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

Phase 3

• Conditions: MANTLE CELL LYMPHOMA
• Interventions: Drug: Lenalidomide

• Registration Number: NCT02354313
• Lead Sponsor: Fondazione Italiana Linfomi - ETS

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).

Detailed Description

This is a Phase 3, multicenter, open-label, randomized, controlled study to determine the efficacy and safety of lenalidomide as maintenance therapy versus observation in patients with MCL in complete or partial remission after first line intensified and high-dose chemotherapy additioned with rituximab and followed by ASCT. This study will be conducted in three phases: a Screening Phase, a Treatment Phase and a Follow-up Phase

Study Timeline

• Study Start: 2010-05
• Study First Submitted: 2011-06-23
• Study First Submitted QC: 2015-02-02
• Study First Posted: 2015-02-03
• Primary Completion: 2017-12
• Status Verified: 2018-02
• Last Update Submitted: 2018-02-08
• Last Update Posted: 2018-02-09
• Study Completion: 2019-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

Not provided

Exclusion Criteria

1. Non-Hodgkin's lymphoma subtypes other than MCL
2. 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.
3. 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.
4. Major surgery, other than diagnostic surgery, within the last 4 weeks.
5. 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.
6. 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%).
7. 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).
8. 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).
9. Abnormal renal function (serum creatinine >2.0 mg/dL), unless it is disease related
10. Patients with active opportunistic infections.
11. 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
12. Pregnant or lactating females

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	30 months from randomisation	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	36 months from randomisation (42 months from accrual)	OS will be defined as the time between the date of randomization and the date of death from any cause
Disease-free survival (DFS)	30 months from randomisation (36 months from accrual)	DFS will be defined in CR patients as the time between the date of randomization and the date of relapse or death as a result of lymphoma or acute toxicity of treatment according to the Cheson 2007
Complete Response (CR) Rate	up to 3 months from accrual	Proportion of CR according to the Cheson 2007 response criteria
Overall Response Rate (ORR)	up to 3 months from accrual	ORR is defined as Complete Response (CR) or Partial Response (PR) according to the Cheson 2007 response criteria
Progression Free Survival (PFS)	36 months from accrual	PFS will be defined as the time between the date of enrolment and the date of disease progression, relapse or death from any cause.
Event-free survival (EFS)	30 months from randomisation (36 months from accrual)	EFS will be defined in CR patients as the time between the date of randomization and the date of failure of treatment or death as a result of any cause according to the Cheson 2007
Incidence of grade 3 or higher Toxicity measured by CTCAE v.4 at any time during therapy and follow-up.	30 months from accrual	Toxicity amount of grade 3 or more as CTCAE
Quality of life	baseline, 6-12-18-24 months from randomisation	EORTC QLQC30 questionnaire

Trial Locations

Locations (53)

AORN San G.Moscati; 🇮🇹 Avellino, Italy

UO Ematologia Ospedale Dell'Angelo; 🇮🇹 Mestre, VE, Italy

Divisione di Ematologia, Policlinico Careggi; 🇮🇹 Firenze, Italy

Clinica Ematologica ASUI Integrata di Udine; 🇮🇹 Udine, Italy

IRCC Onco-Ematologia; 🇮🇹 Candiolo, Italy

Divisione di Ematologia e TMO, Ospedale di Bolzano; 🇮🇹 Bolzano, Italy

Divisione di Ematologia, Ospedale Niguarda; 🇮🇹 Milano, Italy

Divisione di Ematologia Spedali Civili; 🇮🇹 Brescia, Italy

Istituto Scientifico Romagnolo per lo studio e la cura dei Tumori-IRST - Meldola / Cesena; 🇮🇹 Meldola (FC), Italy

Departemento de Hematologia di Instituto Português de Oncologia de Lisboa Francisco Gentil; 🇵🇹 Lisboa, Portugal

Divisione di Ematologia Ospedale Vito Fazzi; 🇮🇹 Lecce, Italy

Cattedra di Ematologia - Centro Trapianti Midollo Osseo - Università Parma; 🇮🇹 Parma, Italy

Fondazione Policlinico San Matteo Clinica Ematologica; 🇮🇹 Pavia, Italy

U.O. Ematologia e Centro Trapianto Midollo Osseo - Ospedale G. da Saliceto; 🇮🇹 Piacenza, Italy

S. C. Ematologia - Azienda Ospedaliera Arcispedale - "S.Maria Nuova" IRCCS; 🇮🇹 Reggio Emilia, Italy

UO Ematologia - Ospedale degli Infermi; 🇮🇹 Rimini, Italy

Centro di riferimento Oncologico - Oncologia Medica A; 🇮🇹 Aviano (PN), Italy

S.C. di Ematologia e Trapianto di Midollo Osseo ASO S. Croce e Carle; 🇮🇹 Cuneo, Italy

