A Study of Bendamustine and Rituximab (BR) Alone Versus in Combination with Acalabrutinib (ACP-196) in Subjects with Previously Untreated Mantle Cell Lymphoma

• Register: REBEC
• Last refreshed on: 29 May 2023
• Main ID: RBR-2xt4yk
• Date of registration: 30/01/2018
• Prospective Registration: No
• Primary sponsor: Hospital São Rafael/Monte Tabor-BA
• Public title: A Study of Bendamustine and Rituximab (BR) Alone Versus in Combination with Acalabrutinib (ACP-196) in Subjects with Previously Untreated Mantle Cell Lymphoma
• Scientific title: A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study of Bendamustine and Rituximab (BR) Alone Versus in Combination with Acalabrutinib (ACP-196) in Subjects with Previously Untreated Mantle Cell Lymphoma
• Date of first enrolment: 01/11/2017
• Recruitment status: Recruiting
• URL: http://ensaiosclinicos.gov.br/rg/RBR-2xt4yk
• Study type: Intervention
• Study design: Clinical Trial of treatment, randomized-controlled, parallel, double-blind, two arms, phase 3
• Phase: 3

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Canada, Czech Republic, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Mexico, New Zealand, Peru, Poland, Republic of Korea, Romania, Russian Federation, Spain, Taiwan, Ukraine, United States, Viet Nam

Contacts

• Name: Cynthia Ventura
• Affiliation: INC Research

• Name: Cynthia Ventura
• Affiliation: INC Research

Key inclusion & exclusion criteria

Inclusion criteria: Men and women, >65 years of age;
Pathologically confirmed MCL, with documentation of monoclonal CD20+ B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1;
MCL requiring treatment and for which no prior systemic anticancer therapies have been received;
Presence of radiologically measurable lymphadenopathy or extranodal lymphoid malignancy (as defined by Lugano Classification for NHL);
Eastern Cooperative Oncology Group (ECOG) performance status of < 2
Men who are sexually active and can beget children must agree to use highly effective forms of contraception during the study and for 90 days after the last dose of acalabrutinib, 6 months after the last dose of bendamustine, or 12 months after the last dose of rituximab, whichever is longest;
Men must agree to refrain from sperm donation during the study and for 90 days after the last dose of acalabrutinib, 6 months after the last dose of endamustine, or 12 months after the last dose of rituximab, whichever is longest; Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty;
Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local patient privacy regulations)

Exclusion criteria: History of prior malignancy except for the following:
Malignancy treated with curative intent and with no evidence of active disease present for more than 2 years before screening and felt to be at low risk for recurrence by treating physician;
Note: Provided they meet other eligibility criteria, subjects who are receiving hormonal therapy alone are allowed to enroll on study;
Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled nonmelanomatous skin cancer;
Adequately treated carcinoma in situ without current evidence of disease;
Subjects for whom the goal of therapy is tumor debulking before stem cell transplant;
Any history of central nervous system (CNS) lymphoma or leptomeningeal disease;
Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP);
Major surgical procedure within 28 days before first dose of study drug. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the
intervention before the first dose of study drug;
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;
Absolute neutrophil count (ANC) < 1.0 x 109/L or platelet count < 75 x 109/L; for subjects with disease involvement in the bone marrow, ANC < 0.75 x 109/L or platelet count < 50 x 109/L. Subjects will only be considered eligible if peripheral blood counts can be
maintained independent of growth factors or transfusions during the screening period;
Total bilirubin > 1.5 x upper limit of normal (ULN); or aspartate aminotransferase (AST) or
alanine aminotransferase (ALT) > 2.5 x ULN;
Estimated creatinine clearance of < 50 mL/min, calculated using the formula of Cockcroft and Gault [(140-Age) • Mass (kg)/(72 • creatinine mg/dL) • multiply by 0.85 if female];
Prothrombin time/international normalized ratio (INR) or activated partial thromboplastin time (aPTT; in the absence of a Lupus anticoagulant) > 2.0 x ULN; Exception: Subjects receiving
warfarin are excluded; however, those receiving other anticoagulant therapy who have a higher INR/aPTT may be permitted to enroll to this study after discussion
with the medical monitor;
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;
Known history of infection with human immunodeficiency virus (HIV);
Ongoing immunosuppressive therapy, including systemic (eg, IV or oral) corticosteroids within 2 weeks before t

Age minimum:
Age maximum:
Gender: -

Health Condition(s) or Problem(s) studied

C04.557.386.480.525

Mantle Cell Lymphoma

Intervention(s)

Approximately 546 subjects in the world meeting the eligibility criteria for the study will be randomized
1:1
Arm 1 - 273 patients: Acalabrutinib administered 100 mg twice per day orally plus bendamustine 90 mg/m2 intravenously on Days 1 and 2 and rituximab 375 mg/m2 intravenous on Day 1; cycles are repeated every 28 days.
Arm 2 - 273 patients: Matching placebo administered twice per day orally plus bendamustine 90 mg/m2 IV on Days 1 and 2 and rituximab 375 mg/m2 intravenously on Day 1; cycles are repeated every 28 days.
For Brazil there are 35 patients designated, each site with the enrollment of 03 patients. The information with the number of participants per intervention was only reported for global data.

Drug

N04.452.706.477

D12.776.124.486.485.114.224

D27.505.954.248

Primary Outcome(s)

Evaluation of Progression free survive (PFS) assessed by Independent Review Committee per the Lugano Classification. A comparison of PFS between Arm One (acalabrutinib plus
BR) and Arm Two (placebo plus BR) will be made, 68 months after the first subject is randomized.

Secondary Outcome(s)

Evaluate the acalabrutinib plus
rituximab in terms of investigator-assessed progression free survive per the Lugano Classification;
Investigator-assessed overall response rate per the Lugano Classification;
IRC-assessed ORR per the Lugano Classification; Overall Survive;
IRC-assessed DOR per the Lugano Classification for NHL;
IRC-assessed TTR per the Lugano Classification for NHL

Source(s) of Monetary Support

Acerta Pharma, BV

Secondary Sponsor(s)

INC Research

Acerta Pharma, BV