Clinical Trials /

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

NCT04529772

Description:

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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: D8227C00001
  • NCT ID: NCT04529772

Conditions

  • Diffuse Large B-Cell Lymphoma

Interventions

DrugSynonymsArms
acalabrutinibacalabrutinib + R-CHOP
placeboplacebo + R-CHOP
Prednisoneacalabrutinib + R-CHOP
Rituximabacalabrutinib + R-CHOP
Cyclophosphamideacalabrutinib + R-CHOP
Vincristineacalabrutinib + R-CHOP
Doxorubicinacalabrutinib + R-CHOP

Purpose

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).
    

Trial Arms

NameTypeDescriptionInterventions
acalabrutinib + R-CHOPExperimentalAcalabrutinib plus Rituximab, Cyclosphosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP)
  • acalabrutinib
  • Prednisone
  • Rituximab
  • Cyclophosphamide
  • Vincristine
  • Doxorubicin
placebo + R-CHOPPlacebo ComparatorPlacebo plus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP)
  • placebo
  • Prednisone
  • Rituximab
  • Cyclophosphamide
  • Vincristine
  • Doxorubicin

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.
      
Maximum Eligible Age:65 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS) per the Lugano Classification for NHL in Arm A compared to Arm B
Time Frame:60 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Investigator-assessed event-free survival (EFS) for NHL in Arm A compared to Arm B
Time Frame:60 months
Safety Issue:
Description:
Measure:Overall survival in Arm A compared to Arm B
Time Frame:60 months
Safety Issue:
Description:
Measure:Percentage of Participants Who Achieved a Complete Response (CR) per 2014 Lugano Classification at the end of study treatment
Time Frame:Up to 32 weeks
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Acerta Pharma BV

Trial 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

Last Updated

November 6, 2020