The combination of oxaliplatin, fludarabine (FLU), cytarabine (Ara-c), and rituximab (R) (OFAR) in patients with Richter's Transformation and FLU-refractory CLL

6608 Background: Patients with (FLU-ref) CLL and Richter’s transformation (RT) have a very poor prognosis. Oxaliplatin (OX), a platinum analog with a 1,2-diaminocyclohexamine carrier ligand, has a different activity and side effect profile from cisplatin. OX covalently binds DNA, inducing DNA intra- and inter-strand cross-links. FLU and Ara-c act synergistically to inhibit excision-repair of DNA cross-links, thereby providing the rationale for combining OX, FLU, Ara-c, and R (OFAR). Methods: The phase I portion of a phase I/II study of the OFAR regimen had increasing doses of OX. The OFAR regimen consists of OX 17.5, 20, or 25mg/m2, d1–4; fludarabine 30mg/m2, d2,3; Ara-c 1gm/m2, d2,3; and rituximab 375mg/m2, d3. Courses were given every 4 wks; patients received Neulasta 6mg each course and prophylaxis for tumor lysis, DNA virus’, and PCP. Results: 19 patients enrolled in phase I; 1 received no treatment, 8 had RT, and 10 had FLU-ref CLL. Patients received OX 17.5mg/m2 (3), 20mg/m2 (8), or 25mg/m2 (7). Pat...