Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04529772
Recruitment Status : Recruiting
First Posted : August 28, 2020
Last Update Posted : July 27, 2021
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Diffuse Large B-Cell Lymphoma Drug: acalabrutinib Drug: placebo Drug: Prednisone Drug: Rituximab Drug: Cyclophosphamide Drug: Vincristine Drug: Doxorubicin Phase 3

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).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 600 participants
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
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
Actual Study Start Date : October 8, 2020
Estimated Primary Completion Date : August 31, 2026
Estimated Study Completion Date : August 31, 2026


Arm Intervention/treatment
Experimental: acalabrutinib + R-CHOP
Acalabrutinib plus Rituximab, Cyclosphosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP)
Drug: acalabrutinib
Investigational Product

Drug: Prednisone
Investigational Product

Drug: Rituximab
Investigational Product

Drug: Cyclophosphamide
Investigational Product

Drug: Vincristine
Investigational Product

Drug: Doxorubicin
Investigational Product

Placebo Comparator: placebo + R-CHOP
Placebo plus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP)
Drug: placebo
Placebo comparator

Drug: Prednisone
Investigational Product

Drug: Rituximab
Investigational Product

Drug: Cyclophosphamide
Investigational Product

Drug: Vincristine
Investigational Product

Drug: Doxorubicin
Investigational Product




Primary Outcome Measures :
  1. Progression-free survival (PFS) per the Lugano Classification for NHL in Arm A compared to Arm B [ Time Frame: 60 months ]

Secondary Outcome Measures :
  1. Investigator-assessed event-free survival (EFS) for NHL in Arm A compared to Arm B [ Time Frame: 60 months ]
  2. Overall survival in Arm A compared to Arm B [ Time Frame: 60 months ]
  3. 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04529772


Contacts
Layout table for location contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
Show Show 257 study locations
Sponsors and Collaborators
Acerta Pharma BV
AstraZeneca
Layout table for additonal information
Responsible Party: Acerta Pharma BV
ClinicalTrials.gov Identifier: NCT04529772    
Other Study ID Numbers: D8227C00001
First Posted: August 28, 2020    Key Record Dates
Last Update Posted: July 27, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
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
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

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Acerta Pharma BV:
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Prednisone
Cyclophosphamide
Rituximab
Doxorubicin
Vincristine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents