BACKGROUND: To improve outcomes of patients with Richter syndrome (RS) and relapsed/refractory chronic lymphocytic leukemia (CLL), we modified the OFAR1 regimen (oxaliplatin and cytarabine doses of the oxaliplatin, fludarabine, cytarabine, and rituximab) for this phase I-II study (OFAR2). PATIENTS AND METHODS: OFAR2 consisted of oxaliplatin at 30 mg/m(2) on days 1 to 4, fludarabine at 30 mg/m(2), cytarabine at 0.5 g/m(2), rituximab at 375 mg/m(2) on day 3, and pegfilgrastim at 6 mg on day 6. Fludarabine and cytarabine were given on days 2 and 3 (cohort 1), days 2 to 4 (cohort 2), or days 2 to 5 (cohort 3) every 4 weeks. Phase II followed the "3 + 3" design of phase I. RESULTS: The 102 patients (CLL, 67; RS, 35) treated had heavily pretreated high-risk disease. Twelve patients were treated in phase I; cohort 2 was the phase II recommended dose. The most common toxicities were hematologic. Response rates (phase II) were 38.7% for RS (complete response [CR], 6.5%) and 50.8% for relapsed/refractory CLL (CR, 4.6%). The median survival durations were 6.6 (RS) and 20.6 (CLL) months. Among 9 patients who underwent allogeneic stem cell transplantation (SCT) as post-remission therapy, none has died (median follow-up, 15.9 months). CONCLUSION: OFAR2 had significant antileukemic activity in RS and relapsed/refractory CLL. Patients undergoing SCT as post-remission therapy had favorable outcomes.
BACKGROUND: To improve outcomes of patients with Richter syndrome (RS) and relapsed/refractory chronic lymphocytic leukemia (CLL), we modified the OFAR1 regimen (oxaliplatin and cytarabine doses of the oxaliplatin, fludarabine, cytarabine, and rituximab) for this phase I-II study (OFAR2). PATIENTS AND METHODS: OFAR2 consisted of oxaliplatin at 30 mg/m(2) on days 1 to 4, fludarabine at 30 mg/m(2), cytarabine at 0.5 g/m(2), rituximab at 375 mg/m(2) on day 3, and pegfilgrastim at 6 mg on day 6. Fludarabine and cytarabine were given on days 2 and 3 (cohort 1), days 2 to 4 (cohort 2), or days 2 to 5 (cohort 3) every 4 weeks. Phase II followed the "3 + 3" design of phase I. RESULTS: The 102 patients (CLL, 67; RS, 35) treated had heavily pretreated high-risk disease. Twelve patients were treated in phase I; cohort 2 was the phase II recommended dose. The most common toxicities were hematologic. Response rates (phase II) were 38.7% for RS (complete response [CR], 6.5%) and 50.8% for relapsed/refractory CLL (CR, 4.6%). The median survival durations were 6.6 (RS) and 20.6 (CLL) months. Among 9 patients who underwent allogeneic stem cell transplantation (SCT) as post-remission therapy, none has died (median follow-up, 15.9 months). CONCLUSION: OFAR2 had significant antileukemic activity in RS and relapsed/refractory CLL. Patients undergoing SCT as post-remission therapy had favorable outcomes.
Authors: B D Cheson; S J Horning; B Coiffier; M A Shipp; R I Fisher; J M Connors; T A Lister; J Vose; A Grillo-López; A Hagenbeek; F Cabanillas; D Klippensten; W Hiddemann; R Castellino; N L Harris; J O Armitage; W Carter; R Hoppe; G P Canellos Journal: J Clin Oncol Date: 1999-04 Impact factor: 44.544
Authors: G Mathé; Y Kidani; M Segiguchi; M Eriguchi; G Fredj; G Peytavin; J L Misset; S Brienza; F de Vassals; E Chenu Journal: Biomed Pharmacother Date: 1989 Impact factor: 6.529
Authors: Apostolia M Tsimberidou; William G Wierda; William Plunkett; Razelle Kurzrock; Susan O'Brien; Sijin Wen; Alessandra Ferrajoli; Farhad Ravandi-Kashani; Guillermo Garcia-Manero; Zeev Estrov; Thomas J Kipps; Jennifer R Brown; Albert Fiorentino; Susan Lerner; Hagop M Kantarjian; Michael J Keating Journal: J Clin Oncol Date: 2008-01-10 Impact factor: 44.544
Authors: M van Gelder; M H van Oers; W G Alemayehu; M C J Abrahamse-Testroote; J J Cornelissen; M E Chamuleau; P Zachée; M Hoogendoorn; M Nijland; E J Petersen; A Beeker; G-J Timmers; L Verdonck; M Westerman; O de Weerdt; A P Kater Journal: Bone Marrow Transplant Date: 2016-02-15 Impact factor: 5.483
Authors: Andrew D Zelenetz; Leo I Gordon; William G Wierda; Jeremy S Abramson; Ranjana H Advani; C Babis Andreadis; Nancy Bartlett; John C Byrd; Myron S Czuczman; Luis E Fayad; Richard I Fisher; Martha J Glenn; Thomas M Habermann; Nancy Lee Harris; Richard T Hoppe; Steven M Horwitz; Christopher R Kelsey; Youn H Kim; Susan Krivacic; Ann S LaCasce; Auayporn Nademanee; Pierluigi Porcu; Oliver Press; Rachel Rabinovitch; Nishitha Reddy; Erin Reid; Ayman A Saad; Lubomir Sokol; Lode J Swinnen; Christina Tsien; Julie M Vose; Lynn Wilson; Joachim Yahalom; Nadeem Zafar; Mary Dwyer; Hema Sundar Journal: J Natl Compr Canc Netw Date: 2015-03 Impact factor: 11.908
Authors: O Al-Sawaf; S Robrecht; J Bahlo; A M Fink; P Cramer; J V Tresckow; E Lange; M Kiehl; M Dreyling; M Ritgen; J Dürig; E Tausch; C Schneider; S Stilgenbauer; C M Wendtner; K Fischer; M Hallek; B Eichhorst Journal: Leukemia Date: 2020-03-17 Impact factor: 11.528