Mantle Cell Lymphoma MedDRA version: 20.0 Level: HLT Classification code 10026798 Term: Mantle cell lymphomas System Organ Class: 100000004851
Conditions
Sponsors
Acerta Pharma BV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men and women, = 65 years of age. 2. Pathologically confirmed MCL, with documentation of chromosome translocation t(11;14)(q13;q32) and/or overexpression of cyclin D1 in association with other relevant markers (eg, CD5, CD19, CD20, PAX5). 3. MCL requiring treatment and for which no prior systemic anticancer therapies have been received. 4. Presence of radiologically measurable lymphadenopathy and/or extranodal lymphoid malignancy. 5. ECOG performance status of = 2. 6. Men who are sexually active and can beget children must agree to use highly effective forms of contraception during the study and for 6 months after the last dose of bendamustine, or 12 months after the last dose of rituximab, whichever is longest. Highly effective forms of contraception are defined in Section 9.2.2. 7. Men must agree to refrain from sperm donation during the study and for 6 months after the last dose of bendamustine, or 12 months after the last dose of rituximab, whichever is longest. 8. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty. 9. 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). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 546
Exclusion criteria
Exclusion criteria: 1.History of prior malignancy except for the following: a.Malignancy treated with curative intent and with no evidence of active disease present for more than 2 yrs before screening and felt to be at low risk for recurrence by treating physician b.Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled nonmelanomatous skin cancer c.Adequately treated carcinoma in situ without current evidence of disease 2.Subjects for whom the goal of therapy is tumor debulking before stem cell transplant 3.Any history of CNS lymphoma or leptomeningeal disease 4.Uncontrolled AIHA or ITP 5.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 6.Significant cardiovascular disease such as uncontrolled or untreated 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 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 7.ANC 1.5 x ULN; or AST or ALT > 2.5 x ULN 9.Estimated creatinine clearance of 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 11.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 12.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 13.Known history of infection with HIV 14.Ongoing immunosuppressive therapy, including systemic (eg, IV or oral) corticosteroids within 2 weeks before the first dose of study drug. Note: Subjects may use topical or inhaled corticosteroids or low dose steroids (= 20 mg prednisone equivalent/day for = 2 weeks) as a therapy for comorbid conditions. During study participation, subjects may also receive systemic (eg, IV or oral) corticosteroids as needed for treatment emergent comorbid conditions 15.Known history of anaphylaxis or hypersensitivity to bendamustine, rituximab, or any of their componen
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of acalabrutinib (ACP-196) in combination with bendamustine and rituximab (BR) compared with placebo in combination with BR based on Independent Review Committee (IRC) assessment of progression-free survival (PFS) per the Lugano Classification for Non Hodgkin Lymphoma (NHL) (Cheson 2014) in subjects with previously untreated mantle cell lymphoma (MCL).;Secondary Objective: To evaluate acalabrutinib (ACP-196) in combination with BR compared with placebo in combination with BR in terms of: • Investigator-assessed PFS per the Lugano Classification for NHL • Investigator-assessed ORR per the Lugano Classification for NHL • IRC-assessed overall response rate (ORR), defined as a subject achieving either a partial response (PR) or complete response (CR) per the Lugano Classification for NHL. • Overall survival (OS) • IRC-assessed duration of response (DOR) per the Lugano Classification for NHL • IRC-assessed time to response (TTR) per the Lugano Classification for NHL • IRC-assessed ORR (CR + PR) per Revised Response Criteria for Malignant Lymphoma (Cheson 2007) • PRO by Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym) scale score • PRO by the EuroQol (EQ-5D-5L) index score • PRO by the EORTC QLQ-C30 score • Medical Ressource utilization (MRU);Primary end point(s): The primary endpoint of the study is PFS as assessed by IRC per the Lugano Classification for NHL. The primary analysis is a comparison of PFS between Arm 1 (acalabrutinib plus BR) and Arm 2 (placebo plus BR).;Timepoint(s) of evaluation of this end point: Response assessments will be based on the Lugano Classification for NHL, which incorporates assessments via PET/CT and CT alone. During treatment, CT scans will be performed for tumor assessments at Week 12 (± 7 days), then every 12 weeks until Week 96 (± 7 days), and then every 24 weeks (± 7 days) thereafter. During treatment, PET/CT scans will be performed at Weeks 12 and 24 (± 7 days), and then only t | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Investigator-assessed PFS per the Lugano Classification for NHL •Investigator-assessed ORR (CR+PR) per the Lugano Classification for NHL •IRC-assessed ORR (CR+PR) per the Lugano Classification for NHL •OS •IRC-assessed DOR per the Lugano Classification for NHL •IRC assessed TTR per the Lugano Classification for NHL •IRC-assessed ORR (CR + PR) per Revised Response Criteria for Malignant Lymphoma (Cheson 2007) •PRO as measured by change in scores from baseline to each assessment using the FACT-Lym scale •PRO as measured by change in scores from baseline to each assessment using the EQ-5D-5L index score •PRO by change in scores from baseline to each assessment using the EORTC QLQ-C30 score •MRU associated with the study treatment, including the number of hospitalizations, emergency department visits, blood product transfusions, and use of hematopoietic growth factors, that occur after initiation of study drug.;Timepoint(s) of evaluation of this end point: Response assessments will be based on the Lugano Classification for NHL, which incorporates assessments via PET/CT and CT alone. During treatment: CT scans will be performed for tumor assessments at Week 12 (± 7 days), then every 12 weeks until Week 96 (± 7 days), and then every 24 weeks (± 7 days) thereafter. PET/CT scans will be performed at Weeks 12 and 24 (± 7 days), and then only to confirm CR thereafter. Subjects with confirmed CR are not required to undergo further PET/CT scans on study unless there is suspicion of disease progression PRO assessment will be performed at screening, on Day 1 of Cycles 3, 5, and 8, then every 4 cycles until discontinuation of study treatment, and then every 12 weeks thereafter until disease progression or use of alternative anticancer therapy. | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, Czechia, Czech Republic, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Republic of, Mexico, New Zealand, Peru, Poland, Romania, Russian Federation, Spain, Taiwan, Ukraine, United States, Viet Nam
Contacts
Public ContactACE-LY-308 Clinical Team
Acerta Pharma BV
Outcome results
None listed