Clinica Ematologica, A.O.U. San Martino - IST; 🇮🇹 Genova, Italy

S.C.D.U Ematologia Azienda Ospedaliera Universitaria Maggiore - Università del Piemonte Orientale; 🇮🇹 Novara, Italy

U.O.C. Ematologia e CTMO Presidio Ospedale S. Francesco; 🇮🇹 Nuoro, Italy

U.O di Ematologia Ospedale S. Maria delle Croci; 🇮🇹 Ravenna, Italy

Dipartimento di Biotecnologie Cellulari ed Ematologia Università "La Sapienza"; 🇮🇹 Roma, Italy

Divisione di Ematologia, Centro Trapianto di Cellule Staminali, IRCCS "Casa Sollievo della Sofferenza"; 🇮🇹 San Giovanni Rotondo, Italy

S.C.D.U. Ematologia Universitaria A.O. Città della Salute e della Scienza di Torino; 🇮🇹 Torino, Italy

SC. Ematologia A.O. Città della Salute e della Scienza; 🇮🇹 Torino, Italy

Divisione di Ematologia ASL BAT 1; 🇮🇹 Trani, Italy

Ospedale Policlinico G.B. Rossi; 🇮🇹 Verona, Italy

SC Ematologia A.O.SS. Biagio e Antonio e C. Arrigo; 🇮🇹 Alessandria, Italy

Istituto di Ematologia ed Oncologia Medica A. Seragnoli Policlinico S. Orsola; 🇮🇹 Bologna, Italy

Ematologia, A.O.U. San Martino; 🇮🇹 Genova, Italy

Divisione di Ematologia Osp.Businco; 🇮🇹 Cagliari, Italy

Ematologia AO Ospedali Riuniti Papardo-Piemonte; 🇮🇹 Messina, Italy

Unità Linfomi- Dipartimento Oncoematologia- Istituto Scientifico San Raffaele IRCCS; 🇮🇹 Milano, Italy

Dipartimento di Scienze Mediche UOC di Oncologia ed Ematologia Oncologica - Ospedale di Mirano; 🇮🇹 Mirano, Italy

Dipartimento di Ematologia e Oncologia - Ospedale Maggiore Policlinico Mangiagalli e Regina Elena; 🇮🇹 Milano, Italy

Dip. di Oncologia ed Ematologia - Università di Modena e Reggio Emilia Policlinico - COM Centro Oncologico Modenese; 🇮🇹 Modena, Italy

Osp.San Gerardo Divisione di Ematologia; 🇮🇹 Monza, Italy

U.O. Oncoematologia Ospedale "Andrea Tortora"; 🇮🇹 Pagani, Italy

Divisione di Ematologia, Azienda Ospedali Riuniti Villa Sofia Cervello; 🇮🇹 Palermo, Italy

Oncoematologia e TMO Clinica "La Maddalena"; 🇮🇹 Palermo, Italy

Dipartimento di Oncologia Divisione di Ematologia, Azienda Ospedaliera Pisana Ospedale "S.Chiara"; 🇮🇹 Pisa, Italy

Divisione di Ematologia con TMO - Ospedale San Carlo; 🇮🇹 Potenza, Italy

Cattedra di Ematologia Università Cattolica Policlinico Gemelli; 🇮🇹 Roma, Italy

Divisione di Ematologia - Presidio Ospedali Riuniti Bianchi, Melacrino, Morelli; 🇮🇹 Reggio Calabria, Italy

Divisione di Ematologia Policlinico Università Tor-Vergata; 🇮🇹 Roma, Italy

Divisione di Oncologia Medica ed Ematologia, Istituto Clinico Humanitas; 🇮🇹 Rozzano (MI), Italy

Struttura Complessa di Oncoematologia - Ospedale Santa Maria; 🇮🇹 Terni, Italy

Divisione di Ematologia - Policlinico Le Scotte; 🇮🇹 Siena, Italy

Istituto di Ematologia - Azienda Ospedaliero Universitaria di Sassari; 🇮🇹 Sassari, Italy

U.O. Ematologia e Immunoematologia - Ospedale Cà Foncello; 🇮🇹 Treviso, Italy

Ematologia Clinica Ospedale Maggiore; 🇮🇹 Trieste, Italy

Divisione di Ematologia Ospedale Cardinale Panico; 🇮🇹 Tricase, Italy