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Clinical Trial
. 2012 Jul 10;30(20):2492-9.
doi: 10.1200/JCO.2011.37.9743. Epub 2012 May 14.

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  1 , Meir Wetzler, David Rizzieri, Gary Schiller, Madan Jagasia, Robert Stuart, Siddhartha Ganguly, David Avigan, Michael Craig, Robert Collins, Michael Maris, Tibor Kovacsovics, Stuart Goldberg, Karen Seiter, Parameswaran Hari, Jochen Greiner, Norbert Vey, Christian Recher, Farhad Ravandi, Eunice S Wang, Michael Vasconcelles, Dirk Huebner, Hagop M Kantarjian
Affiliations
Clinical Trial

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 et al. J Clin Oncol. .

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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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
CONSORT diagram of patient distribution in the CLASSIC I (Clofarabine and Ara-C Studying Survival via Induction and Consolidation) trial. AE, adverse event; AML, acute myelogenous leukemia; Ara-C, cytarabine; Clo+Ara-C, clofarabine plus cytarabine.
Fig 2.
Fig 2.
Kaplan-Meier curves for (A) overall survival, (B) overall survival by random assignment strata, (C) event-free survival, and (D) event-free survival by random assignment strata. Ara-C, cytarabine; Clo+Ara-C, clofarabine plus cytarabine; HR, hazard ratio; REF, primary refractory disease or first pretrial induction remission duration < 6 months; REL, first pretrial induction remission duration ≥ 6 months.
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