Diffuse Large B-Cell Lymphoma
Conditions
Keywords
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
Brief summary
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
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).
Interventions
DRUGacalabrutinib
Investigational Product
DRUGplacebo
Placebo comparator
DRUGPrednisone
Investigational Product
DRUGRituximab
Investigational Product
DRUGCyclophosphamide
Investigational Product
DRUGVincristine
Investigational Product
DRUGDoxorubicin
Investigational Product
Sponsors
Acerta Pharma BV
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Participant Care provider Investigator Outcomes assessor
Intervention model description
Double-blind Randomised Placebo-controlled Study
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Countries
Australia, Austria, Belgium, Brazil, Canada, China, Czechia, France, Germany, India, Israel, Italy, Japan, Mexico, Poland, Portugal, Russia, South Korea, Spain, Taiwan, Turkey (Türkiye), Ukraine, United States
Outcome results
None listed