
    slow accrual
  
['lymphoma']
['ibrutinib', 'carfilzomib']

        Inclusion Criteria:

          1. Patients must have a confirmed diagnosis of mantle cell lymphoma with positivity in
             tissue biopsy.

          2. Patients must have previously treated relapsed and/or refractory MCL with at least 2
             prior lines of therapy (prior carfilzomib, ibrutinib, bortezomib, anthracycline,
             rituximab or stem cell transplant are acceptable). There is no upper limit for prior
             lines of therapy.

          3. Understand and voluntarily sign an institutional review board (IRB)-approved informed
             consent form.

          4. Age >/= 18 years at the time of signing the informed consent.

          5. Patients must have bi-dimensional measurable disease (Measureable disease by CT scan
             defined as at least 1 lesion that measures =/>1.5 cm in single dimension.) Patient
             with leukemia phase (peripheral blood involvement), non-measurable disease,
             gastrointestinal (GI) MCL, or bone marrow (BM) MCL are also eligible.

          6. Gastrointestinal or bone marrow or spleen only patients are allowable and will be
             analyzed separately.

          7. Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less

          8. Serum bilirubin <1.5 mg/dl and creatinine (Cr) Clearance >/= 30 mL/min, platelet count
             >75,000/mm^3 and absolute neutrophil count (ANC) > 1,500/mm^3, aspartate
             aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine
             aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) < 3 x upper limit of
             normal or < 5 x upper limit of normal if hepatic metastases are present. (Patients who
             have bone marrow infiltration by MCL are eligible if their ANC is >/= 1000/mm^3
             [growth factor not allowed] or their platelet level is >/= 50,000/mm^3).

          9. Willing and able to participate in all study related procedures and therapy including
             swallowing capsules without difficulty.

         10. Females of childbearing potential (FCBP)* must have a negative serum or urine
             pregnancy test and must be willing to use acceptable methods of birth control during
             the study and for 30 days after the last dose of study treatment. * A female of
             childbearing potential is a sexually mature woman who: 1) has not undergone a
             hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal
             for at least 24 consecutive months (i.e., has had menses at any time in the preceding
             24 consecutive months).

         11. Male patients must use an effective barrier method of contraception during the study
             and for 30 days following the last dose of study treatment if sexually active with a
             female of childbearing potential.

        Exclusion Criteria:

          1. Any serious medical condition including but not limited to, uncontrolled hypertension,
             uncontrolled diabetes mellitus, uncontrolled infection, active/symptomatic coronary
             artery disease, chronic obstructive pulmonary disease (COPD), renal failure, active
             hemorrhage, or psychiatric illness that, in the investigators opinion places the
             patient at unacceptable risk and would prevent the subject from signing the informed
             consent form.

          2. Pregnant or breastfeeding females.

          3. Use of any standard/experimental anti-lymphoma drug therapy, including steroids,
             within 3 weeks of initiation of the study or use of any experimental non-drug therapy
             (e.g., donor leukocyte/mononuclear cell infusions) within 56 days of initiation of the
             study drug treatment.

          4. Prior allogeneic stem cell transplant (SCT) within 16 weeks or autologous SCT within 8
             weeks of initiation of therapy. (Patients that require immunosuppressive therapy are
             not eligible within 60 days of therapy.)

          5. Known human immunodeficiency virus (HIV) infection. Patients with active Hepatitis B
             infection (not including patients with prior Hepatitis B vaccination; or positive
             serum Hepatitis B antibody). Hepatitis C infection is allowed as long as there is no
             active disease and is cleared by GI consultation.

          6. All patients with central nervous system lymphoma.

          7. Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to
             enrollment.

          8. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize
             carfilzomib).

          9. Contraindication to any of the required concomitant drugs or supportive treatments or
             intolerance to hydration due to preexisting pulmonary or cardiac impairment including
             pleural effusion requiring thoracentesis or ascites requiring paracentesis.

         10. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or
             resection of the stomach or small bowel or ulcerative colitis, symptomatic
             inflammatory bowel disease, or partial or complete bowel obstruction, or any other
             gastrointestinal condition that could interfere with the absorption and metabolism of
             ibrutinib.

         11. Major surgery within 4 weeks of initiation of therapy.

         12. Requires anticoagulation with warfarin or equivalent vitamin K antagonist.

         13. Requires treatment with strong CYP3A inhibitors.

         14. The patient has a prior or concurrent malignancy that in the opinion of the
             investigator, presents a greater risk to the patient's health and survival, than of
             the MCL, within the subsequent 6 months at the time of consent. Investigator
             discretion is allowed.

         15. Patients with New York Heart Association (NYHA) Class III and IV heart failure,
             myocardial infarction in the preceding 6 months, and significant conduction
             abnormalities, including but not limited to atrial fibrillation, 2nd degree AV block
             type II, 3rd degree block, Torsade de pointe, QT prolongation (QTc > 450 msec, sick
             sinus syndrome, ventricular tachycardia, symptomatic bradycardia (heart rate < 50
             bpm), hypotension, light headedness and syncope. Patients with atrial fibrillation
             will be excluded even if they are rate-controlled. If there are any active cardiac
             issues, cardiology consultation will be obtained for clearance.

         16. Known history of Pulmonary Hypertension

         17. If the left ventricular ejection fraction (LVEF) < 40, patients will be excluded.

         18. Known history of Cardiomyopathy

         19. Acute infection requiring treatment (systemic antibiotics, antivirals, or antifungals)
             within 14 days prior to initiation of study.
      