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
- Conditions
- Mantle Cell LymphomaMedDRA version: 20.0Level: HLTClassification code 10026798Term: Mantle cell lymphomasSystem Organ Class: 100000004851Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-005220-26-IT
- Lead Sponsor
- ACERTA PHARMA BV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 546
1. Men and women, = 65 years of age.
2. 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 in association with other relevant markers(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 (as defined by Lugano Classification for NHL).
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
.1.History of prior malignancy except: a.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. 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.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. 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 (Friderica’s formula: QT/RR0.33) at screening.7.ANC <1.0x109/L or platelet count<75x109/L; for subjects with disease involvement in the bone marrow, ANC <0.75x109/L or platelet count<50x109/L. Subjects will only be considered eligible if peripheral blood counts can be maintained independent of growth factors or transfusions during the screening period. 8.Total bilirubin>1.5xULN; or AST or ALT>2.5xULN. 9.Estimated creatinine clearance of <50mL/min, formula of Cockcroft and Gault 10.Prothrombin time/INR or aPTT (in the absence of a Lupus anticoagulant) >2.0xULN. r.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. 15.Known history of anaphylaxis or hypersensitivity to bendamustine, rituximab, or any of their components. 16.Serologic status reflecting active hepatitis B or C infection. a.Subjects who are anti-HBc positive and who are surface antigen negative will need to have a negative PCR result before randomization. Those who are HbsAg positive or hepatitis B PCR positive will be excluded. b.Subjects who are hepatitis C antibody positive will need to have a negative PCR result before randomization. Those who are hepatitis C PCR positive will be excluded.17.Received a live virus vaccination within 28 days of first dose of study drug.18.History of stroke or intracranial hemorrhage within 6 months of first dose of study drug.19.History of bleeding diathesis. 20.Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before first dose of study drug.21.Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists within 7 days of first dose of study drug.22.Requires treatment with a strong CYP3A inhibitor/inducer.23.Requires treatment with prot
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method