Histologically proven CD20+ diffuse large B cell lymphoma (WHO Classification), in patients aged =80 years and not previously treated. 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
Product Name: Rituximab SC
Product Code: RO 45-2294
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Concentration unit: mg milligram(s)
Conc
Sponsors
LYSARC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patient with histologically proven CD20+ diffuse large B-cell lymphoma (DLBCL) (WHO classification 2008) including all clinical subtypes (primary mediastinal, intravascular, etc…), with all aaIPI. May also be included: - De Novo transformed DLBCL from low grade lymphoma (Follicular, other...) and DLBCL associated with some small cell Infiltration in bone marrow or lymph node - 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+ Aggressive B-cell lymphoma unclassifiable • With a CD10 immunostaining performed by the participating center pathologist • Aged = 80 years old • Ann Arbor stage II, III or IV • Patient previously untreated for DLBCL • ECOG performance status = 2 • With a minimum life expectancy of 3 months • Negative HIV, HBV and HCV serologies test within 4 weeks before inclusion (except after hepatitis B vaccination or for patients who are HBs Ag negative, anti-HBs positive and/or anti-HBc positive but viral DNA negative) • Patient able to give his consent and having signed a written Informed consent • Patient affiliated to social security system, if applicable • Male patients must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for 3 months following study drug discontinuation, even if they have undergone a successful vasectomy • All patients must agree to fulfill the global Lenalidomide Pregnancy Prevention Risk Management Plan as applicable according to the randomization arm (experimental arm) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 250
Exclusion criteria
Exclusion criteria: • Any other histological type of lymphoma, Burkitt included • Any history of treated or non-treated small-B cell lymphoma • Central nervous system or meningeal involvement by lymphoma • Contra-indication to any drug contained in the chemotherapy regimens ; for anthracycline use, ejection fraction should be > 50% • Any serious active disease (according to the investigator’s decision) • History of deep venous thrombosis or arterial thromboembolism events within the past 12 months before inclusion • Poor renal function (creatinine clearance 30 µmol/l, transaminases >2.5 maximum normal level) unless these abnormalities are related to the lymphoma • Poor bone marrow reserve as defined by neutrophils <1.5 G/l or platelets <100 G/l, unless related to bone marrow infiltration • Any history of cancer during the last 5 years with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma. 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 (i.e., 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 • Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy and during the study • Prior treatment with anti-CD20 monoclonal antibody or alemtuzumab within 3 months prior to start of therapy • Prior use of lenalidomide • Prior = Grade 3 allergic reaction/hypersensitivity to thalidomide • Prior = Grade 3 rash or any desquamating (blistering) rash while taking thalidomide • Subjects with = Grade 2 neuropathy • Adult patient under tutelage • Female of childbearing potential are excluded. (Note: Females are defined as not of childbearing potential if there is documentation of “natural menopause for at least 24 consecutive months, a hysterectomy or bilateral oophorectomy”)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective of the study is to compare the efficacy of R2-miniCHOP and R-miniCHOP in patients = 80 years with not previously treated CD20+ diffuse large B-cell lymphoma as measured by the overall survival (OS) ;Primary end point(s): The primary endpoint is the overall survival (OS). ;Timepoint(s) of evaluation of this end point: Overall survival will be measured from the date of randomization to the date of death from any cause. Alive patients will be censored at their last contact. ;Secondary Objective: Secondary objectives are : - To evaluate the efficacy and the safety of R2-miniCHOP as measured by the PFS (Progression Free Survival), EFS (Event Free Survival), the DoR (duration of response), the DFS (disease free survival), response rate at the end of the treatment, the additional toxicities - To evaluate the simplified scale prognostic impact (IADL, MNA, G8, CIRS-G) - To assess the quality of life before and after treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Progression-Free Survival (PFS) - Event-Free Survival (EFS) - Duration of Response (DoR) - Disease-Free Survival (DFS) - Overall Survival (OS) according to GCB/non-GCB phenotype - Response Rate at the end of the treatment (after end of the 6th cycle of treatment or at premature withdrawal) will be assessed using disease response evaluation at end of treatment, according to Cheson 1999 - Simplified geriatric scale, based on four geriatric tools that will be performed before any chemotherapy administration (IADL, MNA, G8, and CIRS-G scales) will be analyzed in order to have a picture of the population at baseline, to evaluate the prognosis impact in OS and PFS of each scale and to evaluate the toxicity predictive power of these scales - Health related Quality of Life (HRQoL) will be assessed by the QLQ-C30 and the QLQ-ELD14 at randomization and at end of treatment. The improvement or not of the QoL will therefore be assessed;Timepoint(s) of evaluation of this end point: PFS : time from randomization to the first observation of documented disease progression/relapse or death due to any cause. EFS : measured from the date of randomization to the date of first documented disease progression/relapse (Cheson 1999), initiation of new anti-lymphoma therapy or death from any cause. DoR : measured from the time of attainment of CR/CRu or PR to the date of first documented disease progression/relapse or death from any cause. DFS : measured from the date of attainment of CR/CRu (at the end of treatment or at withdrawal evaluation) to the date of first observation of documented disease progression or death due to any cause. Four geriatric tools : before any chemotherapy administration. HRQoL assessed at randomization and at end of treatment. | — |
Countries
Belgium, France, Portugal
Contacts
Public ContactFabienne MORAND
LYSARC
Outcome results
None listed