What are anti-cancer antibodies

Pembrolizumab alone or with idelalisib or ibrutinib in the treatment of patients with relapsed or refractory chronic lymphocytic leukemia or other low-grade B-cell non-Hodgkin lymphoma

Inclusion criteria:

- CLL / SLL PATIENTS ONLY (ARM A)

- Diagnosis of CLL according to the criteria of the National Cancer Institute (NCI) or SLL according to the criteria of the World Health Organization (WHO); This includes prior documentation of:

- Biopsy-proven small lymphatic lymphoma, or

- Diagnosis of CLL according to NCI working group criteria, as evidenced by all of the following:

- Peripheral blood B-cell count of> 5 x 10 ^ 9 / L consisting of small to medium-sized lymphocytes

- Immunophenotyping in accordance with CLL defined as:

- The predominant population of lymphocytes shares both B-cell antigens (differentiation cluster [CD] 19, CD20 [typically weak expression] or CD23) as well as CD5 in the absence of other pan T-cell markers (CD3, CD2 etc.)

- Clonality, as evidenced by the expression of the kappa or lambda light chain (typically weak immunoglobulin expression) or another genetic method (e.g. immunoglobulin heavy chain variable [IGHV] analysis)

- NOTE: Splenomegaly, hepatomegaly, or lymphadenopathy are not required to diagnose CLL

- Before diagnosing CLL or SLL, mantle cell lymphoma must be excluded by detection of a negative fluorescent in situ hybridization analysis (FISH) for t (11; 14) (immunoglobulin H [IgH] / cyclin D1 [CCND1]) on peripheral Blood or tissue biopsy or negative immunohistochemical stains for cyclin D1 on involved tissue biopsy

- Patients must be treated with at least one previous line of therapy beforehand. EXCEPTION: CLL patients with Richter Transformation or Hodgkin Transformation do not require prior therapy to enroll

- NOTE:

- Prior chemotherapy or biological novel therapy or monoclonal cancer control Antibody-based therapy for the treatment of CLL will be considered in advance therapy; Nutraceutical treatments with no proven benefit in CLL (e.g. as epigallocatechin gallate, or EGCG, found in green tea or other herbal treatments) are not considered "pretreatment"

- Prior oral corticosteroid therapy for an indication other than CLL cannot be considered as "pre-treatment"

- Previous use of corticosteroids in combination with other therapies for The treatment of autoimmune complications in CLL is a prior therapy for CLL

- CLL / SLL patients must have progressive disease with any of the following characteristics based on standard criteria for treatment as defined by the NCI Working Group (WG) 1996

- Symptomatic CLL characterized by any of the following:

- Weight loss> = 10% within the last 6 months

- Extreme tiredness due to CLL

- Fever> = 100.5 degrees Fahrenheit (F) for 2 weeks with no evidence of infection

Soaked night sweats with no signs of infection

- Indications of progressive bone marrow failure with hemoglobin = <11 g / dl or platelet count = <100 x 10 ^ 9 / L.

- Symptomatic or progressive lymphadenopathy, splenomegaly, or hepatomegaly

- Note: pronounced hypogammaglobulinemia or the development of a monoclonal protein in the absence of any of the above criteria for an active disease is not sufficient for protocol therapy or biopsy proven Richter transformation or Hodgkin transformation of CLL; NOTE: both untreated and previously treated patients in this category can be enrolled; You don't have to encounter the progressive disease criteria in the first bullet as long as measurable disease can be detected by positron emission tomography (PET) / computed tomography (CT) or CT (> = 1.5 cm in diameter)

- LOW B-NHL PATIENTS ONLY

- Histologically confirmed relapse (response to last treatment> = 6 months) or refractory (no response to last treatment or duration of response <6 months) sluggish / low-grade B-cell NHL; NOTE: If the patient has previously received Anti-PD-1 or Anti-PDL-1, consult the study chair

- Follicular lymphoma, grades 1, 2 and 3

- Extranodal B-cell lymphoma of the edge zone of the mucosa-associated lymphatic tissue type (MALT)

- Spleen and nodal rim lymphoma

- Lymphoplasmacytic lymphoma including Waldenstrom macroglobulinemia;

- Measurable disease (at least 1 lesion> = 1.5 cm in diameter), such as by CT or the CT images of the PET / CT; NOTE: Patients with Waldenstrom macroglobulinemia are not required to have measurable disease by CT or PET / CT if monoclonal protein is detectable by serum protein electrophoresis and / or immunoglobulin M (IgM) levels are at least 2 times the upper limit of normal

- CLL ONLY WITH RICHTERS TRANSFORMATION (ARM C)

- The CLL diagnosis was confirmed as the biopsy demonstrated Richter's transformation. NOTE: Both untreated and previously treated patients in this category can be admitted for as long as possible. A measurable disease can be detected by PET / CT or CT (> = 1.5 cm in diameter).

- ALL PATIENTS

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

- Creatinine = <1.5 x upper limit of normal (ULN) OR creatinine clearance> = 60 ml / min for subjects with creatinine levels> 1.5 x institutional ULN

- Platelet count> = 25 x 10 ^ 9 / L.

- Absolute neutrophil count> = 0.5 x 10 ^ 9 / L.

