Inclusion Criteria:

          -  Participants must have histologically confirmed diffuse large B-cell lymphoma (DLBCL).
             Participants with previously diagnosed indolent lymphoma (follicular and marginal zone
             lymphoma but not small lymphocytic lymphoma) who have transformed to DLBCL are
             eligible only if they have not previously been treated for indolent lymphoma.

             --If participants received single rituximab (maximum 4-8 doses with no maintenance)
             for their low grade lymphoma ≥12 months prior to starting study drug are eligible to
             participate

          -  Participants must have radiographically measurable disease. At least one
             bi-dimensionally measurable nodal lesion ≥1.5 cm in its longest diameter by CT scan or
             MRI, as defined by the Lugano Classification

          -  Patients participating in the phase II part are allowed to receive brief (<15 days)
             treatment with glucocorticoids (max dose of prednisone 40 mg) and/or 1 cycle of
             chemotherapy such as R-CHOP [or some component(s) thereof] for the diagnosis of B-cell
             lymphoma provided they had all necessary staging tests performed prior to R-CHOPor
             steroids including CT and/or PET/CTscans, and bone marrow biopsy. Treatment must occur
             within 30 days prior to enrollment.

          -  No prior therapy with PI3K inhibitors or Bruton tyrosine kinase (BTK) inhibitors

          -  ECOG Performance status ≤2. Performance Status of 3 will be accepted if impairment is
             caused by DLBCL complications and improvement is expected once therapy is initiated.

          -  Participants must have adequate hematologic, hepatic, and renal function as defined
             below:

               -  Hemoglobin ≥9.0g/dl unless the anemia is clearly due to DLBCL. If there is BM
                  involvement, this criteria can be waived after discussion with the Sponsor
                  Investigator (per investigators discretion).

               -  Absolute neutrophil count≥1,000/mcL, unless the neutropenia is clearly due to
                  DLBCL. If there is BM involvement, this criteria can be waived after discussion
                  with the Sponsor Investigator(per investigator discretion)

               -  Platelet count ≥75,000/mcl unless thrombocytopenia is clearly due to DLBCL. If
                  there is BM involvement, this criteria can be waived after discussion with the
                  Sponsor Investigator(per investigator discretion)

               -  Bilirubin ≤ 2.0 x ULN unless considered secondary to Gilbert's syndrome, in which
                  case ≤ 3 x ULN

               -  AST (SGOT) < 2.0 x institutional upper limit of normal

               -  ALT (SGPT) < 2.0 x institutional upper limit of normal

               -  Creatinine clearance ≥45 mL/min calculated by Cockcroft-Gault or 24 hour
                  collection

          -  Adequate cardiac function left ventricular ejection fraction (LVEF) ≥50% as assessed
             by echocardiogram or MUGA (Multi Gated Acquisition Scan).

          -  QT-interval corrected according to Fridericia's formula (QTcF) ≤450 milliseconds (ms);
             participants with QTc < 480 msec may be enrolled provided the QTc prolongation is due
             to a right bundle branch block and stable .

          -  Negative pregnancy test in women of child-bearing age. The effects of ME-401 on the
             developing human fetus are unknown. For this reason and because chemotherapeutic
             agents used in this study are known to be teratogenic, women of child-bearing
             potential and men must agree to use adequate contraception (double barrier method of
             birth control or abstinence) 2 weeks prior to initiation of treatment, for the
             duration of study participation and for 3 months after completing treatment. Should a
             woman become pregnant or suspect that she is pregnant while she or her partner is
             participating in this study, she should inform the treating physician immediately. Men
             must agree to refrain from sperm donation for at least 90 days after the last dose of
             ME-401

          -  Participants must have the ability to understand and the willingness to sign a written
             informed consent document.

          -  International Prognostic Index must be documented:

               -  ECOG performance status ≥2

               -  Age ≥60 years

               -  extranodal sites ≥ 2

               -  LDH >upper limit of normal

               -  Ann Arbor Stage III or IV

               -  Is there evidence of transformation from indolent lymphoma?

        Exclusion Criteria:

          -  Participants receiving any other investigational agents.

          -  Known CNS involvement by lymphoma. Participants at high risk for secondary CNS
             involvement but without neurologic symptoms suspected to be due to lymphoma are
             allowed to be enrolled and receive prophylactic intrathecal chemotherapy including but
             not limited to methotrexate, cytarabine and glucocorticoids. Participants who are
             enrolled and subsequently identified to have pathologic confirmation of CNS
             involvement by lymphoma may be continued on study at the discretion of the principal
             investigator.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to R-CHOP.

          -  Participants with ongoing uncontrolled illness including, but not limited to ongoing
             significantly active infections requiring intravenous antibiotics, hypertension,
             angina, arrhythmias, pulmonary disease, or autoimmune dysfunction.

          -  Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia.

          -  Ongoing drug-induced pneumonitis.

          -  History of clinically significant gastrointestinal (GI) conditions, particularly:

               -  Known GI condition that would interfere with swallowing or the oral absorption or
                  tolerance of study drug

               -  Pre-existing malabsorption syndrome or other clinical situation that would

          -  Active congestive heart failure (New York Heart Association [NYHA] Class>2),
             symptomatic ischemia, or conduction abnormalities uncontrolled by conventional
             intervention or myocardial infarction within six months prior to enrollment.

          -  Participants who have tested positive for hepatitis B surface antigen and/or hepatitis
             B core antibody PLUS have detectable viral load on hepatitis B polymerase chain
             reaction (PCR) assay (participants with a negative PCR assay are permitted with
             appropriate anti-viral prophylaxis)

          -  Positive hepatitis C virus antibody (HCV Ab) participants with positive hepatitis C
             antibody are eligible if they are negative for hepatitis C virus by PCR

          -  HIV-positive participants on combination antiretroviral therapy are ineligible because
             of the potential for pharmacokinetic interactions with ME-401

          -  Pregnant or breastfeeding women are excluded from this study because there are no
             studies assessing the reproductive and developmental toxicity or excretion into breast
             milk of ME-401. Because there is an unknown, but potential risk for adverse events in
             nursing infants secondary to treatment of the mother with ME-401, breastfeeding should
             be discontinued if the mother is treated with ME-401. These potential risks may also
             apply to other drugs used in this study.

          -  Other malignancies within the past 3 years except for adequately treated carcinoma of
             the cervix or basal or squamous cell carcinomas of the skin, or low-risk prostate
             cancer after curative therapy.

          -  Participants who have had major surgical procedures or significant traumatic injury
             within 28 days prior to study treatment.

          -  Psychiatric illness/social situations that would interfere with study compliance