Inclusion Criteria:
* Be willing and able to provide written informed consent for the trial.
* Be greater than or equal to 18 years of age on day of signing informed consent.
* Have measurable disease based on iwCLL or Lugano criteria.
* Have had at least 1 prior line of standard therapy
* Be willing to provide tissue from a bone marrow biopsy if suspected involvement and/or lymph node at enrollment, as well, as a repeat bone marrow biopsy (if involved at diagnosis) after 3 of therapy and at the time of progression and/ or completion of therapy whichever comes first.
* Have a performance status of 0-1 on the ECOG Performance Scale.
* Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.
Hematological Absolute neutrophil count (ANC) ≥1000 /mcL Platelets ≥50,000 / mcL (if bone marrow involvement ≥30,000 mcL) Hemoglobin ≥8 g/dL
Renal Serum creatinine OR ≤1.5 X upper limit of normal (ULN) OR Measured or calculateda ≥60 mL/min for subject with creatinine levels \> 1.5 X institutional Hepatic ULN creatinine clearance (GFR can also be used in place of creatinine or CrCl)
Hepatic Serum total bilirubin ≤1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN AST (SGOT) and ALT (SGPT) ≤2.5 X ULN Albumin \>2.0 mg/dL
Coagulation International Normalized ≤1.5 X ULN unless subject is receiving anticoagulant therapy as Ratio (INR) or long as PT or PTT is within therapeutic range of intended use Prothrombin Time (PT) of anticoagulants
Activated Partial ≤1.5 X ULN unless subject is receiving anticoagulant therapy as Thromboplastin Time long as PT or PTT is within therapeutic range of intended use (aPTT) of anticoagulants
aCreatinine clearance should be calculated per institutional standard.
* Female subject of childbearing potential should have a negative urine or serum pregnancy prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
* Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.
* Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
Exclusion Criteria:
* Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
* Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
* Has a known history of active TB (Bacillus Tuberculosis)
* Hypersensitivity to pembrolizumab or any of its excipients.
* Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
* Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
i. Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
ii. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
\- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
* Has a history of non-infectious pneumonitis that required steroids or has current pneumonitis.
* Has an active infection requiring systemic therapy.
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
* Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
* Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
* Has received a live vaccine within 30 days of planned start of study therapy.
* Has received prior therapy with a PI3K-inhibitor. (Prior therapy with a PI3K-inhibitor is allowed if it was discontinued for intolerance)
* Is pregnant or breast feeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of treatment.
* Has known active central nervous system (CNS) disease and/or lymphomatous involvement. Subjects with previously treated CNS lymphoma and/or lymphomatous meningitis may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
