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

Study Overview
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Brief Summary
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This study is evaluating the efficacy of acalabrutinib in combination with rituximab (Arm 1) versus ibrutinib (Arm 2) versus acalabrutinib (Arm 3) for the treatment of relapsed or refractory (R/R) mantle cell lymphoma (MCL).

Official Title
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A Randomized, Multicenter, Open Label, Phase 3 Study of Acalabrutinib (ACP-196) in Combination With Rituximab Versus Ibrutinib Versus Acalabrutinib Alone in Subjects With Relapsed or Refractory (R/R) Mantle Cell Lymphoma (MCL)

Conditions
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Mantle Cell Lymphoma

Intervention / Treatment
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* Drug: acalabrutinib
* Drug: ibrutinib
* Drug: rituximab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: acalabrutinib plus rituximab<br>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). | Drug: acalabrutinib<br> <br> Drug: rituximab<br> <br> |
| Active Comparator: ibrutinib<br>Ibrutinib will be orally administered until disease progression or unacceptable toxicity (approximately 200 subjects). | Drug: ibrutinib<br> <br> |
| Experimental: acalabrutinib<br>Acalabrutinib will be orally administered until disease progression or unacceptable toxicity (approximately 50 subjects). | Drug: acalabrutinib<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Btk, Bruton tyrosine kinase inhibitor, ACP-196, Mantle Cell Lymphoma, MCL