- total bilirubin = <1.5 x upper limit of normal value (ULN), unless this is due to Gilbert's disease; If the total bilirubin is> 1.5 x ULN, a direct bilirubin should and must be carried out =

- Aspartate aminotransferase (AST) (serum glutamoxaloacetic acid transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) = <2.5 x ULN

- Negative pregnancy test performed = <7 days prior to registration for women of childbearing potential only

- Submit a written declaration of consent

- Willingness to return to the registering institution for follow-up (during active monitoring phase of the study)

- Note: during the active monitoring phase of a study (i.e. active treatment and observation), participants must be ready to return to the consent institution for follow-up

- Willingness to provide bone marrow, tissue and blood samples for correlative research purposes

Must have failed or unable to tolerate or refuse other available foods and drugs. Administration (FDA) approved effective therapies; NOTE: Patients should not have treatment options other than curative

Exclusion criteria:

- Currently involved in, or participated in, an investigator's study, or using an examining device = <28 days prior to registration

- Receiving systemic steroid therapy or another form of systemic immunosuppressive therapy = <7 days prior to registration; EXCEPTIONS:

- Low doses of steroids (= <20 mg prednisone or an equivalent dose of another steroid / day) for the treatment of non-haematological diseases

- Prior use of corticosteroids is allowed

- After initiation of MK-3475 therapy, steroid can be used to treat potential immune-mediated adverse events (AE) for less than 8 weeks of therapy

- Topical, ocular, intra-articular, intranasal, and inhaled corticosteroids (with minimal systemic absorption) are allowed

- Previous anti-cancer monoclonal antibody = <28 days prior to registration or who did not recover (i.e. =

- Previous chemotherapy or radiation therapy = <14 days prior to registration or who has not recovered (i.e. =

- Note: Patients with =

- Note: If the subject has undergone major surgery, they must have sufficiently recovered from the toxicity and / or complications of the intervention prior to initiating therapy

Known additional malignancy that is progressing or requiring active treatment; EXCEPTIONS (these following exceptions are allowed to sign up for this trial version):

- Basal cell carcinoma or squamous cell carcinoma or melanoma of the skin that has undergone or undergone potentially curative therapy

- In situ cervical cancer that may have been cured or is receiving therapy

- Active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease / syndromes difficult to treat in the past; EXCEPTIONS:

- Patients with vitiligo or resolved asthma / atopy in childhood would be an exception to this rule

- Individuals requiring intermittent use of bronchodilators or local steroid injections would not be excluded from the study

- Patients with hypothyroidism who are stable to hormone replacement, diabetes, or Sjogren's syndrome are eligible for the study

- Patients who have a positive Coombs test but have no evidence of hemolysis are eligible to participate

- Patients with psoriasis who do not require systemic treatment are eligible for participation

- Conditions that are not expected to repeat without an external trigger are: allowed to enroll

- Evidence of interstitial lung disease or active, non-infectious pneumonitis

- Active infection that requires systemic therapy; NOTE: If the infection is controlled, patients are eligible for this study

- Known psychiatric or substance abuse disorders that would interfere with the requirements of the attempt

- One of the following:

- Pregnant woman

- Breastfeeding women

- Men or women of childbearing potential who are unwilling to employ adequate staff Contraception starting with the pre-screening or screening visit for 120 days after the last dose of trial treatment

- Known as HIV positive (Human Immunodeficiency Virus)

Known active hepatitis B (e.g. hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g. hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is recognized); NOTE: Patients with active hepatitis B as defined by the hepatitis B surface antigen positivity or core antibody positivity in the presence of hepatitis B. Deoxyribonucleic acid (DNA) are not eligible for this study; Patients with a positive hepatitis B core antibody but with negative hepatitis B DNA can participate, but hepatitis serologies and hepatitis B DNA must be monitored regularly by the treatment doctor

- NOTE: Intravenous immunoglobulin (IVIG) can cause false positive hepatitis B serology; if patients receiving routine IVIG have a core antibody or core surface antigen positivity with no evidence of active viraemia (hepatitis B negative DNA) you can continue to participate in the study but should have hepatitis serologies and become hepatitis B DNA regularly monitored by the attending physician

- Received a live vaccine = <30 ​​days prior to registration

- New York Heart Association Class III or IV cardiovascular diseases or more recent diseases, myocardial infarction or unstable angina pectoris, or cardiac arrhythmias (<30 days)

- Active central nervous system (CNS) lymphoma or involvement of the cerebrospinal fluid with malignant lymphoma cells that require therapy

- Has clinically significant coagulopathy according to the investigator's judgment

- Received an allogeneic stem cell transplant

- CLL ARMS (ARM A and ARM C) FOR COMBINATION THERAPY, INCLUDING IBRUTINIB or IDELALISIB:

- Chronic use of high cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A) inhibitor or inducer and cannot be switched to an alternative agent for at least 7 days prior to initiation of idelalisib or ibrutinib, which in the opinion of investigators / treating physicians exclude the use of ibrutinib or ibrutinib from idelalisib; Caution should be exercised in patients taking moderate CYP3A inhibitors

- CLL ARMS (ARM A and ARM C) FOR COMBINATION THERAPY, INCLUDING IDELALISIB ARM:

- Chronically takes a sensitive CYP3A substrate or a CYP3A substrate with a narrow therapeutic index and cannot be switched to an alternative agent at least 7 days in advance to study initiation which, in the opinion of the investigator / attending physician, precludes use of idelalisib

- A history of chronic diarrhea, colitis, or bowel perforation that the investigator believes precludes the use of idelalisib.