Phase III, Randomized Trial: Lenalidomide vs Observation After Induction With Rituximab Followed by Cht and ASCT in MCL Adult Patients

NCT02354313 | Unknown Phase 3

• 2 other identifiers: IIL-MCL02082009-012807-25
• Study Type: interventional
• Target: 300
• Locations: 2 countries
• Sites: 53

Brief Summary

A phase III multicenter, randomized study with Lenalidomide (Revlimid®) maintenance versus observation after intensified induction regimen containing rituximab followed by high dose chemotherapy and Autologous Stem Cell Transplantation as first line treatment in adult patients with advanced Mantle Cell Lymphoma: IIL study (MCL0208).

Conditions

MANTLE CELL LYMPHOMA

Keywords

MANTLE CELL LYMPHOMA (MCL); Lenalidomide (Len); Rituximab; ASCT; Revlimid; High dose chemotherapy; transplant

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS will be defined as the time between the date of randomization and the date of disease progression, relapse or death from any cause.therapy to prolong progression-free survival (PFS) after completion of first-line high-dose chemotherapy additioned with rituximab and followed by ASCT in adult patients with MCL who have achieved complete response (CR) or partial response (PR). PFS is defined according to Cheson et al (JCO, 2007) as the time from randomisation until lymphoma progression or death as a result of any cause.

  30 months from randomisation

Secondary Outcomes (8)

• Overall Survival (OS)

  36 months from randomisation (42 months from accrual)

• Progression Free Survival (PFS)

  36 months from accrual

• Disease-free survival (DFS)

  30 months from randomisation (36 months from accrual)

• Event-free survival (EFS)

  30 months from randomisation (36 months from accrual)

• Complete Response (CR) Rate

  up to 3 months from accrual

Study Arms (2)

Lenalidomide

EXPERIMENTAL

lenalidomide 10-15 mg once daily on days 1-21, every 28 day, for two years

Drug: Lenalidomide

Observation

NO INTERVENTION

no therapy is planned but only observation

Interventions

Lenalidomide DRUG

Treatment Phase: consisting in an induction phase (3 cycles of RCHOP, given every 21 days); consolidation phase: (high-dose cyclophosphamide (CTX), 2 cycles of high dose Ara-C, BEAM and ASCT). Randomization and maintenance phase: Patients who have achieved complete or partial response will be randomized between maintenance with lenalidomide or observation.

Also known as: Revlimid

Lenalidomide

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Any male or female adult with newly diagnosed mantle cell lymphoma according to the WHO criteria.
• Biopsy-proven mantle cell non-Hodgkin's lymphoma, including evidence of cyclin D1 overexpression or the translocation t(11;14)(q13;q32) by FISH or RT-PCR. In subjects whose tumors are negative for the cyclin D1, evidence of overexpression of cyclin D2 or D3 by immunohistochemistry will be acceptable.
• Age ≥18 years and \< 60 with ECOG performance status 0-3, or an age from 60 to 65 years with an ECOG performance status 0-2, except when PS impairment is related to NHL.
• Advanced stage (Stage III and IV according to Ann Arbor and stage II with bulky disease defined as a mass ≥ 5 cm or B symptoms).
• Measurable disease (two diameters) in at least one site. Osteoblastic bone lesions, ascites and pleural effusion are not considered measurable disease.
• Written informed consent prior to any study specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice.
• Be willing and able to comply with the protocol for the duration of the study.
• Females of childbearing potential (FCBP) must: have two negative medically supervised pregnancy test prior to starting of study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. This applies even if the patient practices complete and continued sexual abstinence. Either commit to continued abstinence from heterosexual intercourse (which must be reviewed on a monthly basis) or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting study drug, during the study therapy (including dose interruptions), and for 28 days after discontinuation of study therapy. The following are effective methods of contraception
• Implant
• Levonorgestrel-releasing intrauterine system (IUS)
• Medroxyprogesterone acetate depot
• Tubal sterilisation
• Sexual intercourse with a vasectomised male partner only; vasectomy must be confirmed by two negative semen analyses
• Ovulation inhibitory progesterone-only pills (i.e., desogestrel)
• Male patients must agree to use a condom during sexual contact with a FCBP, even if they have had a vasectomy, throughout study drug therapy, during any dose interruption and after cessation of study therapy. Agree to not donate semen during study drug therapy and for a period after end of study drug therapy.

