Efficacy of Lenalidomide in Combination With Subcutaneous Rituximab + miniCHOP in DLBCL Patients of 80 y/o or+
Efficacy of Lenalidomide in Combination With Subcutaneous Rituximab + miniCHOP in DLBCL Patients of 80 y/o or+
The purpose of this study is to compare the efficacy of R2-miniCHOP (Sub-cutaneous
 Rituximab-miniCHOP + lenalidomide) and R-miniCHOP (Sub-cutaneous Rituximab-miniCHOP) in
 patients aged 80 years old or more with not previously treated cluster of differentiation
 antigen 20 positive (CD20+) diffuse large B-cell lymphoma as measured by the overall survival
 (OS).The SENIOR trial will evaluate the tolerance and efficacy of the combination of the
 R2-miniCHOP regimen and compare this experimental arm to the standard R-miniCHOP regimen.The
 statistical plan is based on the hypothesis of an increase by 15% of the 2y-OS in favor of
 the experimental arm, as compared to the reference arm (R-miniCHOP).
The purpose of this study is to compare the efficacy of R2-miniCHOP (Sub-cutaneous
 Rituximab-miniCHOP + lenalidomide) and R-miniCHOP (Sub-cutaneous Rituximab-miniCHOP) in
 patients aged 80 years old or more with not previously treated cluster of differentiation
 antigen 20 positive (CD20+) diffuse large B-cell lymphoma as measured by the overall survival
 (OS).

 Primary endpoint of the study is to compare the efficacy of R2-miniCHOP (Sub-cutaneous
 Rituximab-miniCHOP + lenalidomide) and R-miniCHOP ((Sub-cutaneous Rituximab-miniCHOP) in
 patients of 80 years old or more with not previously treated CD20+ diffuse large B-cell
 lymphoma as measured by the overall survival (OS).

 Secondary endpoints 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 This study is a multicentric,
 phase III, open-label, randomized (1:1) trial evaluating the efficacy of R2-miniCHOP in
 patients aged of 80 years or more with non-previously treated CD20+ diffuse large B-cell
 lymphoma (age-adjusted IPI= 0 to 3), Ann Arbor stage II to IV with a performance status
 ECOG from 0 to 2.

 This study includes a run in phase to assess feasibility, safety and tolerance of
 subcutaneous rituximab injections and oral lenalidomide (10 mg D1-D14) in combination with
 dose-reduced intensity CHOP regimen.
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 age-adjusted International Prognostic Index (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 (according to WHO classification); or CD20+ Aggressive B-cell
 lymphoma unclassifiable.

 -  With a Cluster of Differentiation antigen 10 (CD10) immunostaining performed by the
 participating center pathologist

 -  Aged ≥ 80 years old

 -  Ann Arbor stage II, III or IV

 -  Patient previously untreated for DLBCL Lymphoma

 -  Eastern Cooperative Oncology Group (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 (randomization arm)

 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 < 40 ml/min, according to Modification of
 Diet in Renal Disease (MDRD) formula)

 -  Poor hepatic function (total bilirubin level >30mmol/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")