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

MANTLE CELL LYMPHOMA Clinical Trial

— MCL0208  

Official title:

A Phase III Multicenter, Randomized Study With Lenalidomide Maintenance vs Observation After Induction Regimen Containing Rituximab Followed by High Dose Chemotherapy and ASCT as First Line Treatment in Adult Patients With Advanced Mantle Cell Lymphoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02354313
• Other study ID #: IIL-MCL0208
• Secondary ID: 2009-012807-25
• Status: Active, not recruiting
• Phase: Phase 3
• First received: June 23, 2011
• Last updated: February 8, 2018
• Start date: May 2010
• Est. completion date: January 2019

Study information

• Verified date: February 2018
• Source: Fondazione Italiana Linfomi ONLUS
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 300
• Est. completion date: January 2019
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• MANTLE CELL LYMPHOMA

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
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	Firenze
Italy	Clinica Ematologica, A.O.U. San Martino - IST	Genova
Italy	Ematologia, A.O.U. San Martino	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	UO Ematologia Ospedale Dell'Angelo	Mestre	VE
Italy	Dipartimento di Ematologia e Oncologia - Ospedale Maggiore Policlinico Mangiagalli e Regina Elena	Milano
Italy	Divisione di Ematologia, Ospedale Niguarda	Milano
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	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
Portugal	Departemento de Hematologia di Instituto Português de Oncologia de Lisboa Francisco Gentil	Lisboa

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione Italiana Linfomi ONLUS

Countries where clinical trial is conducted

Italy,  Portugal, 

Outcome

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