Inclusion Criteria:

• Age ≥ 18 years old.
• Diagnosis of B-CLL, confirmed by flow cytometry and as per the criteria outlined by the IWCLL/Hallek December 2008.
• Patients must have relapse or refractory CLL/SLL who have received at least 1 prior anti-CLL/SLL therapy.
  • Note: There is no upper limit of how many lines of therapy the patient may have received previously.
  • Note:  For the purpose of a particular therapy/regimen to be counted towards the number of prior treatments a patient must have received at least 2 cycles of the regimen; e.g., a patient who change their treatment regimen after only 1 cycle (due to toxicity or any other reason) will not be considered to have "2" prior therapies.
• Cohort 1 only: Exposed to ibrutinib (or other BTK inhibitors and have relapse or refractory disease and require treatment (as outlined in IWCLL/Hallek December 2008). Patients must meet one of the following criteria:
  • They have been previously treated with ibrutinib and were taken off for any reason (except grade 4 toxicity definitely attributed to ibrutinib) as long as deemed safe by the treatment physician to receive ibrutinib again;
  • Currently on ibrutinib and now have progressive disease (ibrutinib refractory);
  • Currently on ibrutinib and have failed to achieve either a complete remission after at least 12 cycles of treatment with ibrutinib or have suboptimal response (< PR) after being on ibrutinib treatment for 6 cycles.
• Patients must have a measurable disease
• ECOG performance status of 0, 1 or 2 at registration.
• The following laboratory values obtained ≤ 14 days prior to registration:
  • Absolute neutrophil count ≥ 1000/mm^3;
  • Platelets ≥ 50,000/mm^3;
  • Serum creatinine ≤ 1.5 x ULN (minimal acceptable creatinine clearance (CLcr) > 25 ml/min);
  • Total bilirubin ≤ 1.5 mg/dL or direct bilirubin ≤ 1.0 mg/dL for patients with Gilbert’s syndrome;
  • SGOT (AST) and SGPT (ALT) ≤ 3 x ULN.
• Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during and after the study. For females, these restrictions apply for 1 month after the last dose of study drug. For males, these restrictions apply for 3 months after the last dose of study drug.
• Negative pregnancy test done ≤ 14 days prior to registration, for persons of childbearing potential only.
  • NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Provide written informed consent.
• Willingness to provide mandatory blood specimens for correlative research.
• Willingness to provide mandatory tissue specimens for correlative research.
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Patient is known to have chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) < 50% of predicted normal.
• Note: FEV1 testing is required for subjects suspected of having chronic obstructive pulmonary disease and subjects must be excluded if FEV1 < 50% of predicted normal.
• Patient is known to have moderate or severe persistent asthma within the past 2 years, or currently has uncontrolled asthma of any classification.
  • Note: subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study.
• Since this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown, any of the following will deem the subject ineligible for the study:
  • Pregnant women;
  • Nursing women;
  • Men or women of childbearing potential who are unwilling to employ adequate contraception.
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.