You may not qualify if:

• Non-Hodgkin's lymphoma subtypes other than MCL
• Cytological variant with small cells with round nuclei mimicking CLL, which is frequently recognized in patients with a leukemic and splenomegaly presentation without or with minimal involvement of lymph nodes and has an indolent clinical course.
• History of malignancy other than squamous cell carcinoma, basal cell carcinoma of the skin or carcinoma in situ of the cervix, carcinoma in situ of the breast, incidental histological finding of prostate cancer (TNM stage of T1a or T1b) within the last 3 years.
• Major surgery, other than diagnostic surgery, within the last 4 weeks.
• Evidence of CNS involvement, patients with an history of uncontrolled seizures, central nervous system disorders or psychiatric disability considered by the Investigator to be clinically significant and adversely affecting compliance to study drugs. If clinically indicated, lumbar puncture, and MRI should be performed during the screening process.
• Clinically significant cardiac disease (VEF \<45%) (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 6 months (New York Heart Association Class III or IV heart disease) and marked impairment of pulmonary function (pulmonary diffusing capacity \<50%).
• Unacceptable hematologic values in the week prior to the start of study: hemoglobin \<9 g/dL, WBC \<3x109/L, platelets \<60x109/L, absolute neutrophil count (ANC)\<1.5x109/L (unless cytopenia is secondary to bone marrow involvement or autoimmune cytopenia related to lymphoma).
• Abnormal liver function tests, within one week prior to study start above any of the values listed: serum bilirubin \> 2 mg/dL, ALT or AST \>3 times the upper normal value; alkaline phosphatase\>2.5 times the upper normal value (unless these abnormalities are due to liver involvement of lymphoma).
• Abnormal renal function (serum creatinine \>2.0 mg/dL), unless it is disease related
• Patients with active opportunistic infections.
• Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible. Patients with HBcAb serology, will not be excluded from the study and be given lamivudine as prophylaxis starting one week before chemotherapy. HbsAg and AST/ALT ifHBV DNA is not available, will be monitored every three weeks. If HBV DNA is available, it will be monitored along with HBsAg
• Pregnant or lactating females

Sponsors & Collaborators

• Fondazione Italiana Linfomi - ETS: lead

Study Sites (53)

UO Ematologia Ospedale Dell'Angelo

Mestre, VE, Italy

Location

SC Ematologia A.O.SS. Biagio e Antonio e C. Arrigo

Alessandria, Italy

Location

AORN San G.Moscati

Avellino, Italy

Location

Centro di riferimento Oncologico - Oncologia Medica A

Aviano (PN), Italy

Location

Istituto di Ematologia ed Oncologia Medica A. Seragnoli Policlinico S. Orsola

Bologna, 40138, Italy

Location

Divisione di Ematologia e TMO, Ospedale di Bolzano

Bolzano, 39100, Italy

Location

Divisione di Ematologia Spedali Civili

Brescia, Italy

Location

Divisione di Ematologia Osp.Businco

Cagliari, Italy

Location

IRCC Onco-Ematologia

Candiolo, Italy

Location

S.C. di Ematologia e Trapianto di Midollo Osseo ASO S. Croce e Carle

Cuneo, Italy

Location

Divisione di Ematologia, Policlinico Careggi

Florence, Italy

Location

Ematologia, A.O.U. San Martino

Genova, 16132, Italy

Location

Clinica Ematologica, A.O.U. San Martino - IST

Genova, Italy

Location

Divisione di Ematologia Ospedale Vito Fazzi

Lecce, Italy

Location

Istituto Scientifico Romagnolo per lo studio e la cura dei Tumori-IRST - Meldola / Cesena

Meldola (FC), Italy

Location

Ematologia AO Ospedali Riuniti Papardo-Piemonte

Messina, Italy

Location

Divisione di Ematologia, Ospedale Niguarda

Milan, 20162, Italy

Location

Dipartimento di Ematologia e Oncologia - Ospedale Maggiore Policlinico Mangiagalli e Regina Elena

Milan, Italy

Location

Unità Linfomi- Dipartimento Oncoematologia- Istituto Scientifico San Raffaele IRCCS

Milan, Italy

Location

Dipartimento di Scienze Mediche UOC di Oncologia ed Ematologia Oncologica - Ospedale di Mirano

Mirano, Italy

Location

Dip. di Oncologia ed Ematologia - Università di Modena e Reggio Emilia Policlinico - COM Centro Oncologico Modenese

