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

NCT ID: NCT02354313

Last Updated: 2018-02-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2019-01-31

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

Conditions

MANTLE CELL LYMPHOMA

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lenalidomide

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

Group Type: EXPERIMENTAL

Lenalidomide

Intervention Type: 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.

Observation

no therapy is planned but only observation

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Lenalidomide

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.

Intervention Type: DRUG

Other Intervention Names

Revlimid

Eligibility Criteria

Inclusion Criteria

1. Any male or female adult with newly diagnosed mantle cell lymphoma according to the WHO criteria.

2. 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.

3. 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.

4. 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).

5. Measurable disease (two diameters) in at least one site. Osteoblastic bone lesions, ascites and pleural effusion are not considered measurable disease.

6. 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.

7. Be willing and able to comply with the protocol for the duration of the study.

8. 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)

9. 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.

10. All patients must have an understanding that the study drug could have a potential teratogenic risk. They must agree to abstain from donating blood while taking study drug therapy and following discontinuation of study drug therapy. They must to agree not to share study medication with another person. They must be counseled about pregnancy precautions and risks of fetal exposure.

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione Italiana Linfomi - ETS

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sergio Cortelazzo, MD

Role: STUDY_DIRECTOR

Humanitas Gavazzeni - Bergamo, Lombardia

Locations

UO Ematologia Ospedale Dell'Angelo

Mestre, VE, Italy

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

Alessandria, , Italy

AORN San G.Moscati

Avellino, , Italy

Centro di riferimento Oncologico - Oncologia Medica A

Aviano (PN), , Italy

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

Bologna, , Italy

Divisione di Ematologia e TMO, Ospedale di Bolzano

Bolzano, , Italy

Divisione di Ematologia Spedali Civili

Brescia, , Italy

Divisione di Ematologia Osp.Businco

Cagliari, , Italy

IRCC Onco-Ematologia

Candiolo, , Italy

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

Cuneo, , Italy

Divisione di Ematologia, Policlinico Careggi

Florence, , Italy

Ematologia, A.O.U. San Martino

Genova, , Italy

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

Genova, , Italy

Divisione di Ematologia Ospedale Vito Fazzi

Lecce, , Italy

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

Meldola (FC), , Italy

Ematologia AO Ospedali Riuniti Papardo-Piemonte

Messina, , Italy

Divisione di Ematologia, Ospedale Niguarda

Milan, , Italy

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

Milan, , Italy

Unità Linfomi- Dipartimento Oncoematologia- Istituto Scientifico San Raffaele IRCCS

Milan, , Italy

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

Mirano, , 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

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. 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

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

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

Pisa, , Italy

Divisione di Ematologia con TMO - Ospedale San Carlo

Potenza, , Italy

U.O di Ematologia Ospedale S. Maria delle Croci

Ravenna, , Italy

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

Reggio Calabria, , Italy

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

Reggio Emilia, , Italy

UO Ematologia - Ospedale degli Infermi

Rimini, , Italy

Cattedra di Ematologia Università Cattolica Policlinico Gemelli

Roma, , Italy

Dipartimento di Biotecnologie Cellulari ed Ematologia Università "La Sapienza"

Roma, , Italy

Divisione di Ematologia Policlinico Università Tor-Vergata

Roma, , Italy

Divisione di Oncologia Medica ed Ematologia, Istituto Clinico Humanitas

Rozzano (MI), , Italy

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

San Giovanni Rotondo, , Italy

Istituto di Ematologia - Azienda Ospedaliero Universitaria di Sassari

Sassari, , Italy

Divisione di Ematologia - Policlinico Le Scotte

Siena, , Italy

Struttura Complessa di Oncoematologia - Ospedale Santa Maria

Terni, , 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

U.O. Ematologia e Immunoematologia - Ospedale Cà Foncello

Treviso, , Italy

Divisione di Ematologia Ospedale Cardinale Panico

Tricase, , Italy

Ematologia Clinica Ospedale Maggiore

Trieste, , Italy

Clinica Ematologica ASUI Integrata di Udine

Udine, , Italy

Ospedale Policlinico G.B. Rossi

Verona, , Italy

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

Lisbon, , Portugal

Countries

Italy; Portugal

References

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Other Identifiers

2009-012807-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IIL-MCL0208

Identifier Type: -

Identifier Source: org_study_id