| CTRI Number |
CTRI/2022/03/041246 [Registered on: 22/03/2022] Trial Registered Prospectively |
| Last Modified On: |
02/04/2026 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
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. |
Scientific Title of Study
Modification(s)
|
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Acalabrutinib in Combination with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Subjects ≤75 Years with Previously Untreated Non-Germinal Center Diffuse Large B-Cell Lymphoma |
| Trial Acronym |
ESCALADE |
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| ACE-LY-312 (D8227C00001) V9.0 dated 29-Apr-2025 |
Protocol Number |
| NCT04529772 |
ClinicalTrials.gov |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Shekhar Dawkhar |
| Designation |
Senior Director |
| Affiliation |
Labcorp Drug Development India Private Limited |
| Address |
Labcorp Drug Development India Private Limited, Bld No. 1, Unit No. 601, Raheja Mindspace, Plot No. Gen21D,EandF at MIDCTTC, Shiravane, Nerul, Navi Mumbai, Maharashtra
Mumbai (Suburban)
MAHARASHTRA
400706
India |
| Phone |
912268221500 |
| Fax |
|
| Email |
shekhar.dawkhar@labcorp.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Shekhar Dawkhar |
| Designation |
Senior Director |
| Affiliation |
Labcorp Drug Development India Private Limited |
| Address |
Labcorp Drug Development India Private Limited, Bld No. 1, Unit No. 601, Raheja Mindspace, Plot No. Gen21D,EandF at MIDCTTC, Shiravane, Nerul, Navi Mumbai, Maharashtra
MAHARASHTRA
400706
India |
| Phone |
912268221500 |
| Fax |
|
| Email |
shekhar.dawkhar@labcorp.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Shekhar Dawkhar |
| Designation |
Senior Director |
| Affiliation |
Labcorp Drug Development India Private Limited |
| Address |
Labcorp Drug Development India Private Limited, Bld No. 1, Unit No. 601, Raheja Mindspace, Plot No. Gen21D,EandF at MIDCTTC, Shiravane, Nerul, Navi Mumbai, Maharashtra
MAHARASHTRA
400706
India |
| Phone |
912268221500 |
| Fax |
|
| Email |
shekhar.dawkhar@labcorp.com |
|
|
Source of Monetary or Material Support
|
| Labcorp Drug Development India Private Limited |
|
|
Primary Sponsor
|
| Name |
Labcorp Drug Development India Private Limited |
| Address |
Labcorp Drug Development India Private Limited, Building No. 1, Unit No. 601, Raheja Mindspace, Plot Nos. Gen,2,1,D,E,F at MIDCTTC Industrial Area, Shiravane, Nerul, Navi Mumbai, Maharashtra 400706, India. |
| Type of Sponsor |
Contract research organization |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| Acerta Pharma BV |
Acerta Pharma B.V., A Member of the AstraZeneca Group, Kloosterstraat 9, 5349 AB Oss, The Netherlands |
|
|
Countries of Recruitment
|
Australia
Austria
Belgium
Brazil
Canada
China
Czech Republic
France
Germany
India
Israel
Italy
Japan
Mexico
Poland
Portugal
Republic of Korea
Russian Federation
Spain
Taiwan
Turkey
Ukraine
United States of America |
Sites of Study
Modification(s)
|
| No of Sites = 7 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Sameer Bakhshi |
All India Institute of Medical Sciences |
Department of Medical Oncology, Room # 243, 2nd floor, Dr. BRA IRCH AIIMS, Ansari Nagar, New Delhi 110029, India
New Delhi
DELHI |
01129575237
sambakh@hotmail.com |
| Dr Wesley M Jose |
Amrita Institute of Medical Sciences (AIMS) |
Dept of Medical Oncology and Haematology, AIMS Ponekkara P.O., Cochin 682041, Kerala, India
Ernakulam
KERALA |
917025759415
wjose.onco@gmail.com |
| Dr Shailesh Bondarde |
Apex Wellness Hospital |
Survey No 799, Plot No l87, Behind Prakash petrol pump, Govind Nagar, Nashik 422009, Maharashtra, India.
Nashik
MAHARASHTRA |
919822012427
shaileshbondarde1971@gmail.com |
| Dr Prasad Narayanan |
Cytecare Hospitals Pvt Ltd |
Cytecare Hospitals Pvt Ltd, Venkatala, Near Bagalur Cross, Yelahanka, Bengaluru Rural, Karnataka – 560064, India
Bangalore Rural
KARNATAKA |
918884122456
prasad.narayanan@cytecare.com |
| Dr Madatha Vijay Ramanan |
Grant Medical Foundation Ruby Hall Clinic |
Cancer Building, 1st floor, room 103, 40, Sassoon Road, Pune 411001, Maharashtra, India
Pune
MAHARASHTRA |
919325315471
mvijayr@gmail.com |
| Dr Rajnish Nagarkar |
HCG Manavata Cancer Centre |
1st floor, MCRI department, Behind Shivang Auto, Mumbai Naka, Nashik 422001, Maharashtra, India
Nashik
MAHARASHTRA |
02536661111
drraj@manavatacancercentre.com |
| Dr Bhausaheb Bagal |
Tata Memorial Hospital |
Adult Hematolymphoid Unit, OPD 81, Main Building, Ground Floor, Dr. E. Borges Road, Parel, Mumbai-400012, Maharashtra, India
Mumbai
MAHARASHTRA |
919930428999
bagalbp@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 7 |
| Name of Committee |
Approval Status |
| Apex Wellness Ethics Committee |
Approved |
| Cytecare Institutional Ethics Committee |
Approved |
| Institute Ethics Committee - All India Institute of Medical Sciences |
Approved |
| Institutional Ethics Committee, Amrita Institute of Medical Sciences |
Approved |
| Institutional Ethics Committee, Poona Medical Research Foundation |
Approved |
| Institutional Review Board, TATA Memorial Hospital |
Approved |
| Manavata Clinical Research Institute, Ethics Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C833||Diffuse large B-cell lymphoma, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Acalabrutinib |
Dose: 200 mg per day,
Dose Frequency: 1 x 100 mg capsule BID (Twice a day, Every 12 Hours),
Route of administration: Oral,
Duration of therapy: 8 Cycles of 21 days (i.e 168 days). |
| Comparator Agent |
Placebo |
Dose: NA,
Dose Frequency: 1 x 100 mg capsule BID (Twice a day, Every 12 Hours),
Route of administration: Oral,
Duration of therapy: 8 Cycles of 21 days (i.e 168 days) |
|
Inclusion Criteria
Modification(s)
|
| Age From |
18.00 Year(s) |
| Age To |
75.00 Year(s) |
| Gender |
Both |
| Details |
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 |
|
| ExclusionCriteria |
| Details |
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. |
|
|
Method of Generating Random Sequence
|
Stratified randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Participant and Investigator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| 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
|
| Outcome |
TimePoints |
Investigator-assessed event-free survival (EFS) for NHL in Arm A compared to Arm B
Overall survival in Arm A compared to Arm B
Percentage of Participants Who Achieved a Complete Response (CR) per 2014 Lugano Classification at the end of study treatment |
At every single visit up to 60 months |
|
|
Target Sample Size
|
Total Sample Size="600"
Sample Size from India="61"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
28/03/2022 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
08/10/2020 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="8"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Closed to Recruitment of Participants |
| Recruitment Status of Trial (India) |
Closed to Recruitment of Participants |
|
Publication Details
|
NIL |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
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). |