A Combination of Acalabrutinib With R-CHOP in Subjects With Previously Untreated Non-GCB DLBCL (ACE-LY-312)

Study Overview
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Brief Summary
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Phase 3 randomized, double-blind, placebo-controlled, study assessing the efficacy and safety of acalabrutinib plus rituximab,cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) vs placebo plus R-CHOP in subjects ≤75 years of age with previously untreated non-germinal center diffuse large B-cell lymphoma.

Detailed Description
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Phase 3 randomized, double-blind, placebo-controlled, study to evaluate the efficacy and safety of acalabrutinib plus rituximab,cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as compared with placebo plus R-CHOP in subjects ≤75 years of age with previously untreated non-germinal center diffuse large B-cell lymphoma (activated B-cell (ABC) and unclassified).

Official Title
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Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Acalabrutinib in Combination With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Subjects ≤75 Years With Previously Untreated Non-GCB DLBCL

Conditions
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Diffuse Large B-Cell Lymphoma

Intervention / Treatment
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* Drug: acalabrutinib
* Drug: placebo
* Drug: Prednisone
* Drug: Rituximab
* Drug: Cyclophosphamide
* Drug: Vincristine
* Drug: Doxorubicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women, age ≥18 and ≤75 years Pathologically confirmed DLBCL, sufficient diagnostic material should be available to forward to a central laboratory for gene expression profiling and pathology review. No prior treatment for DLBCL Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2. International Prognostic Index (IPI) score of 1 to 5 Disease Stage II to IV by the Ann Arbor Classification Adequate organ and marrow function Agreement to use highly effective forms of contraception during the study and 12 months after the last dose of rituximab Exclusion Criteria: Evidence of severe or uncontrolled systemic diseases Known history of a bleeding diathesis (i.e., haemophilia, von Willebrand disease) History of stroke or intracranial haemorrhage in preceding 6 months. Known CNS lymphoma or leptomeningeal disease Known primary mediastinal lymphoma Known High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements Prior history of indolent lymphoma or CLL History of or ongoing confirmed PML Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of first dose of study drug, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification 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 Prior anthracycline use ≥150 mg/m2

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Interventional Model Description: Double-blind Randomised Placebo-controlled Study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: acalabrutinib + R-CHOP<br>Acalabrutinib plus Rituximab, Cyclosphosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP) | Drug: acalabrutinib<br>* Investigational Product<br>Drug: Prednisone<br>* Investigational Product<br>Drug: Rituximab<br>* Investigational Product<br>Drug: Cyclophosphamide<br>* Investigational Product<br>Drug: Vincristine<br>* Investigational Product<br>Drug: Doxorubicin<br>* Investigational Product<br>|
| Placebo Comparator: placebo + R-CHOP<br>Placebo plus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP) | Drug: placebo<br>* Placebo comparator<br>Drug: Prednisone<br>* Investigational Product<br>Drug: Rituximab<br>* Investigational Product<br>Drug: Cyclophosphamide<br>* Investigational Product<br>Drug: Vincristine<br>* Investigational Product<br>Drug: Doxorubicin<br>* Investigational Product<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) per the Lugano Classification for NHL in Arm A compared to Arm B |  | at every single visit up to 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator-assessed event-free survival (EFS) for NHL in Arm A compared to Arm B |  | at every single visit up to 60 months | 
| Overall survival in Arm A compared to Arm B |  | at every single visit up to 60 months | 
| Percentage of Participants Who Achieved a Complete Response (CR) per 2014 Lugano Classification for NHL |  | at every single visit up to 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Untreated Non-Germinal Center Diffuse Large B-Cell Lymphoma, Lymphoma, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Neoplasms, Lymphoproliferative Disorders, Lymphatic Diseases, Lymphoma, Non-Hodgkin, Prednisone, Cyclophosphamide, Rituximab, Doxorubicin, Vincristine, Acalabrutinib, Calquence