DA-EPOCH-Rituximab/Metformin (RM) for Double Hit Lymphoma

Subject admitted to in-patient care for day 1 or each cycle and discharged on day 5. On day 6, subject receives Rituximab in outpatient infusion facility. Metformin is dispensed on day 1 of each cycle and taken as follows: Cycle 1 days 1-7 500 mg daily. Days 8-21, 500 mg twice daily. Cycle 2 through end of treatment, metformin given 850 mg twice daily. Inpatient treatment: DA-EPOCH every 21 days Etoposide (VP-16) 50 mg/m2/d civi d1-4 (continuous infusion) Prednisone 60 mg/m2 BID po d1-5 Vincristine 0.4 mg/m2/d civi d 1-4 (continuous infusion) Doxorubicin (Adriamycin) 10 mg/m2/d civi d1-4 (continuous infusion) Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 min d5 If clinically indicated, patients who are deemed appropriate for central nervous system (CNS) prophylaxis by their treating physician will receive either single agent intrathecal methotrexate (12 mg) or triple therapy (15 mg methotrexate, 30 mg cytarabine, 30 mg hydrocortisone) with each cycle of chemotherapy. Rituximab 375 mg/m2 IV every 21 days on D6-8 post DA-EPOCH (per standard institutional guidelines) DA-dose adjustment paradigm based on twice weekly complete blood count (CBC) (dose adjustment above starting doses apply to Etoposide (VP-16), Doxorubicin (Adriamycin) and Cyclophosphamide (Cytoxan). If nadir absolute neutrophil count(ANC)\>500/microliter (uL), 20% increase in all 3 drugs. If nadir\<500/uL on 1 or 2 measurements, same doses as last cycle. If nadir \<500/uL on at least 3 measurements, or nadir platelet \<25,000/uL on 1 measurement, 20% decrease in Etoposide, Doxorubicin and Cyclophosphamide below last cycle. Filgrastim (Neupogen) 5 mcg/kg sc qd beginning on d6 until ANC\>5,000/uL or Pegfilgrastim (Neulasta) 6 mg sc 24-72 hours post chemotherapy. Restaging with CT scans is done after cycle 4 and: complete remission (CR)/partial remission (PR) - complete 2 more cycles of therapy OR consolidation radiation therapy per treating physician. stable disease (SD)/progressive disease (PD) - salvage therapy off study.