non-germinal center diffuse large B-cell lymphoma

Phase 3 randomized, double-blind, placebo-controlled, study to evaluate the efficacy and safety of acalabrutinib plus rituximab,cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as compared with placebo plus R-CHOP in subjects ≤65 years of age with previously untreated non-germinal center diffuse large B-cell lymphoma (activated B-cell (ABC) and unclassified).

ACP-196

Acalabrutinib

capsule

100

Primary Outcome Measures :
Progression-free survival (PFS) per the Lugano Classification for NHL in Arm A compared to Arm B [ Time Frame: 60 months ]

Secondary Outcome Measures :
Investigator-assessed event-free survival (EFS) for NHL in Arm A compared to Arm B [ Time Frame: 60 months ]
Overall survival in Arm A compared to Arm B [ Time Frame: 60 months ]
Percentage of Participants Who Achieved a Complete Response (CR) per 2014 Lugano Classification at the end of study treatment [ Time Frame: Up to 32 weeks ]

Inclusion Criteria:

Men and women, age ≥18 and ≤65 years
Pathologically confirmed DLBCL, sufficient diagnostic material should be available to forward to a central laboratory for gene expression profiling and pathology review.
No prior treatment for DLBCL
Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
International Prognostic Index (IPI) score of 2 to 5
Disease Stage II to IV by the Ann Arbor Classification
Adequate organ and marrow function
Agreement to use highly effective forms of contraception during the study and 12 months after the last dose of rituximab

Exclusion Criteria:

Evidence of severe or uncontrolled systemic diseases
Known history of a bleeding diathesis (i.e., haemophilia, von Willebrand disease)
History of stroke or intracranial haemorrhage in preceding 6 months.
Known CNS lymphoma or leptomeningeal disease
Known primary mediastinal lymphoma
Known High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements
Prior history of indolent lymphoma
History of or ongoing confirmed progressive multifocal leukoencephalopathy
Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of first dose of study drug, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
Uncontrolled active systemic fungal, bacterial, viral, or other infection
Prior anthracycline use ≥150 mg/m2
Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer.
Requires treatment with proton pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Patients receiving proton pump inhibitors who switch to short-acting H2-receptor antagonists or antacids are eligible for enrolment into this study.