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

Acerta Pharma

Status and phase

Active, not recruiting

Phase 3

Conditions

Lymphoma, Mantle Cell

Treatments

Drug: Bendamustine

Drug: Acalabrutinib

Drug: Rituximab

Drug: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT02972840

ACE-LY-308

2015-005220-26 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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).

Enrollment

635 patients

Sex

All

Ages

65+ years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

635 participants in 2 patient groups, including a placebo group

Acalabrutinib in combination with bendamustine and rituximab

Experimental group

Description:

Acalabrutinib administered twice per day (BID) orally (PO) plus bendamustine on Days 1 and 2 and rituximab on Day 1; cycles are repeated every 28 days.

Treatment:

Drug: Rituximab

Drug: Acalabrutinib

Drug: Bendamustine

Placebo in combination with bendamustine and rituximab

Placebo Comparator group

Description:

Matching placebo administered BID PO plus bendamustine on Days 1 and 2 and rituximab on Day 1; cycles are repeated every 28 days.

Treatment:

Drug: Placebo

Drug: Rituximab

Drug: Bendamustine