A Study of Acalabrutinib in Combination With Rituximab + (Bendamustine or Venetoclax) in Subjects With MCL

Study Overview
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Brief Summary
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A Phase 1b, Multicenter, Open-label Study of Acalabrutinib in Combination with Bendamustine and Rituximab (BR) or Venetoclax and Rituximab (VR) in Subjects with Mantle Cell Lymphoma

Detailed Description
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This is a multicenter, open-label Phase 1b study to assess the safety and efficacy of acalabrutinib when administered concomitantly with bendamustine and rituximab in subjects with treatment naive or relapse refractory mantle cell lymphoma (Part 1), or when administered concomitantly with venetoclax and rituximab in subjects with treatment naive mantle cell lymphoma (Part 2).

Official Title
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A Phase 1b, Multicenter, Open-label Study of Acalabrutinib in Combination With Bendamustine and Rituximab (BR) or Venetoclax and Rituximab (VR) in Subjects With Mantle Cell Lymphoma

Conditions
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Mantle Cell Lymphoma (MCL)

Intervention / Treatment
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* Drug: Acalabrutinib in combination with BR
* Drug: Acalabrutinib in combination with VR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women ≥ 18 years of age. Pathologically confirmed MCL. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2. Agreement to use highly effective forms of contraception during the study and for 2 days after the last dose of acalabrutinib, 30 days after the last dose of venetoclax, or 12 months after the last dose of rituximab, whichever is longest. Treatment Naive MCL patients requiring treatment with no exposure to prior therapies. Exclusion Criteria: Significant cardiovascular disease such as uncontrolled or untreated 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.Exception: Subjects with controlled, asymptomatic atrial fibrillation during screening are allowed to enroll on study Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, 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 (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment), or intravenous anti-infective treatment within 2 weeks before first dose of study drug Breastfeeding or pregnant Concurrent participation in another therapeutic clinical trial.
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+BR in TN patients<br>Part 1: Acalabrutinib in combination with drugs bendamustine and rituximab (BR) in treatment naive patients | Drug: Acalabrutinib in combination with BR<br> <br> * Other names: Acalabrutinib + BR;|
| Experimental: Part 1: Acalabrutinib+BR in RR patients<br>Part 1: Acalabrutinib in combination with bendamustine and rituximab (BR) in relapse refractory patients | Drug: Acalabrutinib in combination with BR<br> <br> * Other names: Acalabrutinib + BR;|
| Experimental: Part 2: Acalabrutinib+VR in TN patients<br>Part 2: Acalabrutinib in combination with venetoclax and rituximab (VR) in treatment naive patients | Drug: Acalabrutinib in combination with VR<br> <br> * Other names: Acalabrutinib + VR;|

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) as assessed by CTCAE v4.03 | 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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Bruton Tyrosine Kinase Inhibitor, BTK, Mantle Cell Lymphoma, MCL, Acalabrutinib, ACE-LY-106