Modena, Italy

Location

Osp.San Gerardo Divisione di Ematologia

Monza, Italy

Location

S.C.D.U Ematologia Azienda Ospedaliera Universitaria Maggiore - Università del Piemonte Orientale

Novara, 28100, Italy

Location

U.O.C. Ematologia e CTMO Presidio Ospedale S. Francesco

Nuoro, Italy

Location

U.O. Oncoematologia Ospedale "Andrea Tortora"

Pagani, Italy

Location

Divisione di Ematologia, Azienda Ospedali Riuniti Villa Sofia Cervello

Palermo, Italy

Location

Oncoematologia e TMO Clinica "La Maddalena"

Palermo, Italy

Location

Cattedra di Ematologia - Centro Trapianti Midollo Osseo - Università Parma

Parma, Italy

Location

Fondazione Policlinico San Matteo Clinica Ematologica

Pavia, Italy

Location

U.O. Ematologia e Centro Trapianto Midollo Osseo - Ospedale G. da Saliceto

Piacenza, Italy

Location

Dipartimento di Oncologia Divisione di Ematologia, Azienda Ospedaliera Pisana Ospedale "S.Chiara"

Pisa, Italy

Location

Divisione di Ematologia con TMO - Ospedale San Carlo

Potenza, Italy

Location

U.O di Ematologia Ospedale S. Maria delle Croci

Ravenna, Italy

Location

Divisione di Ematologia - Presidio Ospedali Riuniti Bianchi, Melacrino, Morelli

Reggio Calabria, Italy

Location

S. C. Ematologia - Azienda Ospedaliera Arcispedale - "S.Maria Nuova" IRCCS

Reggio Emilia, Italy

Location

UO Ematologia - Ospedale degli Infermi

Rimini, Italy

Location

Cattedra di Ematologia Università Cattolica Policlinico Gemelli

Roma, Italy

Location

Dipartimento di Biotecnologie Cellulari ed Ematologia Università "La Sapienza"

Roma, Italy

Location

Divisione di Ematologia Policlinico Università Tor-Vergata

Roma, Italy

Location

Divisione di Oncologia Medica ed Ematologia, Istituto Clinico Humanitas

Rozzano (MI), Italy

Location

Divisione di Ematologia, Centro Trapianto di Cellule Staminali, IRCCS "Casa Sollievo della Sofferenza"

San Giovanni Rotondo, Italy

Location

Istituto di Ematologia - Azienda Ospedaliero Universitaria di Sassari

Sassari, Italy

Location

Divisione di Ematologia - Policlinico Le Scotte

Siena, Italy

Location

Struttura Complessa di Oncoematologia - Ospedale Santa Maria

Terni, Italy

Location

S.C.D.U. Ematologia Universitaria A.O. Città della Salute e della Scienza di Torino

Torino, Italy

Location

SC. Ematologia A.O. Città della Salute e della Scienza

Torino, Italy

Location

Divisione di Ematologia ASL BAT 1

Trani, Italy

Location

U.O. Ematologia e Immunoematologia - Ospedale Cà Foncello

Treviso, Italy

Location

Divisione di Ematologia Ospedale Cardinale Panico

Tricase, Italy

Location

Ematologia Clinica Ospedale Maggiore

Trieste, Italy

Location

Clinica Ematologica ASUI Integrata di Udine

Udine, Italy

Location

Ospedale Policlinico G.B. Rossi

Verona, Italy

Location

Departemento de Hematologia di Instituto Português de Oncologia de Lisboa Francisco Gentil

Lisbon, Portugal

Location

Related Publications (6)

• Ragaini S, Galli A, Genuardi E, Gandossini M, Alessandria B, Civita AM, Evangelista A, Amaducci E, Stefoni V, Cavallo F, Ballerini F, Puccini B, Vallisa D, Michieli M, Pascarella A, Palmas A, Patti C, Lucchini E, Careddu MG, Merli M, Postorino M, Boccomini C, Balzarotti M, Zilioli VR, Gomes da Silva M, Bruno B, Rizzo E, Ladetto M, Malcovati L, Ferrero S. Large clones of clonal hematopoiesis affect outcome in mantle cell lymphoma: results from the FIL MCL0208 clinical trial. Blood Adv. 2025 Apr 22;9(8):1805-1815. doi: 10.1182/bloodadvances.2024014948.

