| Eligibility |
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.
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