Ibrutinib in Treating Patients With Relapsed or Refractory Classical Hodgkin Lymphoma

Inclusion Criteria * Patients with relapsed or refractory classical HL who have previously received autologous stem cell transplant and/or allogeneic stem cell transplant. Patients must have received prior autologous stem cell transplant at least 12 weeks (3 months) before the first dose of ibrutinib and/or allogeneic stem cell transplant must have been completed at least 6 months prior to the first dose of Ibrutinib. OR * Patients with relapsed or refractory HL who have failed at least 2 lines of prior therapy and are not eligible for autologous stem cell transplant due to: * Inability to achieve a CR or PR prior to transplant * Age or comorbid conditions * Inability to collect stem cells * Completion of any prior treatment with radiation, chemotherapy, biologics, and/or other investigational agents at least 4 weeks prior to the first dose of ibrutinib. Patients must have completed any prior immunotherapy (e.g., rituximab or PD-1 inhibition) or antibody drug conjugate therapy (e.g. brentuximab vedotin) at least 4 weeks prior to the first dose of ibrutinib in the absence of clear disease progression. * Prior treatment with at least 2 lines of therapy for HL including brentuximab vedotin. In those patients who cannot receive brentuximab vedotin, treatment with 2 prior therapeutic regimens is sufficient. * Fluorodeoxyglucose (FDG)-avid disease by PET and measurable disease of at least 1.5 cm in minimum dimension by CT scan with contrast, as assessed by the site radiologist. * Adequate hematologic function independent of transfusion and growth factor support for at least 7 days prior to screening and randomization, with the exception of PEGylated GCSF (pegfilgrastim) and darbopoeitin which require at least 14 days prior to screening and randomization defined as: * Absolute neutrophil count \>750 cells/mm3 (0.75 x 109/L). * Platelet count \>50,000 cells/mm3 (50 x 109/L). * Hemoglobin \>8.0 g/dL. * Adequate hepatic and renal function defined as: * Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 3.0 x upper limit of normal (ULN). * Estimated Creatinine Clearance ≥30 ml/min (Cockcroft-Gault) * Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin) * PT/INR \<1.5 x ULN and PTT (aPTT) \<1.5 x ULN. * Men and women ≥ 18 years of age. * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2. * Female subjects who are of non-reproductive potential (i.e., post-menopausal by history-no menses for ≥1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy). Female subjects of childbearing potential must have a negative serum pregnancy test upon study entry. * Male and female subjects who agree to use highly effective methods of birth control (e.g., condoms, implants, injectables, combined oral contraceptives, some intrauterine devices \[IUDs\], sexual abstinence, or sterilized partner) during the period of therapy and for 90 days after the last dose of study drug * 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 and are willing to participate in the study. Exclusion Criteria: * Prior allogeneic Stem cell transplant within 6 months. * Active GVHD or concurrent treatment with immunosuppressive medications as prophylaxis for GVHD * Previous therapy with BTK inhibition * Known cerebral/meningeal disease * Nodular lymphocyte predominant Hodgkin's Lymphoma subtype * Concurrent therapy with other systemic anti-neoplastic or investigational agents * Patients with a known hypersensitivity to any excipient contained in the drug formulation * History of other malignancies, except: * Malignancy treated with curative intent and with no known active disease present for ≥3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician. * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. * Adequately treated carcinoma in situ without evidence of disease. * Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, etc., or chronic administration \[\>14 days\] of \>20 mg/day of prednisone) within 28 days of the first dose of study drug. * Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug * Recent infection requiring systemic treatment that was completed ≤14 days before the first dose of study drug. * Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version 4), grade ≤1, or to the levels dictated in the inclusion/exclusion criteria with the exception of alopecia. * Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia. * History of stroke or intracranial hemorrhage within 6 months prior to enrollment. * Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus (HCV) or hepatitis B virus (HBV). Subjects who are positive for hepatitis B core antibody or hepatitis B surface antigen must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded. * Any uncontrolled active systemic infection * Major surgery within 4 weeks of first dose of study drug. * Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk. * Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization * Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction. * Concomitant use of warfarin or other Vitamin K antagonists. * Requires treatment with a strong cytochrome P450 (CYP) 3A4/5 inhibitor * Currently active, clinically significant hepatic impairment Child-Pugh class B or C according to the Child Pugh classification * Lactating or pregnant * Unwilling or unable to participate in all required study evaluations and procedures. * Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations). Potential subjects must be willing and able to adhere to the following prohibitions and restrictions during the course of the study to be eligible for participation. During the study, subjects should avoid consuming food and beverages containing grapefruit or Seville oranges as these contain certain ingredients that inhibit CYP3A4/5 enzymes.