A Study of BR Alone Versus in Combination With Acalabrutinib in Subjects With Previously Untreated MCL

Conditions

Lymphoma, Mantle Cell

Keywords

Bruton tyrosine kinase inhibitor, Acalabrutinib, Mantle Cell Lymphoma, ACE-LY-308, Treatment naive, non-Hodgkins Lymphoma, Bendomustine, Rituximab

Brief summary

This study is evaluating the efficacy of acalabrutinib in combination with bendamustine and rituximab (BR) compared with placebo plus BR in subjects with previously untreated mantle cell lymphoma.

Detailed description

To evaluate the efficacy of acalabrutinib in combination with bendamustine and rituximab (BR) compared with placebo plus BR based on Independent Review Committee (IRC) assessment of progression-free survival (PFS) per the Lugano Classification for Non-Hodgkin Lymphoma (NHL) in subjects with previously untreated mantle cell lymphoma (MCL).

Michael Wang, Jonas Paludo, João Samuel de Holanda Farias, Diego Villa, Cecily Forsyth et al. (11 authors)

Blood2025-11-03

10.1182/blood-2025-885

Analysis of predictive factors for POD24 in patients with previously untreated mantle cell lymphoma receiving bendamustine-rituximab with or without acalabrutinib in the phase 3 ECHO trial

Chan Y. Cheah, Stephen E. Spurgeon, Sung‐Soo Yoon, Mélina Boutin, Eva González‐Barca et al. (10 authors)

Blood2025-11-03

10.1182/blood-2025-3578

High-Risk Subgroups and MRD: An Updated Analysis of the Phase 3 ECHO Trial of Acalabrutinib with Bendamustine/Rituximab in Previously Untreated Mantle Cell Lymphoma

Martin Dreyling, Jiřı́ Mayer, David Belada, Yuqin Song, Wojciech Jurczak et al. (20 authors)

Blood2024-11-056 citations

10.1182/blood-2024-200290

A phase 2, multicentre, open‐label trial (<scp>ACE‐LY</scp>‐003) of acalabrutinib in patients with relapsed or refractory marginal zone lymphoma

Paolo Strati, Morton Coleman, Rebecca Champion, Shuo Ma, Caterina Patti et al. (12 authors)

British Journal of Haematology2022-07-2128 citations

10.1111/bjh.18368

A PHASE 3 STUDY OF ACALABRUTINIB PLUS BENDAMUSTINE AND RITUXIMAB IN ELDERLY (AGED ≥65 Years) TREATMENT‐NAIVE PATIENTS WITH MANTLE CELL LYMPHOMA

M. Wang, David Belada, Chan Y. Cheah, MH Chu, Martin Dreyling et al. (20 authors)

Hematological Oncology2019-06-012 citations

10.1002/hon.2632

Safety and Efficacy of Acalabrutinib Plus Bendamustine and Rituximab (BR) in Patients with Treatment-Naive (TN) or Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL)

Tycel Phillips, Stephen D. Smith, Wojciech Jurczak, Tadeusz Robak, Don A. Stevens et al. (19 authors)

Blood2018-11-297 citations

10.1182/blood-2018-99-110617

Interventions

DRUGAcalabrutinib

Administered orally (PO)

DRUGBendamustine

Administered intravenously (IV)

DRUGRituximab

Administered intravenously (IV)

DRUGPlacebo

Placebo comparator

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

65 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* Men and women, ≥ 65 years of age. * Pathologically confirmed MCL, with documentation of a chromosome translocation t(11;14)(q13;q32) and/or overexpression of cyclin D1 in association with other relevant markers (eg, CD5, CD19, CD20, PAX5) . * MCL requiring treatment and for which no prior systemic anticancer therapies have been received. * Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2. * Agreement to use highly effective forms of contraception during the study and 6 months after the last dose of bendamustine, or 12 months after the last dose of rituximab, whichever is longest .

Exclusion criteria

* 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, or corrected QT interval (QTc) \> 480 msec (calculated using Friderica's formula: QT/RR0.33) at screening. Exception: Subjects with controlled, asymptomatic atrial fibrillation during screening are allowed to enroll on study. * 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 (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment), or intravenous anti infective treatment within 2 weeks before first dose of study drug. * Concurrent participation in another therapeutic clinical trial.

Design outcomes

Primary

Measure	Time frame	Description
Progression-free survival per the Lugano Classification for NHL in Arm 1 compared to Arm 2	Up to 6 years	Defined as the time from the date of randomization until disease progression (assessed by the IRC per the Lugano Classification for NHL) or death from any cause, whichever occurs first.

Secondary

Measure	Time frame	Description
Investigator-assessed progression-free survival per the Lugano Classification for NHL in Arm 1 compared to Arm 2	Up to 6 years	Defined as the time from the date of randomization until disease progression (assessed by the investigator per the Lugano Classification for NHL) or death from any cause, whichever occurs first.
Investigator-assessed overall response rate per the Lugano Classification for NHL in Arm 1 compared to Arm 2	Up to 6 years	Defined as the proportion of subjects who achieve either partial response (PR) or complete response (CR) as best overall response according to the Lugano Classification for NHL as assessed by investigator.
IRC-assessed overall response rate per the Lugano Classification for NHL in Arm 1 compared to Arm 2	Up to 6 years	Defined as the proportion of subjects who achieve either PR or CR as best overall response according to the Lugano Classification for NHL as assessed by IRC.
Overall survival in Arm 1 compared to Arm 2	Up to 6 years	Defined as the time from randomization until the date of death from any cause.
IRC-assessed duration of response per the Lugano Classification for NHL in Arm 1 compared to Arm 2	Up to 6 years	Defined as the time from the first documentation of CR or PR to disease progression per the Lugano Classification for NHL or death from any cause, whichever occurs first.
IRC assessed time to response per the Lugano Classification for NHL in Arm 1 compared to Arm 2	Up to 6 years	Defined as the time from randomization to the first CR or PR per the Lugano Classification for NHL.

Countries

Argentina, Australia, Belgium, Brazil, Canada, China, Czechia, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Mexico, New Zealand, Peru, Poland, Romania, Russia, South Korea, Spain, Taiwan, Ukraine, United States, Vietnam

Outcome results

None listed