Nivolumab and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma

Inclusion Criteria:

PHASE I: Histologically confirmed B-cell NHL with any of the following subtypes: DLBCL, mantle cell lymphoma (MCL), FL, marginal zone lymphoma (MZL) and lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia (LL/WM), Burkitt's lymphoma (BL); patients with histological transformation to DLBCL from indolent lymphoma, primary mediastinal lymphoma and grey zone lymphoma are eligible
PHASE I: Histologically confirmed classical or lymphocyte predominant Hodgkin's disease that is relapsed or refractory after at least one prior chemotherapy
PHASE I: Patients must have received at least one prior therapy; prior autologous stem cell transplant is permitted; patients with DLBCL who have not had prior high-dose therapy (HDT)/autologous stem cell transplant (ASCT) must be ineligible for transplant; prior lenalidomide is not permitted if patients have progressed on therapy
PHASE IB DOSE EXPANSION: Histologically confirmed classical or lymphocyte predominant Hodgkin's disease
PHASE IB DOSE EXPANSION: Patients must have received at least one prior therapy; prior autologous stem cell transplant is permitted; patients who have not had prior HDT/ASCT must be ineligible for transplant; prior lenalidomide is not permitted if patients have progressed on therapy

PHASE II: Histologically confirmed B-cell NHL:

Cohort 1: with only de novo DLBCL or transformed indolent Non-Hodgkin's lymphoma (excludes Richter's syndrome).
Cohort 2: with only FL of grade 1, 2 or 3a
PHASE II: Patients must have received at least one prior therapy (in patients with transformed DLBCL must have received at least one prior therapy; prior autologous stem cell transplant is permitted; patients with DLBCL who have not had prior HDT/ASCT must be ineligible for transplant; prior lenalidomide is not permitted if patients have progressed on therapy
Be willing and able to provide written informed consent/assent for the trial
Have evaluable disease
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Absolute neutrophil count (ANC) >= 1,500 /mcL
Platelets >= 100,000 /mcL in the absence of transfusion support within 7 days of determining eligibility
Hemoglobin >= 8 g/dL
Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 40 mL/min creatinine clearance
Serum total bilirubin =< 1.5 X ULN OR except subjects with Gilbert syndrome, who can have total bilirubin < 3.0 mg/dL
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 X ULN
Female subject of childbearing potential should have a negative urine or serum pregnancy at screening and within 24 hours 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 should agree to ongoing pregnancy testing during the course of the study and after the end of study therapy; female 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; males must refrain from donating sperm during study participation and for 120 days after the last dose of study medication
Willing and able to receive adequate prophylaxis and/or therapy for thromboembolic events
Be willing and able to understand and give written informed consent and comply with all study related procedures

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 3 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; subjects may use topical or inhaled corticosteroids or low-dose steroids (=< 20 mg of prednisone or equivalent per day) as therapy for comorbid conditions; during study participation, subjects may receive systemic or enteric corticosteroids as needed for treatment-emergent comorbid conditions
Has a known history of active TB (bacillus tuberculosis)
Hypersensitivity to nivolumab or lenalidomide or any of their excipients
Has had a prior anti-cancer monoclonal antibody (mAb) within 2 weeks prior to study day 1 or who 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 or radiation therapy within 2 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

Note: subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study
Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy; patients must be 4 weeks out from major procedures
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 known active central nervous system (CNS) lymphoma
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 (thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment; conditions expected to not recur in the absence of an external trigger
Has an active infection requiring intravenous systemic therapy
Is unable to swallow capsules or malabsorption syndrome, disease or condition significantly affecting gastrointestinal function
Clinically significant cardiovascular disease with uncontrolled arrhythmia, New York Association class 3 or 4 congestive heart failure, history of myocardial infarction within 6 months, or prolonged corrected QT (QTc) > 500 msec
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
Has progressed on prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Has progressed on prior therapy with lenalidomide
Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
Has 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 detected)
Has a history of deep venous thrombosis/embolism, threatening thromboembolism or known thrombophilia or are at a high risk for a thromboembolic event in the opinion of the investigator and who are not willing/able to take venous thromboembolic event prophylaxis during the entire treatment period
Has a history of prior allogeneic hematopoietic cell transplant with a history of prior Graft Versus Host Disease