A Study of the Bruton's Tyrosine Kinase Inhibitor Ibrutinib Given in Combination With Bendamustine and Rituximab in Patients With Newly Diagnosed Mantle Cell Lymphoma
Condition: Mantle Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, Mantle-Cell
Intervention: Bendamustine; Rituximab; Ibrutinib; Placebo
Intervention description: 90 mg/m2 administered intravenously on Days 1-2, Cycles 1-6; 375 mg/m2 administered intravenously on Day 1, Cycles 1-6; if complete response or partial response is achieved, 375 mg/m2 is administered on Day 1 of every second cycle for a maximum of 12 additional doses; 560 mg (4 x 140 mg capsules) administered orally once daily continuously starting on Day 1, Cycle 1 until disease progression, or unacceptable toxicity, or study end; 4 capsules administered orally once daily continuously starting on Day 1, Cycle 1 until disease progression, or unacceptable toxicity, or the final analysis of progression-free survival
Intervention MeSH terms: Rituximab; Bendamustine Hydrochloride
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 523.0
Sex: All
Minimum age: 65 Years
Healthy volunteers: No
Keywords: Mantle cell lymphoma; Ibrutinib; Bruton's tyrosine kinase inhibitor; Bendamustine hydrochloride; Rituximab

Summary:

      The purpose of this study is to evaluate the efficacy and safety of ibrutinib given in
      combination with bendamustine and rituximab in patients 65 years of age or older with newly
      diagnosed mantle cell lymphoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of mantle cell lymphoma (MCL) reviewed and approved by central laboratory:
             diagnosis must include morphology and expression of either cyclin D1 in association
             with other relevant markers (eg, CD19, CD20, PAX5 and CD5) or evidence of t(11;14) as
             assessed by cytogenetics, fluorescent in situ hybridization (FISH), or polymerase
             chain reaction (PCR)

          -  Clinical Stage II, III, or IV by Ann Arbor Classification

          -  At least 1 measurable site of disease according to Revised Response Criteria for
             Malignant Lymphoma

          -  No prior therapies for MCL

          -  Eastern Cooperative Oncology Group (ECOG) performance status grade 0 or 1

          -  Hematology and biochemical laboratory values within protocol-defined limits

          -  Agrees to protocol-defined use of effective contraception

          -  Negative blood or urine pregnancy test at screening

        Exclusion Criteria:

          -  Major surgery within 4 weeks of random assignment

          -  Known central nervous system lymphoma

          -  Diagnosed or treated for malignancy other than MCL, except: malignancy treated with
             curative intent and with no known active disease present for >=3 years before random
             assignment; adequately treated non-melanoma skin cancer or lentigo maligna without
             evidence of disease; adequately treated cervical carcinoma in situ without evidence of
             disease

          -  Patients for whom the goal of therapy is tumor debulking prior to stem cell transplant

          -  History of stroke or intracranial hemorrhage within 6 months prior to random
             assignment

          -  Requires anticoagulation with warfarin or equivalent vitamin K antagonists

          -  Requires treatment with strong CYP3A inhibitors

          -  Clinically significant cardiovascular disease such as uncontrolled or symptomatic
             arrhythmias, congestive heart failure, or myocardial infarction within 6 months of
             Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by
             the New York Heart Association Functional Classification

          -  Vaccinated with live, attenuated vaccines within 4 weeks of random assignment

          -  Known history of human immunodeficiency virus (HIV) or active hepatitis C virus or
             active hepatitis B virus infection or any uncontrolled active systemic infection
             requiring intravenous antibiotics

          -  Any life-threatening illness, medical condition, or organ system dysfunction which, in
             the investigator's opinion, could compromise the patient's safety, interfere with the
             absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue
             risk