Study of Acalabrutinib Alone or in Combination Therapy in Subjects With B-cell Non-Hodgkin Lymphoma

Study Overview
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Brief Summary
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Part 1: To characterize the safety profile of acalabrutinib alone or in combination with rituximab in subjects with R/R FL. Part 2: To characterize the activity of acalabrutinib alone or in combination with rituximab in subjects with R/R MZL, as measured by ORR. Part 3: To characterize the safety of acalabrutinib in combination with rituximab and lenalidomide in subjects with R/R FL

Detailed Description
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An Open-label, Phase 1b/2 Study of Acalabrutinib Alone or in Combination Therapy in Subjects with B-cell Non-Hodgkin Lymphoma

Official Title
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An Open-label, Phase 1b/2 Study of Acalabrutinib Alone or in Combination Therapy in Subjects With B-cell Non-Hodgkin Lymphoma

Conditions
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Non Hodgkin Lymphoma

Intervention / Treatment
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* Drug: acalabrutinib
* Drug: rituximab (IV)
* Drug: Lenalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women ≥ 18 years of age. Part 1: A confirmed diagnosis of FL Grade 1, 2, or 3a, which has relapsed after, or been refractory to ≥ 1 prior therapy for FL, or subjects who have not previously received systemic anticancer therapy for FL., and which requires treatment. Part 2: For subject with relapsed or refractory MZL: Histologically confirmed MZL including splenic, nodal, and extranodal sub-types Subjects with splenic MZL must have an additional measurable lesion, nodal or extranodal, as described in inclusion criterion #4; Subjects with gastric mucosa-associated lymphoid tissue (MALT) lymphoma must be Helicobacter pylori (HP)-negative Part 3: For subjects with FL: Pathologically confirmed diagnosis of FL Grade 1, 2, or 3a, which has relapsed after, or been refractory to ≥ 1 prior therapy for FL and which requires treatment per National Cancer Institute or ESMO clinical practice guidelines. 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 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 Qtc >480 msec Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, gastric bypass, 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

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: acalabrutinib Regimen 1<br>acalabrutinib Regimen 1 for relapsed, refractory Follicular Lymphoma subjects | Drug: acalabrutinib<br> <br> * Other names: ACP-196;|
| Experimental: Part 1: acalabrutinib Regimen 2<br>acalabrutinib Regimen 2 + rituximab for relapsed, refractory, or treatment naive Follicular Lymphoma subjects | Drug: acalabrutinib<br> <br> * Other names: ACP-196;Drug: rituximab (IV)<br> <br> |
| Experimental: Part 2: acalabrutinib Regimen 1<br>acalabrutinib Regimen 1 for relapsed, refractory Marginal Zone Lymphoma subjects | Drug: acalabrutinib<br> <br> * Other names: ACP-196;|
| Experimental: Part 2: acalabrutinib Regimen 2<br>acalabrutinib Regimen 2 + rituximab for relapsed, refractory Marginal Zone Lymphoma subjects | Drug: acalabrutinib<br> <br> * Other names: ACP-196;Drug: rituximab (IV)<br> <br> |
| Experimental: Part 3: acalabrutinib Regimen 1<br>acalabrutinib Regimen + lenalidomide + rituximab for relapsed, refractory Follicular Lymphoma subjects | Drug: acalabrutinib<br> <br> * Other names: ACP-196;Drug: rituximab (IV)<br> <br> Drug: Lenalidomide<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (AEs) | Number of participants who had experienced at least one treatment emergent AE | From first dose of study drug to within 30 days of last dose of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MZL, Bruton tyrosine kinase inhibitor, Btk, Follicular Lymphoma, FL, acalabrutinib, ACP-196, Marginal Zone Lymphoma