A Phase II Multicenter Single Arm Study to Evaluate the Efficacy and Safety of Single Agent Bruton's Tyrosine Kinase Inhibitor, Ibrutinib, in Patients With Relapsed Refractory Classical Hodgkin's Lymphoma
This phase II trial evaluates how effective 560 mg of ibrutinib taken by mouth daily is in the treatment of classical Hodgkin lymphoma which recurs or does not respond to initial treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth, by altering the environment around the tumor or by affecting the immune system.
• 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.