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)