Ibrutinib as Early Therapy in Chronic Lymphocytic Leukemia (CLL)

Prior treatment

• Receipt of any prior therapy for CLL. Patients who have received "early intervention" with INVAC-1 vaccine against hTERT will be eligible provided all of the following exist: i) They had no response to the vaccine treatment (persistent CLL \>1% in bone marrow). ii) ≥3 months have elapsed since the last dose of vaccine. iii) No residual toxicities attributable to the vaccine exist at the time of study enrollment. iv) The patient does not meet IWCLL criteria for requiring treatment.
• Current and concurrent use of strong CYP3A4 inhibitors or inducers
• Any other severe concurrent disease, or history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that, in the investigator's opinion, may place the patient at undue risk to undergo therapy with ibrutinib
• 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
• History of ischemic stroke within 6 months prior to enrollment
• Major surgical procedure with 4 weeks of first dose of study drug; open biopsy, or significant traumatic injury within 7 days prior to enrollment date; anticipation of need for major surgical procedure during the course of the study
• Minor surgical procedures, fine needle aspirations or core biopsies within 3 days prior to enrollment date. Bone marrow aspiration and/or biopsy are allowed
• Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug

Other illness

• Active malignancy requiring systemic therapy, other than CLL, with the exception of: adequately treated in situ carcinoma of the cervix uteri; adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin; previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
• Active and uncontrolled autoimmune hemolytic anemia (AIHA) or autoimmune thrombocytopenia (ITP) requiring daily prednisone dose of \>/=20 mg
• Uncontrolled and active systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)
• Evidence of bleeding diathesis or coagulopathy within 3 months (eg, von Willebrand's disease or hemophilia
• Any history of symptomatic intracranial hemorrhage
• Serious, non-healing wound, ulcer, or bone fracture
• Active, uncontrolled infection
• 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, hepatitis B surface antigen, or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded
• Currently active, clinically significant hepatic impairment Child-Pugh class B or C according to the Child Pugh classification (see Appendix L)

Other

• Richter Transformation
• Systemic anticoagulation with warfarin or other Vitamin K antagonists
• Pregnant or breast-feeding females

• Patients must be age \>/=18 years at the time of informed consent, understand and voluntarily sign an informed consent, and be able to comply with study procedures and follow-up examinations.
• No treatment indication according to IWCLL/NCI-WG (International Working Group in Chronic Lymphocytic Leukemia/National Cancer Institute-Working Group) 2008 criteria
• Estimated time to first treatment of 3 years or less according to MDACC nomogram
• ECOG performance status of 0-2
• Male and female subjects who agree to use both a highly effective method of birth control (eg, implants, injectables, combined oral contraceptives, some intrauterine devices \[IUDs\], complete abstinence , or sterilized partner) and a barrier method (eg., condoms, vaginal ring, sponge, etc) during the period of therapy and for 30 days after the last dose of study drug for females and 90 days for males. OR Female subjects who are of non-reproductive potential (ie, post-menopausal by history - no menses for \>/=1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy)
• Adequate hepatic and renal function as indicated by all of the following: Total bilirubin \</=1.5 x institutional Upper Limit of Normal (ULN) except for patients with bilirubin elevation due to Gilbert's disease or of non-hepatic origin who will be allowed to participate, provided bilirubin is \</=3 x institutional ULN; an ALT \</=2.5 x ULN; and estimated creatinine clearance (CrCl) of \> 30 mL/min, as calculated by the Cockcroft- Gault equation.
• PT/INR \<1.5 x ULN and PTT (aPTT) \<1.5 x ULN (unless abnormalities are unrelated to coagulopathy or bleeding disorder).
• Free of prior malignancies for 3 years with exception of patients diagnosed with basal cell or non-metastatic squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast, who are eligible even if they are currently treated or were treated and/or diagnosed in the past 3 years prior to study enrolment
• Diagnosis of CLL/SLL that meets IWCLL diagnostic criteria