BACKGROUND: Currently, no standard therapy exists for patients with relapsed and/or refractory non-Hodgkin lymphoma (NHL) who are ineligible for transplantation or who have failed after bone marrow transplantation. The authors of this report investigated the safety and efficacy of clofarabine (CLO) in these patients. METHODS: In a 2-step, open-label study, CLO (as a 1-hour intravenous infusion given daily for 5 days) was given every 28 days (maximum, 6 cycles). In the phase 1 portion (n = 7; standard 3 + 3 study design), the dose was escalated by 2 mg/m(2) to determine the maximum tolerated dose (MTD). The phase 2 study (n = 26) was initiated at the MTD, and patients were followed until disease progression. RESULTS: Of 33 patients who were enrolled, 31 patients (median age, 69 years) were evaluable; 24% failed after previous stem cell transplantation, and 72% were rituximab-refractory. The MTD for CLO was 4 mg/m(2) . The overall response rate was 42%. Seven patients (23%) achieved a complete response, and 6 patients (19%) achieved a partial response. The median response duration was 5 months. Among the rituximab-refractory patients, the overall response rate was 47% (complete response rate, 28%), and the median response duration was 7 months. At a median follow-up of 14 months, 45% of patients remained alive (median overall survival, 10 months). Toxicity was mainly hematologic (≥60% of patients had neutropenia or thrombocytopenia). Nonhematologic toxicity included tumor lysis syndrome, infection, and renal insufficiency (in 6% of patients each). No treatment-related mortality was observed. CONCLUSIONS: Single-agent CLO was active and was tolerated well in patients with refractory NHL, including patients in a rituximab-refractory subset. Reversible myelosuppression was the major toxicity. Study is registered at www.clinicaltrials.gov (NCT00156013).
BACKGROUND: Currently, no standard therapy exists for patients with relapsed and/or refractory non-Hodgkin lymphoma (NHL) who are ineligible for transplantation or who have failed after bone marrow transplantation. The authors of this report investigated the safety and efficacy of clofarabine (CLO) in these patients. METHODS: In a 2-step, open-label study, CLO (as a 1-hour intravenous infusion given daily for 5 days) was given every 28 days (maximum, 6 cycles). In the phase 1 portion (n = 7; standard 3 + 3 study design), the dose was escalated by 2 mg/m(2) to determine the maximum tolerated dose (MTD). The phase 2 study (n = 26) was initiated at the MTD, and patients were followed until disease progression. RESULTS: Of 33 patients who were enrolled, 31 patients (median age, 69 years) were evaluable; 24% failed after previous stem cell transplantation, and 72% were rituximab-refractory. The MTD for CLO was 4 mg/m(2) . The overall response rate was 42%. Seven patients (23%) achieved a complete response, and 6 patients (19%) achieved a partial response. The median response duration was 5 months. Among the rituximab-refractory patients, the overall response rate was 47% (complete response rate, 28%), and the median response duration was 7 months. At a median follow-up of 14 months, 45% of patients remained alive (median overall survival, 10 months). Toxicity was mainly hematologic (≥60% of patients had neutropenia or thrombocytopenia). Nonhematologic toxicity included tumor lysis syndrome, infection, and renal insufficiency (in 6% of patients each). No treatment-related mortality was observed. CONCLUSIONS: Single-agent CLO was active and was tolerated well in patients with refractory NHL, including patients in a rituximab-refractory subset. Reversible myelosuppression was the major toxicity. Study is registered at www.clinicaltrials.gov (NCT00156013).
Authors: Koen van Besien; Wendy Stock; Elizabeth Rich; Olatoyosi Odenike; Lucy A Godley; Peter H O'Donnell; Justin Kline; Vu Nguyen; Paula Del Cerro; Richard A Larson; Andrew S Artz Journal: Biol Blood Marrow Transplant Date: 2011-11-09 Impact factor: 5.742
Authors: Camille R Petri; Peter H O'Donnell; Hongyuan Cao; Andrew S Artz; Wendy Stock; Amittha Wickrema; Marjie Hard; Koen van Besien Journal: Leuk Lymphoma Date: 2014-05-27
Authors: A-K Zoellner; S Fritsch; D Prevalsek; N Engel; M Hubmann; R Reibke; C T Rieger; J C Hellmuth; M Haas; F Mumm; T Herold; G Ledderose; W Hiddemann; M Dreyling; A Hausmann; J Tischer Journal: Bone Marrow Transplant Date: 2015-02-02 Impact factor: 5.483
Authors: Jeremy S Abramson; Ronald W Takvorian; David C Fisher; Yang Feng; Eric D Jacobsen; Jennifer R Brown; Jeffrey A Barnes; Donna S Neuberg; Ephraim P Hochberg Journal: Leuk Lymphoma Date: 2013-01-30
Authors: Bruce D Cheson; Peter C Trask; John G Gribben; Natalie Dimier; Eva Kimby; Pieternella J Lugtenburg; Catherine Thieblemont; Elisabeth Wassner-Fritsch; Aino Launonen; Laurie H Sehn Journal: Ann Hematol Date: 2016-11-30 Impact factor: 3.673