Study of Acalabrutinib and Rituximab in Untreated Elderly and/or Frail Patients With DLBCL

Inclusion Criteria:

• ≥ 80 years of age at the time of screening, or

• ≥ 65 to 79 years of age at the time of screening and considered ineligible forchemoimmunotherapy

• Histologically documented DLBCL

• No prior treatment for DLBCL

• Stage II, III, or IV disease by the Ann Arbor Classification .

• Eastern Cooperative Oncology Group performance status of 0, 1, or 2 with nodeterioration over the previous 2 weeks prior to baseline or day of the first dosingexcept when due to underlying lymphoma.

• At least 1 lesion that can be accurately measured at baseline as ≥ 10 mm in thelongest diameter with computed tomography or magnetic resonance imaging and issuitable for accurate repeated measurements.

• Adequate organ and marrow function independent of growth factor or transfusionsupport within 1 week of Screening.

Exclusion Criteria:

• Any evidence of diseases (such as severe or uncontrolled systemic diseases,including uncontrolled hypertension, renal transplant, and active bleedingdiseases), that would make the study undesirable for the patient or that wouldimpact compliance with the protocol.

• History of prior or current malignancy, that would affect compliance with theprotocol or interpretation of the results.

• Serologic status reflecting active hepatitis B or C infection.

• Serological positivity or known infection with HIV.

• Active central nervous system involvement by lymphoma, leptomeningeal disease, orspinal cord compression.

• Any comorbidity or organ system impairment rated with a single Cumulative IllnessRating Scale-Geriatric score (CIRS-G) of 4 or a total CIRS-G score of > 17.

• History of or ongoing confirmed Progressive Multifocal Leukoencephalopathy.

• Known active significant infection.

• History of stroke or intracranial haemorrhage within 6 months before the first doseof study drug.

• History of bleeding diathesis (eg, haemophilia, von Willebrand disease).

• Major surgical procedure within 30 days of first dose of study intervention oranticipated major surgery during the study timeframe.

• Requires or receiving anticoagulation with warfarin or equivalent vitamin Kantagonists.

• Received a live virus vaccination within 28 days of the first dose of study drug.