Outpatient Treatment with Clofarabine in a Phase II Study of Older Adult Patients with Previously Untreated Acute Myelogenous Leukemia (AML).

The CLASSIC II trial previously reported an overall remission rate of 46% (38% complete remission [CR] and 8% CR with incomplete platelet recovery [CRp]), median duration of remission 56 weeks, median disease-free survival 37 weeks, median overall survival 41 weeks, and 30- and 60-day mortality rates 10% and 16%, respectively (JCO 2009; 27:371s, A.7062). Among the patients achieving remission, 75% achieved a CR or CRp after the first induction cycle and 25% after the re-induction cycle. This trial allowed physicians the discretion to treat patients with inpatient (IP) or outpatient (OP) clofarabine (CLO). This report describes the experience with OP CLO treatment.

CLASSIC II was a single arm, Phase II study of patients ≥ 60 years of age with untreated AML with at least one unfavorable baseline prognostic factor (PF): age ≥70 years, ECOG performance status 2, antecedent hematological disorder (AHD), and/or intermediate/unfavorable risk karyotype. CLO was administered days 1-5 at 30 mg/m² IV over 1hour during induction and at 20 mg/m² during re-induction/consolidation for a maximum of 6 cycles. Patients with confirmed AML who received one dose of CLO were eligible for analysis.

112 patients (median age 71 years) received a median of 2 cycles of CLO. Thirty-five (31%) patients received OP CLO for a total of 72 outpatient cycles (Table). This report will focus only on OP CLO in cycles 2-6, since only 2 patients received OP CLO in cycle 1. 66 patients initiated a second cycle of clofarabine (38 as re-induction; 28 as consolidation). 33/66 (50%) patients received at least 1 OP cycle of CLO for a total of 70 OP cycles (57% of all cycles 2-6). 12/33 received at least 2 OP cycles of CLO. Patients received a median of 1 OP cycle (range 1-5). All 70 OP cycles were administered for 5 OP days except for 2 cycles given for 2 OP days followed by 3 IP days (associated with OP toxicities: Grade 3 rash in 1 patient and increasing transaminase levels in 1 patient). For the 70 OP cycles, 42 (60%) cycles did not require any subsequent hospitalization, while 28 (40%) cycles required hospitalization. Baseline patient and disease characteristics and treatment toxicities for patients receiving OP versus IP CLO and the reasons for hospitalization after OP CLO will be presented at the meeting.

Outpatient clofarabine can be safely administered to older patients with previously untreated AML and at least one unfavorable prognostic factor. OP CLO was primarily used for cycles 2-6, including both cycle 2 re-induction and consolidation. 60% of OP CLO cycles never required hospitalization. Proper patient selection, education, and monitoring for adverse events after OP CLO are necessary. OP CLO offers patients a more convenient option for treatment of their AML.

Claxton:Genzyme: Research Funding. Myers:Genzyme: Employment. Erba:Lilly: Research Funding; Antisoma: Research Funding; Wyeth: Research Funding; Cephalon: Honoraria, Research Funding; MGI Pharma: Honoraria; Pharmion: Honoraria; Celgene: Honoraria; BMS: Honoraria; Novartis: Honoraria, Research Funding; Genzyme: Consultancy, Honoraria, Research Funding; Gemin-X: Research Funding; Kanisa: Research Funding. Faderl:Genzyme: Research Funding. Arellano:Genzyme: Research Funding. Lyons:Celgene: Consultancy; Johnson&Johnson: Consultancy, Honoraria, Speakers Bureau; GlaxoSmithKline: Consultancy, Speakers Bureau; Amgen Inc.: Consultancy, Honoraria, Research Funding, Speakers Bureau; Genzyme: Research Funding. Kovacsovics:Genzyme: Research Funding. Gabrilove:Genzyme: Research Funding. Warnock:Genzyme: Employment. Kantarjian:Genzyme: Research Funding.