Clofarabine Plus Cytarabine Compared With Cytarabine Alone in Older Patients With Relapsed or Refractory Acute Myelogenous Leukemia: Results From the CLASSIC I Trial

Stefan Faderl(The University of Texas MD Anderson Cancer Center), Meir Wetzler(The University of Texas MD Anderson Cancer Center), David A. Rizzieri(The University of Texas MD Anderson Cancer Center), Gary J. Schiller(The University of Texas MD Anderson Cancer Center), Madan Jagasia(The University of Texas MD Anderson Cancer Center), Robert K. Stuart(The University of Texas MD Anderson Cancer Center), Siddhartha Ganguly(The University of Texas MD Anderson Cancer Center), David Avigan(The University of Texas MD Anderson Cancer Center), Michael Craig(The University of Texas MD Anderson Cancer Center), Robert H. Collins(The University of Texas MD Anderson Cancer Center), Michael B. Maris(The University of Texas MD Anderson Cancer Center), Tibor Kovacsovics(The University of Texas MD Anderson Cancer Center), Stuart L. Goldberg(The University of Texas MD Anderson Cancer Center), Karen Seiter(The University of Texas MD Anderson Cancer Center), Parameswaran Hari(The University of Texas MD Anderson Cancer Center), Jochen Greiner(The University of Texas MD Anderson Cancer Center), Norbert Vey(The University of Texas MD Anderson Cancer Center), Christian Récher(The University of Texas MD Anderson Cancer Center), Farhad Ravandi(The University of Texas MD Anderson Cancer Center), Eunice S. Wang(The University of Texas MD Anderson Cancer Center), Michael J. Vasconcelles(The University of Texas MD Anderson Cancer Center), Dirk Huebner(The University of Texas MD Anderson Cancer Center), Hagop M. Kantarjian(The University of Texas MD Anderson Cancer Center)
Journal of Clinical Oncology
May 15, 2012
10.1200/jco.2011.37.9743
Cited by 176Open Access
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Abstract

PURPOSE: To compare the receipt of clofarabine plus cytarabine (Clo+Ara-C arm) with cytarabine (Ara-C arm) in patients ≥ 55 years old with refractory or relapsed acute myelogenous leukemia (AML). PATIENTS AND METHODS: Patients were randomly assigned to receive either clofarabine (Clo) 40 mg/m(2) or a placebo followed by Ara-C 1 g/m(2) for five consecutive days. The primary end point was overall survival (OS). Secondary end points included event-free survival (EFS), 4-month EFS, overall remission rate (ORR; complete remission [CR] plus CR with incomplete peripheral blood count recovery), disease-free survival (DFS), duration of remission (DOR), and safety. RESULTS: Among 320 patients with confirmed AML (median age, 67 years), the median OS was 6.6 months in the Clo+Ara-C arm and 6.3 months in the Ara-C arm (hazard ratio [HR], 1.00; 95% CI, 0.78 to 1.28; P = 1.00). The ORR was 46.9% in the Clo+Ara-C arm (35.2% CR) versus 22.9% in the Ara-C arm (17.8% CR; P < .01). EFS (HR: 0.63; 95% CI, 0.49 to 0.80; P < .01) and 4-month EFS (37.7% v 16.6%; P < .01) favored the Clo+Ara-C arm compared with Ara-C arm, respectively. DFS and DOR were similar in both arms. Overall 30-day mortality was 16% and 5% for CLO+Ara-C and Ara-C arms, respectively. In the Clo+Ara-C and Ara-C arms, the most common grade 3 to 4 toxicities were febrile neutropenia (47% v 35%, respectively), hypokalemia (18% v 11%, respectively), thrombocytopenia (16% v 17%, respectively), pneumonia (14% v 10%, respectively), anemia (13% v 0%, respectively), neutropenia (11% v 9%, respectively), increased AST (11% v 2%, respectively), and increased ALT (10% v 3%, respectively). CONCLUSION: Although the primary end point of OS did not differ between arms, Clo+Ara-C significantly improved response rates and EFS. Study follow-up continues, and the role of clofarabine in the treatment of adult patients with AML continues to be investigated.

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