  PMID: 39808795 DERIVED

• Zaccaria GM, Ferrero S, Hoster E, Passera R, Evangelista A, Genuardi E, Drandi D, Ghislieri M, Barbero D, Del Giudice I, Tani M, Moia R, Volpetti S, Cabras MG, Di Renzo N, Merli F, Vallisa D, Spina M, Pascarella A, Latte G, Patti C, Fabbri A, Guarini A, Vitolo U, Hermine O, Kluin-Nelemans HC, Cortelazzo S, Dreyling M, Ladetto M. A Clinical Prognostic Model Based on Machine Learning from the Fondazione Italiana Linfomi (FIL) MCL0208 Phase III Trial. Cancers (Basel). 2021 Dec 31;14(1):188. doi: 10.3390/cancers14010188.

  PMID: 35008361 DERIVED

• Ladetto M, Cortelazzo S, Ferrero S, Evangelista A, Mian M, Tavarozzi R, Zanni M, Cavallo F, Di Rocco A, Stefoni V, Pagani C, Re A, Chiappella A, Balzarotti M, Zilioli VR, Gomes da Silva M, Arcaini L, Molinari AL, Ballerini F, Ferreri AJM, Puccini B, Benedetti F, Stefani PM, Narni F, Casaroli I, Stelitano C, Ciccone G, Vitolo U, Martelli M. Lenalidomide maintenance after autologous haematopoietic stem-cell transplantation in mantle cell lymphoma: results of a Fondazione Italiana Linfomi (FIL) multicentre, randomised, phase 3 trial. Lancet Haematol. 2021 Jan;8(1):e34-e44. doi: 10.1016/S2352-3026(20)30358-6. Epub 2020 Dec 22.

  PMID: 33357480 DERIVED

• Zaccaria GM, Ferrero S, Rosati S, Ghislieri M, Genuardi E, Evangelista A, Sandrone R, Castagneri C, Barbero D, Lo Schirico M, Arcaini L, Molinari AL, Ballerini F, Ferreri A, Omede P, Zamo A, Balestra G, Boccadoro M, Cortelazzo S, Ladetto M. Applying Data Warehousing to a Phase III Clinical Trial From the Fondazione Italiana Linfomi Ensures Superior Data Quality and Improved Assessment of Clinical Outcomes. JCO Clin Cancer Inform. 2019 Oct;3:1-15. doi: 10.1200/CCI.19.00049.

  PMID: 31633999 DERIVED

• Ferrero S, Rossi D, Rinaldi A, Bruscaggin A, Spina V, Eskelund CW, Evangelista A, Moia R, Kwee I, Dahl C, Di Rocco A, Stefoni V, Diop F, Favini C, Ghione P, Mahmoud AM, Schipani M, Kolstad A, Barbero D, Novero D, Paulli M, Zamo A, Jerkeman M, da Silva MG, Santoro A, Molinari A, Ferreri A, Gronbaek K, Piccin A, Cortelazzo S, Bertoni F, Ladetto M, Gaidano G. KMT2D mutations and TP53 disruptions are poor prognostic biomarkers in mantle cell lymphoma receiving high-dose therapy: a FIL study. Haematologica. 2020 Jun;105(6):1604-1612. doi: 10.3324/haematol.2018.214056. Epub 2019 Sep 19.

  PMID: 31537689 DERIVED

• Bomben R, Ferrero S, D'Agaro T, Dal Bo M, Re A, Evangelista A, Carella AM, Zamo A, Vitolo U, Omede P, Rusconi C, Arcaini L, Rigacci L, Luminari S, Piccin A, Liu D, Wiestner A, Gaidano G, Cortelazzo S, Ladetto M, Gattei V. A B-cell receptor-related gene signature predicts survival in mantle cell lymphoma: results from the Fondazione Italiana Linfomi MCL-0208 trial. Haematologica. 2018 May;103(5):849-856. doi: 10.3324/haematol.2017.184325. Epub 2018 Feb 22.

  PMID: 29472356 DERIVED

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

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

Intervention Hierarchy (Ancestors)

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

• Sergio Cortelazzo, MD

  Humanitas Gavazzeni - Bergamo, Lombardia

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: June 23, 2011
• First Posted: February 3, 2015
• Study Start: May 1, 2010
• Primary Completion: December 1, 2017
• Study Completion: January 1, 2019
• Last Updated: February 9, 2018

Record last verified: 2018-02

Locations

IT (52); PT (1)