Mantle Cell Lymphoma MedDRA version: 20.0 Level: PT Classification code 10061275 Term: Mantle cell lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
LYSARC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • signed informed consent form • Biopsy-proven mantle cell lymphoma according to WHO classification, including evidence of cyclin D1 overexpression or the translocation t(11;14)(q13;q32). • = 60 years of age and ineligible for autologous transplant • Ann Arbor stage II-IV • previously untreated • ECOG performance status = 2 • Male subjects must: - agree to use a condom during sexual contact with a woman of childbearing potential, even if they have had a vasectomy, throughout lenalidomide/placebo therapy - agree to not donate semen during lenalidomide therapy. • All subjects must: - have an understanding that the lenalidomide could have a potential teratogenic risk. - agree to abstain from donating blood while taking lenalidomide therapy - agree not to share study medication with another person. - be counseled about pregnancy precautions and risks of fetal exposure. • Additional criteria for randomization in maintenance phase : - CR, CRu or PR after induction treatment, determined as per Cheson 1999 criteria by investigator - During the run-in period of 6 months starting from the date of the first patient randomized in the trial: in case of direct randomization into maintenance phase, patient must have been treated in first line by 6-8 cycles of R-CHOP. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 183 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 450
Exclusion criteria
Exclusion criteria: • Female of child-bearing potential (without natural menopause for at least 24 consecutive months, a hysterectomy or bilateral oophorectomy) • Any of the following laboratory abnormalities, if not related to lymphoma: - Absolute neutrophils count (ANC) 3.0 x upper limit of normal. - Serum total bilirubin > 1.5 UNL (except if due to Gilbert’s syndrome) • Calculated creatinine clearance (Cockcroft-Gault formula or MDRD) < 30 mL /min. • Central nervous system involvement by lymphoma • Contraindication for medicamentous DVT prophylaxis • Prior history of malignancies other than MCL unless the subject has been free of the disease for = 5 years (Exceptions: Basal or squamous cell carcinoma of the skin, Carcinoma in situ of the cervix or of the breast, Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b). • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient to receive the study medication as planned. • Poor cardiac fuction (LVEF < 50%) on echecardiography • Seropositivity for human immunodeficiency virus (HIV, mandatory test) Seropositivity for hepatitis C virus (HCV, mandatory test), Active viral infection with hepatitis B virus (HBV, mandatory test): - HBsAg positive - HBsAg negative, anti-HBs positive and anti-HBc positive Patients with Prior Hepatitis B must be given antiviral prophylaxis and HBV DNA monitored. Note: Patients whore are HBsAg negative, anti HBs positive and/or anti HBc positive but viral DNA negative are eligible • Uncontrolled illness including, but not limited to: - Active infection requiring parenteral antibiotics - Uncontrolled diabetes mellitus - Chronic symptomatic congestive heart failure (Class NYHA III or IV). - Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months - Clinically significant cardiac arrhythmia that is symptomatic or requires treatment, or asymptomatic sustained ventricular tachycardia. • Prior = Grade 3 allergic hypersensitivity to thalidomide. • Prior = Grade 3 rash or any desquamating (blistering) rash while taking thalidomide. • Subjects with = Grade 2 neuropathy. • Known anti-murine antibody (HAMA) reactivity or known hypersensitivity to murine antibodies • Prior use of lenalidomide. • Participation in another clinical trial within three weeks before randomization in this study Additional exclusion criteria for randomization in maintenance phase: - SD or PD after induction treatment determined as per Cheson 1999 criteria assessed by investigator. - Patients who had not received at least 6 cycles of R-CHOP21 or 2 cycles of R-CHOP21 / 2 cycles of R-HAD28 (alternating) - Patients with serious underlying medical conditions, which could impair the ability to receive maintenance treatment - Calculated creatinine clearance (Cockcroft-Gault formula or MDRD) of < 30 mL /min at screening for maintenance. - ANC < 1,000 cells/mm³ (1.0 X 109/L) at screening for maintenance; - Platelet count < 50,000 cells/mm³ (50 X 109/L) at screening for maintenance.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the trial is to evaluate whether the addition of lenalidomide to standard rituximab-maintenance improves progression free survival (PFS) compared to standard rituximab maintenance after response to induction chemotherapy in older patients with mantle cell lymphoma not suitable for autologous stem cell transplantation ;Secondary Objective: The secondary efficacy objectives are: • to compare efficacy and safety of the maintenance regimens in terms of secondary endpoints • to evaluate whether the introduction of cytarabine into induction improves clinical outcome compared to standard R-CHOP in older patients with mantle cell lymphoma not suitable for autologous stem cell transplantation ;Primary end point(s): progression free survival (PFS).;Timepoint(s) of evaluation of this end point: From randomization for maintenance to progression or death from any cause. Tumor assessment (clinical examination, laboratory tests, CT scan, bone marrow examination) will be performed at baseline, at the end of induction and of maintenance and every 6 months during maintenance and follow-up period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Time to event - overall survival from induction randomization to death from any cause - overall survival from maintenance randomization to death from any cause - time to treatment failure, progression-free survival from induction randomization, remission duration - PR/CRu to CR and PR to CRu conversion during maintenance - Minimal residual disease (MRD) status and levels in peripheral blood and bone marrow at midterm and at the end of induction, after one and two years from end of induction and during follow-up until progression or up to 2.5 years of follow-up whichever comes first - complete and overall response rates (based on Cheson 1999 criteria) at midterm and end of induction, - safety according to NCI CTCAE (v 4.0) - secondary primary malignancies rates after lenalidomide vs. no lenalidomide - Exploratory : response assessment according to Cheson 2007 criteria including FDG-PET evaluation;Timepoint(s) of evaluation of this end point: • investigator-assessed progression free survival: from randomization for maintenance • overall survival: from first randomization to death from any cause • remission rates, time to treatment failure, remission duration: all duration of the study • minimal residual disease (MRD) levels: at end of induction, after one and two years of maintenance • safety according to NCI CTCAE (v 4.0): all duration of the study • PR to CR conversion: during maintenance • the rates of secondary neoplasias after lenalidomide vs. no lenalidomide: after starting maintenance treatment | — |
Countries
Belgium, France, Germany, Netherlands, Poland, Portugal, Spain
Contacts
Public ContactChristine STEPHAN
LYSARC
Outcome results
None listed