Combination Chemotherapy & Lenalidomide in Newly Diagnosed Stage II-IV Peripheral T-cell Non-Hodgkin's Lymphoma

Inclusion Criteria:

   - Histologically confirmed new diagnosis of stage II, III and IV peripheral T-cell
   non-Hodgkin's lymphoma not otherwise specified (NOS), anaplastic large cell lymphoma
   (ALK negative) (ALK positive if IPI 3, 4, or 5), angioimmunoblastic T-cell lymphoma,
   enteropathy associated T-cell lymphoma, hepatosplenic gamma delta T-cell lymphoma

   - Pathology material: hematoxylin and eosin (H&E) stain and immunohistochemistry (IHC)
   slides or a representative formalin-fixed paraffin-embedded (FFPE) tissue block along
   with the pathology report from initial diagnosis, should be sent to be reviewed, and
   the diagnosis confirmed by Mayo Clinic department (retrospective diagnostic review:
   treatment may commence prior to the Mayo Clinic review)

   - No prior therapy with the exception of prior radiation therapy and/or prednisone
   alone, at the discretion of the investigator based on current diagnosis and clinical
   condition; this prednisone treatment will not count toward the 6 cycles of treatment
   given in the study

   - Expected survival duration of > 3 months

   - Karnofsky performance status > 70

   - Absolute neutrophil count (ANC) > 1000 cells/mm^3, unless cytopenias due to
   non-Hodgkin lymphoma (NHL) (i.e., bone marrow involvement or splenomegaly)

   - Platelet count > 100,000/uL or > 75,000/uL if bone marrow (BM) involvement or
   splenomegaly

   - Total bilirubin =< 1.5 x upper normal limit, or =< 3 x upper normal limit if
   documented hepatic involvement with lymphoma, or =< 5 x upper normal limit if history
   of Gilbert's disease

   - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper
   normal limit (=< 5 x upper normal limit if documented hepatic involvement with
   lymphoma)

   - Serum creatinine < 2.0 mg/dL or calculated creatinine clearance (CrCl) > 45 mL/min
   (Cockcroft-Gault)

   - Prothrombin time (PT) or international normalized ratio (INR), and partial
   thromboplastin time (PTT) =< 1.5 x upper limit of normal unless patient is receiving
   anticoagulants; if patient is on warfarin therapy, levels should be within therapeutic
   range

   - If currently not on anticoagulation medication, willing and able to take aspirin (81
   or 325 mg) daily; if aspirin is contraindicated, the patient may be considered for the
   study if on therapeutic dose warfarin or low molecular weight heparin; patients unable
   to take any prophylaxis are not eligible

   - Patients with measurable disease; patients with non-measurable but evaluable disease
   may be eligible after discussion with the principal investigator (PI); baseline
   measurements and evaluations must be obtained within 6 weeks of registration to the
   study; abnormal positron emission tomography (PET)/computed tomography (CT) scans will
   not constitute evaluable disease, unless verified by CT scan or other appropriate
   imaging

   - Patients with measurable disease must have at least one objective measurable disease
   parameter; a clearly defined, bi-dimensionally measurable defect or mass measuring at
   least 1.5 cm in diameter on the CT portion of a PET/CT or CT scan or magnetic
   resonance imaging (MRI) (if appropriate) will constitute measurable disease; proof of
   lymphoma in the liver is required by a confirmation biopsy; skin lesions can be used
   as measurable disease provided bi-dimensional measurements are possible

   - All study participants must be registered into the mandatory Revlimid Risk Evaluation
   and Mitigation Strategy (REMS) program, and be willing and able to comply with the
   requirements of the REMS program

   - Women must not be pregnant or breast-feeding

      - Females of reproductive potential must adhere to the scheduled pregnancy testing
      as required in the Revlimid REMS program

      - All females of childbearing potential must have a blood test within 2 weeks prior
      to registration to rule out pregnancy

      - Pregnancy testing is not required for post-menopausal or surgically sterilized
      women

   - Male and female patients of reproductive potential must agree follow accepted birth
   control measures

   - Patient must be able to adhere to the study visit schedule and other protocol
   requirements

   - Patients must be willing to give written informed consent, and sign an institutionally
   approved consent form before performance of any study-related procedure not part of
   normal medical care as noted above; with the exception of 1 cycle of chemotherapy
   based on current diagnosis and clinical condition, with the understanding that consent
   may be withdrawn by the subject at any time without prejudice to future medical care

   - No serious disease or condition that, in the opinion of the investigator, would
   compromise the patient's ability to participate in the study

Exclusion Criteria:

   - Pregnant or breast feeding females

   - Known seropositive for or active viral infection with human immunodeficiency virus
   (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); patients who are
   seropositive ( i.e. hepatitis B core antibody positive; quantitative deoxyribonucleic
   acid [DNA] negative) are eligible with appropriate prophylaxis

   - Major surgery within 2 weeks of study drug administration

   - Prior malignancies within the past 3 years with exception of adequately treated basal
   cell, squamous cell skin cancer, or thyroid cancer; carcinoma in situ of the cervix or
   breast; prostate cancer of Gleason grade 6 or less with stable prostate-specific
   antigen (PSA) levels

   - Patients with a diagnosis of other peripheral T-cell lymphoma (PTCL) histologies other
   than those specified in the inclusion criteria

   - Contraindication to any of the required concomitant drugs or supportive treatments,
   including hypersensitivity to all anticoagulation and antiplatelet options, or
   antiviral drugs

   - Any other clinically significant medical disease or condition laboratory abnormality
   or psychiatric illness that, in the Investigator's opinion, may interfere with
   protocol adherence or a subject's ability to give informed consent

   - Known hypersensitivity to thalidomide or lenalidomide

   - The development of erythema nodosum if characterized by a desquamating rash while
   taking thalidomide, lenalidomide or similar drugs

   - Ejection fraction of < 45% by either multi gated acquisition scan (MUGA) or
   echocardiogram (ECHO)