Inclusion Criteria:

          -  Signed and dated informed consent document indicating that the participant (or legally
             acceptable representative) has been informed of all pertinent aspects of the trial

          -  All patients age ≥75 years and participants aged 70-74 years who are determined to be
             unfit or frail by Cumulative Illness Rating Score-Geriatrics (CIRS-G) scale

               -  For participants aged 70-74 years: CIRS-G score with 5-8 comorbid conditions
                  scored 2 or ≥1 comorbidity scored 3-4

          -  Newly diagnosed, untreated, biopsy proven CD20 positive DLBCL (including high grade
             B-cell lymphoma & T-cell/histiocytic rich large B-cell lymphoma). Participants with
             discordant bone marrow (i.e. involved by low-grade/indolent NHL) are eligible.
             Participants with transformed DLBCL from underlying low-grade disease are eligible.
             Participants with composite DLBCL and concurrent low-grade lymphoma are eligible.

               -  Copy of pathology report must be sent to coordinating site to confirm diagnosis
                  for eligibility

               -  Participants with prior treatment for low grade NHL with non-anthracycline based
                  regimens are eligible

          -  Measurable disease by PET/CT or Bone Marrow (BM) biopsy prior to enrollment

          -  Left ventricular ejection fraction ≥50% by resting echocardiography or resting
             Multi-gated acquisition (MUGA) scan

          -  Karnofsky Performance Score ≥50

          -  Ann Arbor Stage II bulky, III, or IV disease

          -  Minimum life expectancy greater than 3 months

          -  Negative HIV test

          -  For participants with hepatitis B virus antigen (HbsAg) or core antibody (HbcAb)
             seropositivity, participants must have a negative Hep B viral load and an appropriate
             prophylaxis plan must be in place during chemotherapy therapy treatment. For all
             participants that have Hep B core antibody positive, they should take entecavir
             prophylaxis (0.5 mg PO daily) until 1 year from completion of chemotherapy. Hep B
             viral load should be checked on these participants prior to starting chemotherapy and
             every 3 months thereafter if initial Hep B viral load is negative (+/- 1 week if
             chemotherapy cycle is delayed). If Hep B viral load is positive, Hepatology or
             Identification (ID) referral is recommended, and hepatitis B virus (HBV) viral load
             should be checked monthly

          -  For participants with hepatitis C Ab (HbcAb) positivity, a viral load must be checked
             and be negative for enrollment

          -  Intrathecal chemotherapy for central nervous system prophylaxis only can be given at
             the discretion of the primary oncologist

        Exclusion Criteria:

          -  History of previous anthracycline exposure

          -  Central Nervous System (CNS) or meningeal involvement at diagnosis

          -  Creatinine Clearance <25 mL/min by body surface area (BSA)-adjusted Cockroft-Gault

          -  Poor hepatic function, defined as total bilirubin concentration greater than 3.0 mg/dL
             or transaminases over 4 times the maximum normal concentration, unless these
             abnormalities are felt to be related to the lymphoma.

          -  Pulmonary dysfunction defined as >2 L of oxygen required by nasal cannula to maintain
             peripheral capillary oxygen saturation (SpO2) ≥90% unless felt to be related to
             underlying lymphoma.

          -  Myocardial Infarction within 6 months of enrollment

          -  Active, uncontrolled infectious disease

          -  Concurrent bone marrow malignancies (e.g. myelodysplastic syndrome) or poor
             bone-marrow reserve, defined as neutrophil count less than 1.5×10⁹/L or platelet count
             less than 100×10⁹/L, unless caused by bone-marrow infiltration with lymphoma

          -  History of a second concurrent active malignancy or prior malignancy which required
             chemotherapy treatment within the preceding 2 years

          -  Treatment with any investigational drug within 30 days before the planned first cycle
             of chemotherapy

          -  Unable or unwilling to sign consent