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

Sponsor

Acerta Pharma BV (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT02735876

Collaborator

(none)

Enrollment

Arms

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Mantle Cell Lymphoma	Drug: acalabrutinib Drug: ibrutinib Drug: rituximab	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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)

Study Start Date :

May 1, 2016

Anticipated Primary Completion Date :

Jun 1, 2020

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: acalabrutinib plus 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).

Drug: acalabrutinib

Drug: rituximab

Active Comparator: ibrutinib

Ibrutinib will be orally administered until disease progression or unacceptable toxicity (approximately 200 subjects).

Drug: ibrutinib

Experimental: acalabrutinib

Acalabrutinib will be orally administered until disease progression or unacceptable toxicity (approximately 50 subjects).

Drug: acalabrutinib

Outcome Measures

Primary Outcome Measures

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

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]

Other Outcome Measures

Incidence of adverse events (AEs), serious adverse events (SAEs), and adverse events (AEs) leading to treatment discontinuation. [48 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.