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

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ClinicalTrials.gov Identifier: NCT04529772
Recruitment Status : Recruiting
First Posted : August 28, 2020
Last Update Posted : September 21, 2021
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Acerta Pharma BV

Tracking Information
First Submitted Date  ICMJE August 25, 2020
First Posted Date  ICMJE August 28, 2020
Last Update Posted Date September 21, 2021
Actual Study Start Date  ICMJE October 8, 2020
Estimated Primary Completion Date August 31, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 25, 2020)
Progression-free survival (PFS) per the Lugano Classification for NHL in Arm A compared to Arm B [ Time Frame: 60 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 25, 2020)
  • Investigator-assessed event-free survival (EFS) for NHL in Arm A compared to Arm B [ Time Frame: 60 months ]
  • Overall survival in Arm A compared to Arm B [ Time Frame: 60 months ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Combination of Acalabrutinib With R-CHOP in Subjects With Previously Untreated Non-GCB Subtype DLBCL (ACE-LY-312)
Official Title  ICMJE 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
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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Double-blind Randomised Placebo-controlled Study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Participant Care provider Investigator Outcomes assessor
Primary Purpose: Treatment
Condition  ICMJE Diffuse Large B-Cell Lymphoma
Intervention  ICMJE
  • Drug: acalabrutinib
    Investigational Product
  • Drug: placebo
    Placebo comparator
  • Drug: Prednisone
    Investigational Product
  • Drug: Rituximab
    Investigational Product
  • Drug: Cyclophosphamide
    Investigational Product
  • Drug: Vincristine
    Investigational Product
  • Drug: Doxorubicin
    Investigational Product
Study Arms  ICMJE
  • Experimental: acalabrutinib + R-CHOP
    Acalabrutinib plus Rituximab, Cyclosphosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP)
    Interventions:
    • Drug: acalabrutinib
    • Drug: Prednisone
    • Drug: Rituximab
    • Drug: Cyclophosphamide
    • Drug: Vincristine
    • Drug: Doxorubicin
  • Placebo Comparator: placebo + R-CHOP
    Placebo plus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP)
    Interventions:
    • Drug: placebo
    • Drug: Prednisone
    • Drug: Rituximab
    • Drug: Cyclophosphamide
    • Drug: Vincristine
    • Drug: Doxorubicin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 25, 2020)
600
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 31, 2026
Estimated Primary Completion Date August 31, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Brazil,   Canada,   China,   Czechia,   France,   Germany,   India,   Israel,   Italy,   Japan,   Korea, Republic of,   Mexico,   Poland,   Portugal,   Russian Federation,   Spain,   Taiwan,   Turkey,   Ukraine,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04529772
Other Study ID Numbers  ICMJE D8227C00001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Responsible Party Acerta Pharma BV
Study Sponsor  ICMJE Acerta Pharma BV
Collaborators  ICMJE AstraZeneca
Investigators  ICMJE Not Provided
PRS Account Acerta Pharma BV
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP