphoma; and platelets count ≥ 75 x 109/L unless due to marrow involvement by lymphoma.
• Calculated creatinine clearances ≥ 40 ml/min.
• Agree to be using effective contraception for the entire treatment period according to standard guidelines for patients receiving lenalidomide

You may not qualify if:

• Any lymphoma subtype other than FL including transformed FL
• Grade 3b follicular lymphoma.
• Radiotherapy within 3 months prior to study entry
• Major surgery (excluding lymph node biopsy) within 28 days prior to registration.
• HIV positive serology. HBV and HCV positive patients will be not excluded from the study if the hepatic enzymes are within the ranges later defined. HBV occult carriers patients will be given lamivudine as prophylaxis starting one week before chemotherapy. HbsAg, HBcAb, HBV-DNA and HCV-RNA levels will be monitored twice every month in HCV or HBV positive patients.
• Life expectancy \< 6 months.
• Known sensitivity or allergy to murine products.
• Prior history of malignancies, other than follicular lymphoma, unless the subject has been free of the disease for \> 3 years with the exception of adequately cured localized non-melanoma skin cancer, carcinoma in situ of the cervix, carcinoma in situ of the breast or incidental histological finding of prostate cancer (TNM stage of T1a or T1b)
• Prior use of lenalidomide.
• Neuropathy \> Grade 1.
• Myocardial infarction within the last 6 months
• Presence or history of CNS involvement by lymphoma.
• Subjects 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 subjects with documented liver involvement by lymphoma
• Total bilirubin \> 2.0 mg/dl (34 umol/L) except in cases of Gilberts Syndrome and documented liver involvement by lymphoma

Sponsors & Collaborators

• Fondazione Italiana Linfomi - ETS: lead

Study Sites (28)

ASST Grande Ospedale Metropolitano Niguarda

Milan, MI, 20162, Italy

Location

AUSL di Ravenna

Ravenna, RA, 48100, Italy

Location

Fondazione Del Piemonte Per L'Oncologia Ircc Di Candiolo

Candiolo, Torino, 10060, Italy

Location

Ospedale S. Giacomo di Castelfranco Veneto

Castelfranco Veneto, Treviso, 31033, Italy

Location

A.O. S. Maria di Terni

Terni, TR, 05100, Italy

Location

ASST Valle Olona - Ospedale di Circolo di Busto Arsizio

Busto Arsizio, Varese, Italy

Location

Ospedale SS Antonio Biagio e Cesare Arrigo

Alessandria, Italy

Location

Ospedale C. e G. Mazzoni UOS Ematologia

Ascoli Piceno, Italy

Location

Centro di riferimento Oncologico - Oncologia Medica A

Aviano (PN), Italy

Location

SOS Ematologia Divisione Medicina Interna Ospedale degli Infermi

Biella, Italy

Location

Divisione di Ematologia Spedali Civili

Brescia, Italy

Location

A.O. Universitaria Ospedale Vittorio Emanuele E Ferrarotto Di Catania

Catania, 95124, Italy

Location

AO Santa Croce e Carle

Cuneo, 12100, Italy

Location

A.O. Universitaria Careggi Di Firenze

Florence, 50139, Italy

Location

A.S.L. 9 Opsedali Riuniti del Canavese

Ivrea, Italy

Location

Area Vasta Romagna e IRST

Meldola (FC), Italy

Location

A O Papardo

Messina, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy

Location

A.O. Universitaria Policlinico Di Modena

Modena, 41124, Italy

Location

AOU Maggiore della Carità di Novara

Novara, 28100, Italy

Location

IRCCS Istituto Oncologico Veneto -Oncologia 1

Padua, Italy

Location

Ausl Di Piacenza

Piacenza, 29121, Italy

Location

AO Arcispedale S.Maria Nuova Ematologia

Reggio Emilia, Italy

Location

AOU La Sapienza

Roma, 00161, Italy

Location

Nuovo Ospedale Civile di Sassuolo - Day Hospital Oncologico

Sassuolo, Italy

Location

A.O. Universitaria Citta' Della Salute E Della Scienza Di Torino

Torino, 10126, Italy

Location

A.O.U. Citta della Salute e della Scienza di Torino - Ematologia Universitaria

Torino, Italy

Location

Ematologia - OSPEDALE DI CIRCOLO E FONDAZIONE MACCHI

Varese, 21100, Italy

Location

MeSH Terms

Conditions

Lymphoma, Follicular; Recurrence

Interventions

Rituximab; Lenalidomide

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Umberto Vitolo, MD

  Candiolo Cancer Institute, FPO-IRCCS

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2015
• First Posted: March 18, 2015
• Study Start: May 1, 2014
• Primary Completion: January 25, 2023
• Study Completion (Estimated): August 1, 2027
• Last Updated: December 2, 2025

Record last verified: 2025-12

Locations

IT (28)