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, 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 & 3 others Michael Vasconcelles, Dirk Huebner, Hagop M. Kantarjian

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)2492-2499
Number of pages8
JournalJournal of Clinical Oncology
Volume30
Issue number20
DOIs
StatePublished - Jul 10 2012

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Cytarabine
Acute Myeloid Leukemia
Disease-Free Survival
clofarabine
Survival
Febrile Neutropenia
Hypokalemia
Neutropenia
Thrombocytopenia

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Clofarabine plus cytarabine compared with cytarabine alone in older patients with relapsed or refractory acute myelogenous leukemia : Results from the CLASSIC I trial. / Faderl, Stefan; Wetzler, Meir; Rizzieri, David; Schiller, Gary; Jagasia, Madan; Stuart, Robert; Ganguly, Siddhartha; Avigan, David; Craig, Michael; Collins, Robert; Maris, Michael; Kovacsovics, Tibor; Goldberg, Stuart; Seiter, Karen; Hari, Parameswaran; Greiner, Jochen; Vey, Norbert; Recher, Christian; Ravandi, Farhad; Wang, Eunice S.; Vasconcelles, Michael; Huebner, Dirk; Kantarjian, Hagop M.

In: Journal of Clinical Oncology, Vol. 30, No. 20, 10.07.2012, p. 2492-2499.

Research output: Contribution to journalArticle

Faderl, S, Wetzler, M, Rizzieri, D, Schiller, G, Jagasia, M, Stuart, R, Ganguly, S, Avigan, D, Craig, M, Collins, R, Maris, M, Kovacsovics, T, Goldberg, S, Seiter, K, Hari, P, Greiner, J, Vey, N, Recher, C, Ravandi, F, Wang, ES, Vasconcelles, M, Huebner, D & Kantarjian, HM 2012, 'Clofarabine plus cytarabine compared with cytarabine alone in older patients with relapsed or refractory acute myelogenous leukemia: Results from the CLASSIC I trial', Journal of Clinical Oncology, vol. 30, no. 20, pp. 2492-2499. https://doi.org/10.1200/JCO.2011.37.9743
Faderl, Stefan ; Wetzler, Meir ; Rizzieri, David ; Schiller, Gary ; Jagasia, Madan ; Stuart, Robert ; Ganguly, Siddhartha ; Avigan, David ; Craig, Michael ; Collins, Robert ; Maris, Michael ; Kovacsovics, Tibor ; Goldberg, Stuart ; Seiter, Karen ; Hari, Parameswaran ; Greiner, Jochen ; Vey, Norbert ; Recher, Christian ; Ravandi, Farhad ; Wang, Eunice S. ; Vasconcelles, Michael ; Huebner, Dirk ; Kantarjian, Hagop M. / Clofarabine plus cytarabine compared with cytarabine alone in older patients with relapsed or refractory acute myelogenous leukemia : Results from the CLASSIC I trial. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 20. pp. 2492-2499.
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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.",
author = "Stefan Faderl and Meir Wetzler and David Rizzieri and Gary Schiller and Madan Jagasia and Robert Stuart and Siddhartha Ganguly and David Avigan and Michael Craig and Robert Collins and Michael Maris and Tibor Kovacsovics and Stuart Goldberg and Karen Seiter and Parameswaran Hari and Jochen Greiner and Norbert Vey and Christian Recher and Farhad Ravandi and Wang, {Eunice S.} and Michael Vasconcelles and Dirk Huebner and Kantarjian, {Hagop M.}",
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month = "7",
day = "10",
doi = "10.1200/JCO.2011.37.9743",
language = "English (US)",
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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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