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

Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Acalabrutinib in Combination With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Subjects ≤65 Years With Previously Untreated Non-Germinal Center DLBCL

Sponsors

Lead Sponsor: Acerta Pharma BV

Collaborator: AstraZeneca

Source Acerta Pharma BV
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 ≤65 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 ≤65 years of age with previously untreated non-germinal center diffuse large B-cell lymphoma (activated B-cell (ABC) and unclassified).

Overall Status Not yet recruiting
Start Date September 30, 2020
Completion Date August 31, 2026
Primary Completion Date August 31, 2026
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Progression-free survival (PFS) per the Lugano Classification for NHL in Arm A compared to Arm B 60 months
Secondary Outcome
Measure Time Frame
Investigator-assessed event-free survival (EFS) for NHL in Arm A compared to Arm B 60 months
Overall survival in Arm A compared to Arm B 60 months
Percentage of Participants Who Achieved a Complete Response (CR) per 2014 Lugano Classification at the end of study treatment Up to 32 weeks
Enrollment 600
Condition
Intervention

Intervention Type: Drug

Intervention Name: acalabrutinib

Description: Investigational Product

Arm Group Label: acalabrutinib + R-CHOP

Intervention Type: Drug

Intervention Name: placebo

Description: Placebo comparator

Arm Group Label: placebo + R-CHOP

Intervention Type: Drug

Intervention Name: Prednisone

Description: Investigational Product

Intervention Type: Drug

Intervention Name: Rituximab

Description: Investigational Product

Intervention Type: Drug

Intervention Name: Cyclophosphamide

Description: Investigational Product

Intervention Type: Drug

Intervention Name: Vincristine

Description: Investigational Product

Intervention Type: Drug

Intervention Name: Doxorubicin

Description: Investigational Product

Eligibility

Criteria:

Inclusion Criteria: - Men and women, age ≥18 and ≤65 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 2 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 - History of or ongoing confirmed progressive multifocal leukoencephalopathy - 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 - Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer. - Requires treatment with proton pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Patients receiving proton pump inhibitors who switch to short-acting H2-receptor antagonists or antacids are eligible for enrolment into this study.

Gender: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Healthy Volunteers: No

Overall Contact

Last Name: AstraZeneca Clinical Study Information Center

Phone: 1-877-240-9479

Email: [email protected]

Verification Date

August 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: acalabrutinib + R-CHOP

Type: Experimental

Description: Acalabrutinib plus Rituximab, Cyclosphosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP)

Label: placebo + R-CHOP

Type: Placebo Comparator

Description: Placebo plus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP)

Acronym ESCALADE
Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Intervention Model Description: Double-blind Randomised Placebo-controlled Study

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description: Participant Care provider Investigator Outcomes assessor

Source: ClinicalTrials.gov