Final results of a phase 2 trial of clofarabine and low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia

Tapan M. Kadia, Stefan Faderl, Farhad Ravandi, Elias Jabbour, Guillermo Garcia-Manero, Gautam Borthakur, Alessandra Ferrajoli, Marina Konopleva, Jan Burger, Xuelin Huang, Xuemei Wang, Sherry Pierce, Mark Brandt, Jennie Feliu, Jorge Cortes, Hagop Kantarjian

Research output: Contribution to journalArticle

Abstract

BACKGROUND The treatment of older adults with acute myeloid leukemia (AML) using standard intensive chemotherapy has been associated with poor outcomes. Effective, less toxic therapies are needed to achieve and maintain durable remissions. METHODS One hundred eighteen patients with newly diagnosed AML (median age, 68 years; range, 60-81 years) were treated with a regimen of clofarabine and low-dose cytarabine (LDAC) alternating with decitabine (DAC). The induction consisted of intravenous clofarabine at 20 mg/m2 on days 1 to 5 combined with subcutaneous LDAC at 20 mg twice daily on days 1 to 10. Responding patients were then treated with a prolonged consolidation/maintenance regimen consisting of cycles of clofarabine plus LDAC alternating with cycles of DAC. RESULTS The overall response rate was 68%. The complete remission (CR) rate was 60% overall, 71% for patients with a diploid karyotype, and 50% for patients with an adverse karyotype. The median overall survival (OS) was 11.1 months for all patients and 18.5 months for those achieving a CR/complete remission with incomplete platelet recovery (CRp). The median relapse-free survival for patients achieving a CR/CRp was 14.1 months. According to a multivariate analysis, only adverse cytogenetics and a white blood cell count≥10 × 109/L predicted worse OS. The regimen was well tolerated with 4- and 8-week mortality rates of 3% and 7%, respectively. The most common nonhematologic adverse events were nausea, elevated liver enzymes, and rash. CONCLUSIONS The lower intensity, prolonged-therapy program of clofarabine and LDAC alternating with DAC is well tolerated and highly effective in older patients with AML. Cancer 2015;121:2375-2382.

Original languageEnglish (US)
Pages (from-to)2375-2382
Number of pages8
JournalCancer
Volume121
Issue number14
DOIs
StatePublished - Jul 1 2015
Externally publishedYes

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decitabine
Cytarabine
Acute Myeloid Leukemia
Karyotype
Survival
Poisons
clofarabine
Exanthema
Diploidy
Cytogenetics
Nausea
Leukocytes
Therapeutics
Blood Platelets
Multivariate Analysis

Keywords

  • elderly acute myeloid leukemia (AML)
  • low intensity
  • maintenance

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kadia, T. M., Faderl, S., Ravandi, F., Jabbour, E., Garcia-Manero, G., Borthakur, G., ... Kantarjian, H. (2015). Final results of a phase 2 trial of clofarabine and low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia. Cancer, 121(14), 2375-2382. https://doi.org/10.1002/cncr.29367

Final results of a phase 2 trial of clofarabine and low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia. / Kadia, Tapan M.; Faderl, Stefan; Ravandi, Farhad; Jabbour, Elias; Garcia-Manero, Guillermo; Borthakur, Gautam; Ferrajoli, Alessandra; Konopleva, Marina; Burger, Jan; Huang, Xuelin; Wang, Xuemei; Pierce, Sherry; Brandt, Mark; Feliu, Jennie; Cortes, Jorge; Kantarjian, Hagop.

In: Cancer, Vol. 121, No. 14, 01.07.2015, p. 2375-2382.

Research output: Contribution to journalArticle

Kadia, TM, Faderl, S, Ravandi, F, Jabbour, E, Garcia-Manero, G, Borthakur, G, Ferrajoli, A, Konopleva, M, Burger, J, Huang, X, Wang, X, Pierce, S, Brandt, M, Feliu, J, Cortes, J & Kantarjian, H 2015, 'Final results of a phase 2 trial of clofarabine and low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia', Cancer, vol. 121, no. 14, pp. 2375-2382. https://doi.org/10.1002/cncr.29367
Kadia, Tapan M. ; Faderl, Stefan ; Ravandi, Farhad ; Jabbour, Elias ; Garcia-Manero, Guillermo ; Borthakur, Gautam ; Ferrajoli, Alessandra ; Konopleva, Marina ; Burger, Jan ; Huang, Xuelin ; Wang, Xuemei ; Pierce, Sherry ; Brandt, Mark ; Feliu, Jennie ; Cortes, Jorge ; Kantarjian, Hagop. / Final results of a phase 2 trial of clofarabine and low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia. In: Cancer. 2015 ; Vol. 121, No. 14. pp. 2375-2382.
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abstract = "BACKGROUND The treatment of older adults with acute myeloid leukemia (AML) using standard intensive chemotherapy has been associated with poor outcomes. Effective, less toxic therapies are needed to achieve and maintain durable remissions. METHODS One hundred eighteen patients with newly diagnosed AML (median age, 68 years; range, 60-81 years) were treated with a regimen of clofarabine and low-dose cytarabine (LDAC) alternating with decitabine (DAC). The induction consisted of intravenous clofarabine at 20 mg/m2 on days 1 to 5 combined with subcutaneous LDAC at 20 mg twice daily on days 1 to 10. Responding patients were then treated with a prolonged consolidation/maintenance regimen consisting of cycles of clofarabine plus LDAC alternating with cycles of DAC. RESULTS The overall response rate was 68{\%}. The complete remission (CR) rate was 60{\%} overall, 71{\%} for patients with a diploid karyotype, and 50{\%} for patients with an adverse karyotype. The median overall survival (OS) was 11.1 months for all patients and 18.5 months for those achieving a CR/complete remission with incomplete platelet recovery (CRp). The median relapse-free survival for patients achieving a CR/CRp was 14.1 months. According to a multivariate analysis, only adverse cytogenetics and a white blood cell count≥10 × 109/L predicted worse OS. The regimen was well tolerated with 4- and 8-week mortality rates of 3{\%} and 7{\%}, respectively. The most common nonhematologic adverse events were nausea, elevated liver enzymes, and rash. CONCLUSIONS The lower intensity, prolonged-therapy program of clofarabine and LDAC alternating with DAC is well tolerated and highly effective in older patients with AML. Cancer 2015;121:2375-2382.",
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T1 - Final results of a phase 2 trial of clofarabine and low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia

