TGR-1202 and Ibrutinib in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Inclusion Criteria

• Histologically confirmed diffuse large B-cell lymphoma (DLBCL) or transformed DLBCL
• Hematoxylin and eosin (H&E) stain and immunohistochemistry (IHC) slides or a representative formalin-fixed, paraffin-embedded (FFPE) tissue block along with the pathology report from initial diagnosis, (as well as, an optional 8 unstained slides of 4 micron thickness to store for future IHC and DNA specified research use), should be sent to be reviewed, and the diagnosis confirmed by University of Nebraska Medical Center (UNMC) (retrospective diagnostic review: treatment may commence prior to the UNMC review); please NOTE: the diagnostic H&E slide and IHC slides will be returned after review; only the optional 8 unstained slides will be retained and stored for future unspecified research use
• Patients with relapsed or refractory DLBCL that has relapsed post-transplant or that has been determined to be ineligible or unsuitable for transplant; patients must have to have received at least one prior systemic therapy
• Patients must have measurable (>= 1.5 cm) or evaluable disease; baseline measurements and evaluations must be obtained within 6 weeks of registration to the study; abnormal PET scans will not constitute evaluable disease, unless verified by CT scan or other appropriate imaging; measurable disease must have at least one objective measurable disease parameter; a clearly defined, bi-dimensionally measurable defect or mass measuring at least 1.5 cm in diameter on a CT scan will constitute measurable disease; proof of lymphoma in the liver is required by a confirmation biopsy; skin lesions can be used as measurable disease provided bi-dimensional measurements are possible
• Absolute neutrophil count (ANC) >= 1.0 x 10^9/L
• By automated or manual review, whichever is greatest
• Platelets >= 100 x 10^9/L:
• Unless due to bone marrow infiltration then eligible if platelets > 50 x 10^9/L)
• Total bilirubin = = 50 mL/min (as calculated by the Cockcroft-Gault method)
• Eastern Cooperative Oncology Group (ECOG) performance status = 2 months
• Ability to swallow and retain oral medication
• Women must not be pregnant or breast-feeding
• All female patients of child-bearing potential must have a negative serum pregnancy test within 2 weeks prior to treatment to rule out pregnancy
• Pregnancy testing is not required for post-menopausal or surgically sterilized women
• Male and female patients of reproductive potential must agree to follow accepted birth control measures throughout the study period and for 30 days after the last dose of either study drug for females and 3 months after the last dose of study drug for males
• Patient must be able to adhere to the study visit schedule and other protocol requirements
• Patient must be aware of the neoplastic nature of his/her disease and willingly sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study
• No serious disease or condition that, in the opinion of the investigator, would compromise the patient's ability to participate in the study

Exclusion Criteria

• Currently receiving cancer therapy (i.e., chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, and surgery and/or tumor embolization) or any investigational drug within 7 days of cycle 1/day 1, 14 days of cycle 1/day 1 for limited palliative radiation, and/or five half-live of an oral therapy
• Corticosteroid therapy started at least 7 days prior to initiation of treatment (prednisone = 470 msec (unless related to pacemaker) on echocardiogram (EKG) within 7 days of initiation of treatment
• Angina not well-controlled by medication
• Poorly controlled or clinically significant atherosclerotic vascular disease including cerebrovascular accident (CVA), transient ischemic attack (TIA), angioplasty, cardi