Durvalumab with or without Lenalidomide in Treating Patients with Relapsed or Refractory Cutaneous or Peripheral T Cell Lymphoma

Inclusion Criteria

• Documented informed consent of the participant and/or legally authorized representative
• Registered into Revlimid Risk Evaluation and Mitigation Strategy (REMS) program
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Fully recovered from acute toxicities (except alopecia) of all prior therapies to Common Terminology Criteria for Adverse Events (CTCAE) =< grade 1
• Relapsed/refractory disease
• Failed >= 2 prior systemic therapies * NOTE: For systemic anaplastic large cell lymphoma (ALCL) prior systemic therapy must also include progression on brentuximab vedotin
• CUTANEOUS T-CELL LYMPHOMA (CTCL) ONLY
• Histologically confirmed mycosis fungoides (MF) or Sezary syndrome (SS); Phase 1: >= stage IIB OR >= stage IB-IIA folliculotropic/transformed MF; Phase 2: >= stage IB * Stage of disease according to TNMB classification * Pathology report must be diagnostic or be consistent with MF/SS criteria * SS is defined as meeting T4 plus B2 criteria; where the biopsy of erythrodermic skin may only reveal suggestive but not diagnostic histopathological features, the diagnosis may be based on either node biopsy or fulfillment of B2 criteria * For MF where the histological diagnosis by light microscopic examination is not confirmed, diagnostic criteria that has been recommended by the International Society of Cutaneous Lymphomas (ISCL) should be used
• Measurable disease per either modified severity weighted assessment tool (mSWAT), Sezary count or Lugano Classification
• Baseline skin biopsy taken within 6 months available for central review submission
• PERIPHERAL T-CELL LYMPHOMA (PTCL) ONLY (Phase I only):
• Histologically confirmed PTCL as defined by World Health Organization (WHO) 2008 criteria
• Measurable and/or evaluable disease per Lugano classification
• Within 14 days prior to planned start of treatment: Absolute neutrophil count (ANC) >= 1000/mm^3
• Within 14 days prior to planned start of treatment: Platelets >= 100,000/mm^3
• Within 14 days prior to planned start of treatment: Total serum bilirubin =< 2.2 mg/dL
• Within 14 days prior to planned start of treatment: Aspartate aminotransferase (AST) =< 2 x upper limit of normal (ULN)
• Within 14 days prior to planned start of treatment: Alanine aminotransferase (ALT) =< 2 x ULN
• Within 14 days prior to planned start of treatment: Creatinine clearance of >= 30 mL/min per the Cockcroft-Gault formula, if < 30 mL/min, confirm with a 24 hour urine test
• Within 14 days prior to planned start of treatment: If not receiving anticoagulants: international normalized ratio (INR) AND prothrombin (PT) =< 1.5 x ULN * If on anticoagulant therapy: PT must be within therapeutic range of intended used of anticoagulants
• Within 14 days prior to planned start of treatment: Female of childbearing potential: negative urine or serum pregnancy test * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Female of child bearing potential: willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 90 days after the last dose of study medication * Childbearing potential defined as not being surgically sterilized or have not been free from menses for > 1 year
• Male: use an adequate method of contraception starting with the first dose of study therapy through 90 days after the last dose of study therapy

Exclusion Criteria

• Immunotherapy with immune checkpoint inhibitors, cell-based therapies, or cancer vaccines
• Lenalidomide, thalidomide or other immunomodulatory drugs (IMiDs)
• Monoclonal antibody within 5 half-lives of the antibody prior to initiating protocol therapy
• Any systemic therapy, including monoclonal antibody within 28 days or 5 half-lives (whichever is shorter) of initiating protocol therapy
• Any skin-directed therapy within 14 days prior to initiating protocol therapy
• Any radiation therapy within 21 days prior to initiating protocol therapy
• Immunosuppressive medication within 14 days prior to the first dose of study treatment; the following are exceptions to this criterion: * Intranasal, inhaled, topical or local steroid injections (e.g., intra-articular injection) and are on stable dose for at least 28 days * Systemic corticosteroids at physiologic doses of < 10 mg/day of prednisone or equivalent
• Live, attenuated vaccine within 30 days prior to the first dose of protocol therapy
• History of pneumonitis (non-infectious) that required steroids or current pneumonitis
• Disease free of prior malignancies for >= 5 years with the exception of: * Currently treated squamous cell and basal cell carcinoma of the skin, or * Carcinoma in situ of the cervix, or * Surgically removed melanoma in situ of the skin (stage 0) with histological confirmed free margins of excision, or * Prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) that has/have been surgically cured, or * Any other malignancy that has/have been curatively treated with surgery and/or localized radiation
• Allergic reaction/hypersensitivity to thalidomide or to the excipients contained in the formulation of durvalumab
• Female only: pregnant or lactating
• Prior stem cell transplantation
• Acute infection requiring systemic treatment
• Known history of human immunodeficiency virus (HIV) infection
• Active hepatitis B or C infection
• Conditions requiring chronic steroid or immunosuppressive treatment that likely need additional steroid or immunosuppressive treatments in addition to the protocol therapy
• Current peripheral neuropathy >= grade 2
• Renal failure requiring hemodialysis or peritoneal dialysis
• Unstable cardiac disease as defined by one of the following: * Cardiac events such as myocardial infarction (MI) within the past 6 months * NYHA (New York Heart Association) heart failure class III-IV * Uncontrolled atrial fibrillation or hypertension
• Major surgery (as defined by the investigator) within the 28 days prior to the first dose of study treatment
• Active or prior documented autoimmune or inflammatory disorders requiring therapy within the past 3 years prior to the start of treatment; the following are exceptions to this criterion: * Vitiligo or alopecia; * Hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement; or * Psoriasis not requiring systemic treatment
• History of primary immunodeficiency
• Incidence of gastrointestinal disease that may significantly alter the absorption of lenalidomide
• Any other condition that would, in the investigator's judgement, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/psychological issues, etc
• In the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)