Inclusion Criteria:

          -  Patients must have a pathologically confirmed diagnosis of DLBCL (including DLBCL not
             otherwise specified [NOS], DLBCL germinal center B-cell [GCB] type, DLBCL activated B
             cell [ABC]/non-GCB type, T cell/histiocyte-rich large B cell lymphoma, high-grade B
             cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, and high-grade B cell
             lymphoma NOS). NOTE: DLBCL transformed from low-grade lymphoma among treatment-naive
             patients or patients previously treated with a non-anthracycline containing regimen
             are permitted

          -  Patients may have completed the first cycle of R-CHOP (off study not combined with
             TAK-659) =< 21 days prior to the first dose of TAK-659 or plan to receive the first
             cycle of R-CHOP after registration

          -  Patients must have at least one high-risk feature, including:

               -  ABC/non-GCB subtype determined by gene expression profiling or Hans algorithm by
                  immunohistochemistry per treating institution standards

               -  High-intermediate or high-risk group by National Comprehensive Cancer Network -
                  International Prognostic Index (NCCN-IPI) with score >= 4, at time of diagnosis

               -  MYC gene rearrangement (by [fluorescent in situ hybridization] FISH)

               -  MYC overexpression by immunohistochemistry (IHC) (>= 40%) and BLC2 overexpression
                  by IHC (>= 50%) or

               -  Previously treated transformed low-grade lymphoma to large B cell lymphoma with
                  prior treatment not including an anthracycline

               -  NOTE: BCL2 and/or BCL6 aberrancy are not required for enrollment, but assessment
                  for rearrangement by FISH and overexpression by IHC are required if there is
                  presence of MYC rearranged by FISH

          -  Patients must have measurable disease (defined as >= 1.5 cm in diameter) with
             correlated fluorodeoxyglucose (FDG)-avidity on positron emission tomography (PET) scan
             with Deauville score of 4 or 5 at time of diagnosis

          -  Patients must have recovered (i.e., =< grade 1 toxicity) from the reversible effects
             of prior anticancer therapy, if applicable

          -  Life expectancy of greater than 3 months

          -  Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status
             of 0-2

          -  Absolute neutrophil count >= 1000/mcL (within 14 days prior to registration)

          -  Platelets >= 75,000/mcl (NOTE: Patients with bone marrow involvement may be eligible
             with platelets >= 50,000) (within 14 days prior to registration)

          -  Hemoglobin >= 8 g/dL (within 14 days prior to registration)

               -  NOTE: Red blood cell (RBC) and platelet transfusion allowed >= 14 days prior to
                  registration

          -  Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 14 days
             prior to registration)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =<
             2.5 x institutional ULN (within 14 days prior to registration)

          -  Creatinine clearance >= 60 mL/min either as estimated by the Cockcroft-Gault equation
             or based on urine collection (12 or 24 hours) (within 14 days prior to registration)

          -  Lipase =< 1.5 x ULN with no clinical symptoms suggestive of pancreatitis or
             cholecystitis (within 14 days prior to registration)

          -  Amylase =< 1.5 x ULN with no clinical symptoms suggestive of pancreatitis or
             cholecystitis (within 14 days prior to registration)

          -  Patients must have blood pressure =< grade 1

               -  NOTE: Hypertensive patients are permitted if their blood pressure is controlled
                  to =< grade 1 by hypertensive medications

          -  Female patients must meet at least one of the following criteria:

               -  Are postmenopausal with last menstrual period at least 1 year before registration
                  OR

               -  Are surgically sterile, OR

               -  If they are of childbearing potential

                    -  Agree to practice 1 highly effective method of contraception and one
                       additional effective (barrier) method at the same time, from the time of
                       signing the informed consent through 180 days after the last dose of study
                       drug, or

                    -  Agree to practice true abstinence, when is in line with the preferred and
                       usual lifestyle of the subject. Periodic abstinence (e.g., calendar,
                       ovulation, symptothermal, postovulation methods), withdrawal, spermicides
                       only, and lactational amenorrhea are not acceptable methods of
                       contraception. Female and male condoms should not be used together

                    -  Agree not to donate eggs (ova) during the course of this study or 180 days
                       after receiving their last dose of study drug

          -  Male patients, even if surgically sterilized (i.e., status post-vasectomy), must:

               -  Agree to practice effective barrier contraception during the entire study
                  treatment period and through 180 days after the last dose of study drug, or

               -  Agree to practice true abstinence, when this is in line with the preferred and
                  usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation,
                  symptothermal, postovulation methods for the female partner] and withdrawal are
                  not acceptable methods of contraception. Female and male condoms should not be
                  used together.)

               -  Agree not to donate sperm during the course of this study or within 180 days
                  after receiving their last dose of study drug

          -  Female of childbearing potential (FOCBP) must have a negative pregnancy test =< 7 days
             prior to registration on study

          -  Voluntary written consent must be given before performance of any study related
             procedure not part of standard medical care, with the understanding that consent may
             be withdrawn by the patient at any time without prejudice to future medical care

          -  Patients must have the ability to swallow oral medication

          -  Patients must be willing and able to complete study-required procedures

        Exclusion Criteria:

          -  Patients with exposure to chemotherapy or immunotherapy =< 30 days prior to starting
             study treatment are not eligible

               -  NOTE: Patients may receive at most 1 cycle of R-CHOP, rituximab, or systemic
                  corticosteroids within this timeframe

               -  NOTE: If patient is registered prior to completion of washout, start date of
                  treatment will need to be confirmed prior to registration

