Lenalidomide and Combination Chemotherapy (DA-EPOCH-R) in Treating Patients With MYC-Associated B-Cell Lymphomas

Inclusion Criteria

• •1. B-cell lymphoma with comprehensive immunohistochemistry (IHC) panel establishing lineage (CD20, CD3) and cell of origin (CD10, BCL6 and MUM1) in addition to proliferative/prognostic markers (Ki-67, C-myc and BCL2). DHL will be identified using cytogenetics and/or immunohistochemistry as detailed in section 4.1.2 below.
• •2. To define DHL, patients must have evidence of C-myc \[defined as: Cytogenetic evidence (FISH or karyotype) of C-myc breaks (Increased copy number in itself is not considered positivity for C-myc) OR Positive IHC defined as \>40% of the lymphoma cells staining for C-myc\] PLUS either:
• •1. Breaks in BCL-2 via cytogenetic studies or
• •2. BCL-2 immunopositivity in \>70% of lymphoma cells.
• •3. Patients are allowed to have received radiotherapy before enrollment if radiation was given to alleviate pain and/or neurologic compromise as long as there remains areas of measurable disease present. Further, at the investigator's discretion and for patients who are unstable, one cycle of R-CHOP is allowed prior to enrollment but no more than one cycle. For purposes of this trial, prednisone or other corticosteroids used for non-lymphomatous conditions will be allowed. In addition, a prior/recent short course (\< 2 weeks) of steroids for symptom relief of lymphoma-related symptoms will be allowed.
• •4. AST and ALT \< 3 x upper limit of normal (ULN), and total bilirubin \<1.5 x ULN (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver involvement with NHL or stable chronic liver disease per investigator assessment).
• •5. Patients must have adequate renal function by virtue of GFR \> 50 ml/minute using Cockroft-Gault formula.
• •6. Patients must have adequate bone marrow function (platelets \>100,000 and ANC \>1,200). Patients with bone marrow involvement are allowed at the investigator's discretion regardless of cytopenias.
• •7. ECOG PS 0-2.
• •8. Age ≥ 18 years.
• •9. All study participants must be registered into the mandatory lenalidomide REMS® program, and be willing and able to comply with the requirements of the REMS® program.
• •10. Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the lenalidomide REMS® program. (Please see study schema for further details)
• •11. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).
• •12. Ability to read, understand, and sign a written informed consent approved by each institutional IRB. Alternatively, patients with legal guardians who can read, understand, and sign written informed consent may also enroll.