Study of Ibrutinib (a Bruton's Tyrosine Kinase Inhibitor), Versus Temsirolimus in Patients With Relapsed or Refractory Mantle Cell Lymphoma Who Have Received at Least One Prior Therapy
Condition: Mantle Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, Mantle-Cell
Intervention: Ibrutinib; Temsirolimus
Intervention description: 560 mg once daily continuous (without interruption) by mouth for 21-day cycles; 175 mg once daily intravenous infusion on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each 21-day cycle
Intervention MeSH terms: Sirolimus; Temsirolimus; MTOR Inhibitors
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 280.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Mantle cell lymphoma; Relapsed mantle cell lymphoma; Refractory mantle cell lymphoma; Ibrutinib; Bruton's tyrosine kinase inhibitor; Temsirolimus

Summary:

      The purpose of this study is to evaluate the efficacy and safety of ibrutinib versus
      temsirolimus in patients with relapsed or refractory mantle cell lymphoma who received at
      least 1 prior chemotherapy regimen.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Confirmed diagnosis of mantle cell lymphoma (MCL)

          -  Received at least 1 prior rituximab-containing chemotherapy regimen (separate lines of
             therapy are defined as single or combination therapies that are either separated by
             disease progression or by a > 6 month treatment-free interval)

          -  Documented relapse or disease progression following the last anti-MCL treatment

          -  At least 1 measurable site of disease according to Revised Response Criteria for
             Malignant Lymphoma

          -  Eastern Cooperative Oncology Group performance status grade 0 or 1

          -  Protocol-defined hematology and biochemistry laboratory values

        Exclusion Criteria:

          -  Prior nitrosoureas within 6 weeks, chemotherapy within 3 weeks, therapeutic anticancer
             antibodies within 4 weeks, radio- or toxin-immunoconjugates within 10 weeks, radiation
             therapy or other investigational agents within 3 weeks, or major surgery within 4
             weeks of randomization

          -  Prior treatment with temsirolimus, other mTOR inhibitors, ibrutinib, or other Bruton's
             tyrosine kinase (BTK) inhibitors

          -  Known central nervous system lymphoma

          -  Received an allogeneic or autologous hematopoietic stem cell transplant <=6 months
             from the date of randomization and on immunosuppressive therapy or have evidence of
             active graft versus host disease

          -  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
             randomization, adequately treated non-melanoma skin cancer or lentigo maligna without
             evidence of disease, adequately treated cervical carcinoma in situ without evidence of
             disease

          -  History of stroke or intracranial hemorrhage within 6 months prior to randomization

          -  Requires anticoagulation with warfarin or equivalent vitamin K antagonist

          -  Requires treatment with strong CYP3A inhibitor

          -  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

          -  Known history of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV)
             or active hepatitis B virus (HBV) infection or any uncontrolled active systemic
             infection requiring intravenous antibiotics

          -  Woman who is pregnant or breast-feeding

          -  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