Pembrolizumab, Ibrutinib and Rituximab in PCNSL

Inclusion Criteria: * Participant must be able to understand and willing to sign a written informed consent document. * Participant must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care. * Participant must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study. * Participant must be at least 18 years old on day of signing informed consent. * Subjects with pathologically confirmed PCNSL who progressed after CNS-directed therapy, primary refractory disease and relapsed disease are allowed. Participants should have evidence of R/R disease on MRI or CSF cytology. Ocular only recurrences are allowed. * Subjects must have a Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. * Life expectancy of \>3 months (in the opinion of the investigator) * Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 * Must be able to tolerate lumbar puncture and/or Ommaya taps * Demonstrate adequate organ function as defined below, all screening labs should be performed within 28 days of treatment initiation. * Hematology * White Blood Count (WBC) ≥ 2 K/μL * Platelet count ≥ 100 K/μL * Absolute Neutrophil Count ≥ 1.5 K/μL * Hemoglobin \> 9.0 g/dL or ≥ 5.6 mmol/L (Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks) * Biochemistry * Serum creatinine ≤1.5 x institutional ULN OR Measured or calculated creatinine clearance ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN (Creatinine clearance should be calculated per institutional standard) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN(≤5 × ULN for participants with liver metastases) * Total bilirubin (TBILI) ≤ 1.5 x institutional ULN (except subjects with Gilbert Syndrome who must have a total bilirubin level of \< 3.0 x institutional ULN) OR Direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN) * Coagulation studies * INR OR PT and Activated aPTT ≤1.5 × institutional ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants * Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must have a negative serum pregnancy test within 72 hours prior to registration. * Women in the following categories are not considered WOCBP: * Premenarchal * Premenopausal female with 1 of the following: * Documented hysterectomy * Documented bilateral salpingectomy * Documented bilateral oophorectomy * Note: Documentation can come from the site personnel's review of the participant's medical records, medical examination, or medical history interview. * Postmenopausal female: A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. * A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy (HRT). However, in the absence of 12 months of amenorrhea, confirmation with two FSH measurements in the postmenopausal range is required. * Females on HRT and whose menopausal status is in doubt will be required to use one of the non-hormonal highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status before study enrollment. * Women of child-bearing potential (WOCBP; see definition above), must agree to use a highly effective method of contraception consistently and correctly as described below during study treatment and for 120 days after study discontinuation. * 1\. Highly Effective Contraceptive Methods That Are User Dependent a (Failure rate of \< 1% per year when used consistently and correctly.) * a. Combined (estrogen- and progestogen- containing) hormonal contraception b, c * i. Oral * ii. Intravaginal * iii. Transdermal * iv. Injectable * b. Progestogen-only hormonal contraception b, c * i. Oral * ii. Injectable * 2\. Highly Effective Methods That Have Low User Dependency (Failure rate of \<1% per year when used consistently and correctly) * a. Progestogen- only contraceptive implant b, c * b. Intrauterine hormone-releasing system (IUS) b * c. Intrauterine device (IUD) * d. Bilateral tubal occlusion * e. Vasectomized partner: A vasectomized partner is a highly effective contraception method provided that the partner is the sole male sexual partner of the WOCBP and the absence of sperm has been confirmed. If not, an additional highly effective method of contraception should be used. * f. Sexual abstinence: Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatment. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant. * NOTES: Use should be consistent with local regulations regarding the use of contraceptive methods for participants of clinical studies. * Typical use failure rates are lower than perfect-use failure rates (i.e. when used consistently and correctly). * If hormonal contraception efficacy is potentially decreased due to interaction with study treatment, condoms must be used in addition to the hormonal contraception during the treatment period and for at least during study treatment and for 120 day