TY - JOUR
T1 - Clofarabine plus cytarabine compared with cytarabine alone in older patients with relapsed or refractory acute myelogenous leukemia
T2 - Results from the CLASSIC I trial
AU - Faderl, Stefan
AU - Wetzler, Meir
AU - Rizzieri, David
AU - Schiller, Gary
AU - Jagasia, Madan
AU - Stuart, Robert
AU - Ganguly, Siddhartha
AU - Avigan, David
AU - Craig, Michael
AU - Collins, Robert
AU - Maris, Michael
AU - Kovacsovics, Tibor
AU - Goldberg, Stuart
AU - Seiter, Karen
AU - Hari, Parameswaran
AU - Greiner, Jochen
AU - Vey, Norbert
AU - Recher, Christian
AU - Ravandi, Farhad
AU - Wang, Eunice S.
AU - Vasconcelles, Michael
AU - Huebner, Dirk
AU - Kantarjian, Hagop M.
PY - 2012/7/10
Y1 - 2012/7/10
N2 - 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.
AB - 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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U2 - 10.1200/JCO.2011.37.9743
DO - 10.1200/JCO.2011.37.9743
M3 - Article
C2 - 22585697
AN - SCOPUS:84864050584
SN - 0732-183X
VL - 30
SP - 2492
EP - 2499
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 20
ER -