Diffuse Large B Cell Lymphoma MedDRA version: 20.0 Level: PT Classification code 10012818 Term: Diffuse large B-cell lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: REVLIMID 25mg
Product Name: REVLIMID
Pharmaceutical Form: Capsule
INN or Proposed INN: LENALIDOMIDE
Other descriptive name:
Sponsors
LYSARC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - For patients registered at the time of initial diagnosis: • Patient with histologically proven CD20+ diffuse large B-cell lymphoma (DLBCL) (WHO classification 2008) including clinical subtypes (primitive mediastinal, intravascular, etc.). Patients with De Novo Transformed DLBCL from low grade lymphoma (Follicular, other..) may also be included. Patients with DLBCL associated with some small cell infiltration in bone marrow may also be included - Or CD20+ B-cell lymphoma with intermediate features between DLBCL and Burkitt or with intermediate features between DLBCL and classical Hodgkin lymphoma - Or CD20+ Follicular lymphoma grade 3B - Or CD20+ Agressive B-cell lymphoma unclassifiable • Previously untreated with chemo- or radiotherapy - For patients registered after response evaluation to first line treatment with R-CHOP: • Patient with histologically proven CD20+ diffuse large B-cell lymphoma (DLBCL) (WHO classification 2008) including clinical subtypes (primitive mediastinal, intravascular, etc.). Patients with De Novo Transformed DLBCL from low grade lymphoma (Follicular, other...) may also be included. Patients with DLBCL associated with some small cell infiltration in bone marrow may also be included - Or CD20+ B-cell lymphoma with intermediate features between DLBCL and Burkitt or with intermediate features between DLBCL and classical Hodgkin lymphoma - Or CD20+ Follicular lymphoma grade 3B - Or CD20+ Agressive B-cell lymphoma unclassifiable • Have reached a CR or PR (Cheson 2007) after first line treatment with at least 6 cycles of R-CHOP-14 regimens and up to 8 cycles of R-CHOP-21 • Previously untreated with Radiotherapy For all patients: • Aged from 60 to 80 years at time of registration • Ann Arbor stages II-IV at time of initial diagnosis • aaIPI = 1 at time of initial diagnosis • Eastern Cooperative Oncology Group [ECOG] performance status 0-2 • Minimum life expectancy of 3 months • Voluntary signed informed consent before performance of any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care. • The following laboratory values at screening - Absolute neutrophil count (ANC) = 1 000.106/L and Platelets = 60 000.106/L, unless these abnormalities are related to bone marrow infiltration. - Aspartate transaminase (AST) = 5 x ULN; Alanine transaminase (ALT) = 5 x ULN; Total bilirubin = 1.5 x ULN; - Creatinine clearance > 30 ml/min (as calculated by the Cockcroft- Gault formula) • Females of childbearing potential (FCBP)† must: - Have a 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 intercours
Exclusion criteria
Exclusion criteria: For all patients: 1- Any other histological type of lymphoma, Burkitt included. 2- Any history of treated or non-treated small B-cell lymphoma 3- Central nervous system or meningeal involvement by lymphoma 4- Contraindication to any drug contained in the chemotherapy regimen For example: "cardiac contra-indication to anthracyclines (alteration of Left Ventricular Function defined by LVEF<50%) neurological contraindication to vincristine (peripheral neuropathy of WHO grade = 2). 5- Myocardial infarction during last 3 months or unstable coronary disease or uncontrolled chronic symptomatic congestive heart insufficiency NYHA III - IV 6- Uncontrolled hypertension 7- Uncontrolled diabetes mellitus as defined by the investigator 8- Active systemic infection requiring treatment. 9- Previously known HIV positive serology 10- Active hepatitis B or C 11- Prior history of malignancies other than lymphoma within 3 years (except for complete resection of basal cell carcinoma, squamous cell carcinoma of the skin, or in situ malignancy. Patients previously diagnosed with prostate cancer are eligible if (1) their disease was T1-T2a, N0, M0, with a Gleason score = 7, and a prostate specific antigen (PSA) = 10 ng/mL prior to initial therapy, (2) they had definitive curative therapy (ie, prostatectomy or radiotherapy) = 2 years before Day 1 of Cycle 1, and (3) at a minimum 2 years following therapy they had no clinical evidence of prostate cancer, and their PSA was undetectable if they underwent prostatectomy or <1 ng/mL if they did not undergo prostatectomy. 12- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to determine the benefit estimated by the progression-free survival associated with lenalidomide maintenance compared to placebo in responding patients treated with R-CHOP for diffuse large B-cell lymphoma.; Secondary Objective: The secondary objectives are to assess: • percentage of patients who convert from PR to CR • efficacy according to the response to R-CHOP • Overall survival in both groups of patients (with and without lenalidomide maintenance) • The safety of lenalidomide in maintenance ; Primary end point(s): The primary endpoint is the progression-free survival (PFS) associated with lenalidomide maintenance compared to placebo in responding patients treated with R-CHOP for diffuse large B cell lymphoma. PFS will be measured from the date of randomization to the date of first documented disease progression or death.Progression data will be assigned to the earliest time when any progression is observed without prior missing assessments during the study up to the end of the follow up phase. ; Timepoint(s) of evaluation of this end point: The final PFS analysis will be realized when a total of 160 progression/death has been reached. The approximate updated schedule of the final analysis will be 90 months (September 2016 after the first patient randomized. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary end points are: - Overall survival (OS) in both groups of patients (lenalidomide or placebo) - Event-Free Survival (EFS) - Progression Free Survival 2 (PFS2) : Time from randomization to objective tumor progression on next-line treatment or death from any cause - Response rate at the end of maintenance treatment - Percentage of patients who convert from PR (partial response) to CR (complete response) - Safety of lenalidomide in maintenance ; Timepoint(s) of evaluation of this end point: - OS, EFS and PFS2 : interim analysis at the time of final analysis of PFS, final analysis at the study closure. - Response rate at the end of maintenance will be set when the number of events for PFS (287) has been reached. - Percentage of patients who were in PR at the end of induction treatment and who were in CR at the end of maintenance treatment will be set when the final analysis for PFS will be done - Safety of lenalidomide in maintenance is from randomization of the first patient to 5 years after the randomization of the last patient. Will be set when the last patient into the study will finish follow up | — |
Countries
Australia, Austria, Belgium, France, Israel, Poland, Portugal, Spain, Switzerland
Contacts
Public ContactCoordinating Investigator
Marc ANDRE
Outcome results
None listed