An Open-label, Phase 2 Study of ACP-196 (Acalabrutinib) in Subjects With Mantle Cell Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to characterize the safety and efficacy profile of ACP-196 (acalabrutinib) in subjects with relapsed or refractory Mantle Cell Lymphoma (MCL).

Detailed Description
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This clinical trial is a Phase 2, multicenter, (approximately 70 global centers), open-label study in subjects with histologically documented MCL, who have relapsed after, or were refractory to, ≥ 1 (but not > 5) prior treatment regimens. Subjects will be enrolled and will take 100 mg of acalabrutinib twice per day (BID) in repeated 28-day cycles. Treatment with acalabrutinib may be continued until disease progression or an unacceptable drug-related toxicity occurs. Dose modification provisions are provided in the study protocol. All subjects will have hematology, chemistry, and urinalysis safety panels done at screening. Once dosing commences (Day 1), all subjects will be evaluated for safety, including serum chemistry and hematology, once weekly for the first 4 weeks, every 2 weeks in Cycle 2, every 4 weeks in Cycles 3 to 12, and every 24 weeks thereafter. PK/PD testing will be done in Cycles 1 and 2. Tumor assessments will be completed at 8- to 24-week intervals during the trial.

Official Title
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An Open-label, Phase 2 Study of ACP-196 in Subjects With Mantle Cell Lymphoma

Conditions
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Mantle Cell Lymphoma (MCL)

Intervention / Treatment
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* Drug: ACP-196 (acalabrutinib)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Men and women ≥ 18 years of age. Pathologically confirmed MCL, with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2. Agreement to use contraception during the study and for 30 days after the last dose of study drugs if sexually active and able to bear or beget children. Exclusion criteria: A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ACP-196 (acalabrutinib), or put the study outcomes at undue risk Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or corrected QT interval (QTc) > 480 msec. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction. Breast feeding or pregnant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACP-196 (acalabrutinib) Regimen 1<br>ACP-196 (acalabrutinib) Regimen 1 | Drug: ACP-196 (acalabrutinib)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) of ACP-196 (Acalabrutinib) in Subjects With Previously Treated MCL. | The overall response rate (ORR) is defined as the proportion of subjects achieving either a partial remission (response) (PR) or complete response (CR) according to the Lugano Classification for NHL (Cheson 2014) as assessed by investigators, where SD stands for Stable Disease, PD for Progressive Disease and NE for Not Evaluable. | From the date of the first dose until 30 days after the last dose of the study drug or start of a new anti-cancer treatment, whichever came first, assessed up to approximately 4 year and 10 months. 1 cycle =28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bruton tyrosine kinase inhibitor, Btk, Mantle Cell Lymphoma, MCL, ACP-196, Acalabrutinib, ACE-LY-004, Calquence