          -  Patients with prior exposure to a SYK inhibitor are not eligible

               -  NOTE: Examples of SYK inhibitors include fostamatinib (R788), entospletinib
                  (GS-9973), cerdulatinib (PRT062070), and TAK-659

          -  Patients with untreated brain metastases or leptomeningeal metastases are not eligible

          -  Patients with known hypersensitivity (e.g. anaphylactic and anaphylactoid reactions)
             to TAK-659 or components of R-CHOP are not eligible

          -  Patients with history of drug-induced pneumonitis requiring treatment with steroids;
             history of idiopathic pulmonary fibrosis, organizing pneumonia, or evidence of active
             pneumonitis on screening imaging are not eligible

               -  NOTE: A history of radiation pneumonitis in the radiation field (fibrosis) is
                  permitted

          -  Patients with known hepatitis B surface antigen positive, or known or suspected active
             hepatitis C infection are not eligible

          -  Patients who are known to be human immunodeficiency virus (HIV) positive are not
             eligible

          -  Patients must not have had autologous stem cell transplant within 6 months prior to
             registration

          -  Patients must have not had allogeneic stem cell transplant at any time

          -  Patients who have received systemic anticancer treatment (including investigational
             agents) or radiotherapy less than 3 weeks before the first dose of study treatment (=<
             5 times half-life for large molecule agents or =< 4 weeks with evidence of disease
             progression if 5 times half-life is > 4 weeks) are not eligible

               -  NOTE: Patients may receive R-CHOP cycle 1

               -  NOTE: If patient is registered prior to completion of washout, start date of
                  treatment will need to be confirmed prior to registration

          -  Use or consumption of the following substances is not permitted:

               -  Medications or supplements that are known to be inhibitors of P-gp and/or strong
                  reversible inhibitors of CYP3A within 5 times the inhibitor half-life (if a
                  reasonable half-life estimate is known), or within 7 days (if a reasonable
                  half-life estimate is unknown), before the first dose of study drug. The use of
                  these agents is not permitted during the study

               -  Medications or supplements that are known to be strong CYP3A mechanism-based
                  inhibitors or strong CYP3A inducers and/or P-gp inducers within 7 days, or within
                  5 times the inhibitor or inducer half-life (whichever is longer), before the
                  first dose of study drug. The use of these agents is not permitted during the
                  study

               -  Grapefruit-containing food or beverages within 5 days before the first dose of
                  study drug. Note that grapefruit-containing food and beverages are prohibited
                  during the study

          -  Patients who have major surgery, per principal investigator (PI) discretion, =< 14
             days before the first dose of study drug and those who have not recovered fully from
             any complications from surgery are not eligible

          -  Patients who have systemic infection requiring parenteral antibiotic therapy or other
             serious infection (bacterial, fungal or viral) =< 21 days before the first dose of
             study drug are not eligible

               -  NOTE: Patients who are at substantial risk of developing an infection may receive
                  prophylaxis at the start of study treatment per investigator?s discretion

          -  Patients with an active secondary malignancy that requires treatment are not eligible

               -  NOTE: Patients with non-melanoma skin cancer or carcinoma in situ of any type are
                  not excluded if they have undergone complete resection and are considered
                  disease-free at the time of registration

          -  Patients with known gastrointestinal (GI) disease or GI procedure that could interfere
             with the oral absorption or tolerance of TAK-659 are not eligible (this may include
             difficulty swallowing tablets or diarrhea > grade 1 despite supportive therapy)

          -  Patients who received treatment with high-dose corticosteroids for anticancer purposes
             =< 7 days before the first dose of TAK-659 are not eligible

               -  NOTE: Prednisone and other steroids given as part of the R-CHOP regimen and as
                  pre-medications are exceptions throughout the study. Patients may also receive
                  steroids prior to starting chemotherapy to improve performance status. In other
                  contexts, daily dose equivalent to 10 mg oral prednisone or less is permitted.
                  Corticosteroids for topical use or in nasal spray or inhalers are allowed

          -  Patients who have known central nervous system (CNS) lymphomatous involvement are not
             eligible

          -  Patients who have an uncontrolled intercurrent illness, in the opinion of the
             investigator, including, but not limited to any of the following, are not eligible:

               -  Uncontrolled pulmonary disease

               -  Active CNS disease that would interfere with study participation

               -  Active infection requiring parenteral systemic treatment

               -  Psychiatric illness/social situations that would limit compliance with study
                  requirements

               -  Any other illness or condition that the treating investigator feels would
                  interfere with study compliance or would compromise the patient?s safety or study
                  endpoints

          -  Patients with any of the following cardiovascular conditions are excluded:

               -  Acute myocardial infarction within 6 months before starting study drug

               -  Current or history of New York Heart Association class III or IV heart failure

               -  Evidence of current, uncontrolled cardiovascular conditions including cardiac
                  arrhythmias, angina, pulmonary hypertension, or electrocardiographic evidence of
                  acute ischemia or active conduction system abnormalities

               -  Fridericia corrected QT interval (QTcF) > 450 milliseconds (msec) (men) or > 475
                  msec (women) on a 12-lead electrocardiography (ECG) during the screening period

               -  Abnormalities on 12-lead ECG including, but not limited to, changes in rhythm and
                  intervals that, in the opinion of the investigator, are considered to be
                  clinically significant

               -  Abnormal left ventricular function (ejection fraction [EF] < 50%, as indicated by
                  baseline echocardiography [ECHO])

          -  Female patients who are both lactating and breastfeeding or have a positive serum
             pregnancy test during the screening period or a positive urine pregnancy test on day 1
             before first dose of TAK-659