Inclusion Criteria:

          1. Patients with histologically confirmed de novo DLBCL (CD20 positive) (cf section 20.6
             - Appendix 4)

          2. Age between 60 and 80 years included, on the day of the informed consent document
             signature

          3. Age adjusted International Prognosis Index (aaIPI) score ≥ 1

          4. No prior treatment for DLBCL. However prephase treatment with 1mg/kg/day prednisone or
             equivalent, for a maximum of 14 days, is permitted prior to begin the treatment

          5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (0 or 1 only
             for phase 1b)

          6. Life expectancy of ≥ 90 days (3 months) before starting Entospletinib

          7. Signed informed consent

          8. At least one bi-dimensionally measurable lesion defined as at least one node or tumor
             lesion on CT scan ≥ 1.5 cm

          9. fluorodeoxyglucose (FDG) positron emission tomography (PET-CT) performed at baseline
             with a FDG positive result

         10. Adequate hematologic functions defined as follows (unless secondary to bone marrow
             involvement by lymphoma):

               -  Absolute neutrophil count (ANC) > 1.5 X 10^9 G/l and

               -  Platelets count ≥ 75 X 10^9/l without platelet transfusion dependency during the
                  last 7 days and

               -  Haemoglobin level > 9 g/dl (may receive transfusion)

         11. Adequate liver function defined as follows:

               -  Total bilirubin <1.5 upper limit of normal (ULN) except for unconjugated
                  hyperbilirubinemia of Gilbert's syndrome and

               -  Alkaline phosphatase (in absence of bone disease), alanine aminotransferase (ALT)
                  and aspartate aminotransferase (AST) < 3 X ULN

         12. Adequate renal function as calculated by a creatinine clearance > 40 ml/min by local
             institutional formula

         13. Patients with prior Hepatitis B must be given antiviral prophylaxis and hepatitis B
             virus (HBV) DNA monitored; Patients with prior Hepatitis C are eligible if, hepatitis
             C virus (HCV) RNA is undetectable.

         14. Left ventricular ejection fraction (LVEF) ≥ 50% of echocardiography or multiple gated
             acquisition (MUGA) scan

         15. Adequate tissue for central retrospective testing for cell of origin (10-15 slides of
             tumor biopsy must be available at baseline)

         16. Heterosexually active females of childbearing potential (as defined in the protocol)
             must:

               -  have a negative serum pregnancy test at baseline and prior to the first study
                  drug administration (C1D-4)

               -  have practiced at least 1 reliable method of contraception for at least 2 months
                  prior to the first study drug administration (C1D-4)

               -  agree to utilize highly effective methods of contraception (as defined in the
                  protocol) from Cycle 1 Day -4 until 12 months following the last treatment
                  administration

         17. Heterosexually active males with partners of childbearing potential must agree to use
             reliable forms of contraception during treatment and up to 12 months after last
             treatment administration

         18. Male subjects must agree to avoid sperm donation from Cycle 1 Day -4 until 12 months
             following the last treatment administration

        Exclusion Criteria:

          1. Central nervous system or meningeal involvement with DLBCL

          2. Contraindication to any drug contained in the chemotherapy regimen

          3. Prior treatment with Entospletinib or other spleen tyrosine kinase (SYK ) inhibitor

          4. Patients with a prior history of other malignancy, exceptions include:

               -  a subject who has been disease-free after curative local treatment (surgical
                  resection) for at least 3 years,

               -  a subject with a history of a completely resected non-melanoma skin cancer or in
                  situ carcinoma with surgical complete excision.

          5. Patients taking current therapy with proton pump inhibitors and current therapy with
             medicines that are strong Cytochrome P450 3A (CYP3A) or CYP2C9 inducers, or moderate
             CYP2C9 inducers.

          6. Ongoing active pneumonitis

          7. Peripheral sensory or motor neuropathy grade > 1.

          8. Major surgery within 4 weeks before first dose of study drug (minor procedures
             including transcutaneous biopsy, central line placement are permitted at any time)

          9. Inability to take oral medication or malabsorption syndrome or any other uncontrolled
             gastrointestinal condition that would impair ability to take entospletinib

         10. Significant cardiovascular impairment: congestive heart failure greater than New York
             Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke
             within 6 months of first dose of entospletinib or ventricular arrhythmia

         11. Active infection as judged by the investigator

         12. Known hypersensitivity to ENTO

         13. Congenital immunodeficiency or known HIV (human immunodeficiency virus infection) or
             active viral hepatitis B or C

         14. Any other major illness that in the investigator's judgement, will substantially
             increase the risk associated with the subject's participation in the study

         15. Subjects who have undergone a solid organ transplant and stem cell transplant

         16. Previous treatment for B cell lymphoma or Richter's transformation

         17. Primary Mediastinal B Cell Lymphoma