Mogamulizumab and Pembrolizumab in Treating Patients With Relapsed or Refractory Diffuse Large B Cell Lymphoma

Inclusion Criteria

• Patients must have histologically confirmed diffuse large B-cell lymphoma; all subtypes of diffuse large B-cell lymphoma are eligible, including high-grade B-cell lymphoma and diffuse large B-cell lymphoma (DLBCL) that has transformed from a prior indolent B-cell non-Hodgkin lymphoma
• Patients must have measurable disease per 2014 Lugano Classification Criteria which is defined as at least one nodal lesion measuring > 1.5 cm in greatest diameter or at least one extranodal lesion measuring > 1.0 cm in greatest diameter
• For phase 2: patients and received at least 2 prior lines of therapy and must have previously received, refused, or been deemed ineligible for autologous stem cell transplantation
• Eastern Cooperative Oncology Group (ECOG) performance status = = 80%)
• Absolute neutrophil count >= 1, 500/mcL (if neutropenia is related to bone marrow involvement with lymphoma, the absolute neutrophil count must be >= 1,000/mcL)
• Platelets >= 75, 000/mcL (if thrombocytopenia is related to bone marrow involvement with lymphoma, the platelet count must be >= 50,000/mcL)
• Hemoglobin >= 9 g/dL (if anemia is related to bone marrow involvement with lymphoma, the hemoglobin must be >= 8 g/dL)
• Total bilirubin = 1.5 x ULN then creatinine clearance >= 40 mL/min/1.73 m^2 as calculated by Cockcroft and Gault equation
• Life expectancy of greater than 3 months
• The effects of MK-3475 (pembrolizumab) in combination with KW-0761 (mogamulizumab) on the developing human fetus are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and 6 months after completion of MK-3475 (pembrolizumab) in combination with KW-0761 (mogamulizumab) administration; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of MK-3475 (pembrolizumab) in combination with KW-0761 (mogamulizumab) administration
• Submit adequate archival tissue specimen (25+ unstained slides or 2 tissue blocks) from a biopsy performed after progression of disease on most recent therapy OR subject is willing to undergo a new core or excisional biopsy to obtain evaluable tumor tissue sample for immunohistochemical assessment and sequencing for B2M loss; repeat samples may be required if adequate tissue is not provided, however, patients may still be considered for enrollment on a case by case basis following consultation with the principal investigator (PI)
• Ability to understand and the willingness to sign a written informed consent document
• Subjects with prior history of chemotherapy-induced or radiation-induced pulmonary toxicity require confirmation of diffuse capacity of the lung for carbon monoxide (DLCO) over 60% (adjusted for hemoglobin) by a pulmonary function test prior to study enrollment

Exclusion Criteria

• Patients who have had previous systemic anti-cancer therapy within 3 weeks of registration or those who have not recovered from adverse events due to agents administered previously
• Note: Patients are considered enrolled on the study after protocol registration and not after signing consent
• Patients who are receiving any other concurrent investigational agents
• Patient is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment; the use of physiologic doses of corticosteroids (e.g. prednisone =< 20 mg/d) may be approved after consultation with the study PI; topical or inhaled corticosteroids are allowed
• Has a known additional malignancy that is progressing or requires active treatment; excepti