Tafasitamab and Lenalidomide Followed by Tafasitamab and ICE as Salvage Therapy for Transplant Eligible Patients With Relapsed/ Refractory Large B-Cell Lymphoma

PRIMARY OBJECTIVE: I. Evaluate the anti-tumor activity of tafasitamab and lenalidomide followed by tafasitamab and ICE as first salvage therapy for relapsed/ refractory large B cell lymphoma as assessed by the cumulative complete response rate after completion of 2 or 4 cycles of study treatment. SECONDARY OBJECTIVES: I. Evaluate the overall response rate to tafasitamab and lenalidomide followed by tafasitamab and ICE in transplant eligible patients with relapsed/ refractory large B cell lymphoma after 2-4 total cycles of treatment. II. Evaluate the overall and complete response rate to tafasitamab and lenalidomide after two cycles of treatment in transplant eligible patients with relapsed/ refractory large B cell lymphoma. III. Evaluate the rate of successful stem cell mobilization following study treatment. IV. Evaluate the rate of successful completion of autologous stem cell transplant (ASCT) following study treatment, including patients treated with a total of 2 or 4 cycles of treatment. V. Evaluate the incidence of toxicities according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5. VI. Evaluate the progression free and overall survival in the study population. VII. Compare progression free survival (PFS)/ overall survival (OS) (i.e. long-term outcomes) in patients who proceed to transplant after completing only 2 cycles of tafasitamab/lenalidomide (tafa/len) versus those completing 4 cycles of tafa/len followed by tafa+ICE. EXPLORATORY OBJECTIVES: I. Evaluate the response rate to subsequent anti-CD19 CAR-T treatment in patients who go on to receive further therapy including for relapsed/ refractory disease. II. Assess CD19 expression in patients with subsequent relapse or refractory disease following study treatment by immunohistochemistry. III. Examine the association between clinical outcomes including complete response (CR) rate and pathological tumor characteristics (e.g. in activated B-cell \[ABC\]-type subgroup by gene expression profiling \[GEP\], non-germinal center \[GC\] subtype by Hans, "double/triple hit" phenotype by fluorescence in situ hybridization \[FISH\] and/or GEP). IV. Examine the association between circulating tumor deoxyribonucleic acid (ctDNA) clearance and clinical outcomes including CR rate and PFS. V. Evaluate association between clinical outcomes and duration of response to first-line therapy \< 12 months vs \> 12 months. OUTLINE: Patients receive tafasitamab intravenously (IV), lenalidomide orally (PO), etoposide IV, ifosfamide IV and carboplatin IV on study. Patients undergo positron emission tomography (PET) or computed tomography (CT), and undergo blood sample collection throughout the study. Patients may undergo tissue biopsy on study.