A Study of Acalabrutinib in Combination With Rituximab Versus Ibrutinib Versus Acalabrutinib in Subjects With Relapsed or Refractory Mantle Cell Lymphoma

Recruitment & Eligibility

Inclusion Criteria

Men and women ≥ 18 years of age.
Pathologically confirmed mantle cell lymphoma (MCL).
Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
Agreement to use highly effective forms of contraception during the study and for 90 days after the last dose of acalabrutinib or ibrutinib or 12 months after the last dose of rituximab (whichever is longest).
Disease that has relapsed, or been refractory to, ≥ 1 prior treatment regimen for mantle cell lymphoma (MCL).
Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty.
Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local patient privacy regulations).

Exclusion Criteria

Any history of central nervous system (CNS) lymphoma or leptomeningeal disease.
Prior exposure to ibrutinib or to a B-cell receptor (BCR) inhibitor.
Significant cardiovascular disease.
Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, 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.
Known history of infection with human immunodeficiency virus (HIV).
History of hepatitis B (HBV) infection or active infection with hepatitis C (HCV).
Breastfeeding or pregnant.

Study & Design

Arm && Interventions

Group	Intervention	Description
ibrutinib	ibrutinib	Ibrutinib will be orally administered until disease progression or unacceptable toxicity (approximately 200 subjects).
acalabrutinib	acalabrutinib	Acalabrutinib will be orally administered until disease progression or unacceptable toxicity (approximately 50 subjects).
acalabrutinib plus rituximab	acalabrutinib	Acalabrutinib will be orally administered until disease progression or unacceptable toxicity. Rituximab IV infusions will be administered weekly for 4 weeks and on Day 1 of Cycle 3 through 8, and thereafter every other cycle for less than or equal to two years (approximately 200 subjects).
acalabrutinib plus rituximab	rituximab	Acalabrutinib will be orally administered until disease progression or unacceptable toxicity. Rituximab IV infusions will be administered weekly for 4 weeks and on Day 1 of Cycle 3 through 8, and thereafter every other cycle for less than or equal to two years (approximately 200 subjects).

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS) assessed by Independent Review Committee (IRC) per the Lugano Classification for Non-Hodgkin Lymphoma (NHL). The primary analysis is a comparison of progression-free survival (PFS) between Arm 1 and Arm 2.	48 months

Secondary Outcome Measures

Name	Time	Method
Investigator-assessed progression-free survival (PFS) per the Lugano Classification for Non-Hodgkin Lymphoma (NHL).	48 months
Investigator-assessed overall response rate (ORR) per the Lugano Classification for Non-Hodgkin Lymphoma (NHL).	48 months
Overall survival (OS).	48 months
IRC-assessed duration of response (DOR) per the Lugano Classification for Non-Hodgkin Lymphoma (NHL).	48 months

Recruitment & Eligibility