AU - Kadia, Tapan M.

AU - Faderl, Stefan

AU - Ravandi, Farhad

AU - Jabbour, Elias

AU - Garcia-Manero, Guillermo

AU - Borthakur, Gautam

AU - Ferrajoli, Alessandra

AU - Konopleva, Marina

AU - Burger, Jan

AU - Huang, Xuelin

AU - Wang, Xuemei

AU - Pierce, Sherry

AU - Brandt, Mark

AU - Feliu, Jennie

AU - Cortes, Jorge

AU - Kantarjian, Hagop

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N2 - BACKGROUND The treatment of older adults with acute myeloid leukemia (AML) using standard intensive chemotherapy has been associated with poor outcomes. Effective, less toxic therapies are needed to achieve and maintain durable remissions. METHODS One hundred eighteen patients with newly diagnosed AML (median age, 68 years; range, 60-81 years) were treated with a regimen of clofarabine and low-dose cytarabine (LDAC) alternating with decitabine (DAC). The induction consisted of intravenous clofarabine at 20 mg/m2 on days 1 to 5 combined with subcutaneous LDAC at 20 mg twice daily on days 1 to 10. Responding patients were then treated with a prolonged consolidation/maintenance regimen consisting of cycles of clofarabine plus LDAC alternating with cycles of DAC. RESULTS The overall response rate was 68%. The complete remission (CR) rate was 60% overall, 71% for patients with a diploid karyotype, and 50% for patients with an adverse karyotype. The median overall survival (OS) was 11.1 months for all patients and 18.5 months for those achieving a CR/complete remission with incomplete platelet recovery (CRp). The median relapse-free survival for patients achieving a CR/CRp was 14.1 months. According to a multivariate analysis, only adverse cytogenetics and a white blood cell count≥10 × 109/L predicted worse OS. The regimen was well tolerated with 4- and 8-week mortality rates of 3% and 7%, respectively. The most common nonhematologic adverse events were nausea, elevated liver enzymes, and rash. CONCLUSIONS The lower intensity, prolonged-therapy program of clofarabine and LDAC alternating with DAC is well tolerated and highly effective in older patients with AML. Cancer 2015;121:2375-2382.

AB - BACKGROUND The treatment of older adults with acute myeloid leukemia (AML) using standard intensive chemotherapy has been associated with poor outcomes. Effective, less toxic therapies are needed to achieve and maintain durable remissions. METHODS One hundred eighteen patients with newly diagnosed AML (median age, 68 years; range, 60-81 years) were treated with a regimen of clofarabine and low-dose cytarabine (LDAC) alternating with decitabine (DAC). The induction consisted of intravenous clofarabine at 20 mg/m2 on days 1 to 5 combined with subcutaneous LDAC at 20 mg twice daily on days 1 to 10. Responding patients were then treated with a prolonged consolidation/maintenance regimen consisting of cycles of clofarabine plus LDAC alternating with cycles of DAC. RESULTS The overall response rate was 68%. The complete remission (CR) rate was 60% overall, 71% for patients with a diploid karyotype, and 50% for patients with an adverse karyotype. The median overall survival (OS) was 11.1 months for all patients and 18.5 months for those achieving a CR/complete remission with incomplete platelet recovery (CRp). The median relapse-free survival for patients achieving a CR/CRp was 14.1 months. According to a multivariate analysis, only adverse cytogenetics and a white blood cell count≥10 × 109/L predicted worse OS. The regimen was well tolerated with 4- and 8-week mortality rates of 3% and 7%, respectively. The most common nonhematologic adverse events were nausea, elevated liver enzymes, and rash. CONCLUSIONS The lower intensity, prolonged-therapy program of clofarabine and LDAC alternating with DAC is well tolerated and highly effective in older patients with AML. Cancer 2015;121:2375-2382.

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