This study is being carried out around the world to find out if the drug acalabrutinib in combination with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) could help patients with diffuse large B-cell lymphoma.

Phase 3

Recruiting

• Conditions: Diffuse large B-cell lymphoma,

• Registration Number: CTRI/2022/03/041246
• Lead Sponsor: Labcorp Drug Development India Private Limited

Brief Summary

This study will evaluate the safety and efficacy of the small-molecule BTK inhibitor acalabrutinib in combination with R-CHOP, versus placebo plus R-CHOP, in adult subjects ≤65 years of age with previously untreated non-GCB DLBCL. The design and conduct of this study are supported by an understanding of the natural history and current therapies for subjects with DLBCL; knowledge of the activity and safety of the B-cell receptor (BCR) inhibitors (i.e., ibrutinib) in subjects with B-cell malignancies; and the available nonclinical and clinical information regarding acalabrutinib.



Primary objective of this study is to evaluate if the addition of acalabrutinib to R-CHOP prolongs PFS, as compared with placebo plus R-CHOP alone in subjects ≤65 years with previously untreated non-GCB DLBCL (ABC or unclassified) selected by GEP, based on investigator assessed response.



This is a global multicenter study with approximately 250 sites. Subjects will be randomized to study treatment only after GEP-confirmation of non-GCB DLBCL. Approximately 600 subjects with previously untreated non-GBC DLBCL will be randomized in a 1:1 ratio into 2 treatment arms (n=300 subjects each) to receive either acalabrutinib in combination with R-CHOP (Arm A), or placebo in combination with R-CHOP (Arm B).

Detailed Description

Not available

Study Timeline

• Study Start: 2022-03-28
• Last Update Posted: 2023-08-31

Recruitment & Eligibility

• Status: Open to Recruitment
• Sex: All
• Target Recruitment: 600

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 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 or CLL 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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Investigator-assessed event-free survival (EFS) for NHL in Arm A compared to Arm B	Overall survival in Arm A compared to Arm B

Trial Locations

Locations (7)

Amrita Institute of Medical Sciences (AIMS); 🇮🇳 Ernakulam, KERALA, India

Apex Wellness Hospital; 🇮🇳 Nashik, MAHARASHTRA, India

Cytecare Hospitals Pvt Ltd; 🇮🇳 Rural, KARNATAKA, India

Grant Medical Foundation Ruby Hall Clinic; 🇮🇳 Pune, MAHARASHTRA, India

HCG Manavata Cancer Centre; 🇮🇳 Nashik, MAHARASHTRA, India

Manipal Hospital; 🇮🇳 Bangalore, KARNATAKA, India

Tata Memorial Hospital; 🇮🇳 Mumbai, MAHARASHTRA, India

Amrita Institute of Medical Sciences (AIMS)

🇮🇳Ernakulam, KERALA, India

Dr Wesley M Jose

Principal investigator

917025759415

wjose.onco@gmail.com