First report of phase 2 study of dasatinib with hyper-CVAD for the frontline treatment of patients with Philadelphia chromosome-positive (Ph +) acute lymphoblastic leukemia

Farhad Ravandi, Susan O'Brien, Deborah Thomas, Stefan Faderl, Dan Jones, Rebecca Garris, Samuel Dara, Jeffrey Jorgensen, Partow Kebriaei, Richard Champlin, Gautam Borthakur, Jan Burger, Alessandra Ferrajoli, Guillermo Garcia-Manero, William Wierda, Jorge Cortes, Hagop Kantarjian

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216 Scopus citations

Abstract

The combination of cytotoxic chemotherapy and imatinib has improved the outcome for patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Dasatinib has significant clinical activity in patients with imatinib resistance. We examined the efficacy and safety of combining chemotherapy with dasatinib for patients with Ph+ ALL. Newly diagnosed patients received dasatinib 50 mg by mouth twice per day (or 100 mg daily) for the first 14 days of each of 8 cycles of alternating hyper-CVAD, and high-dose cytarabine and methotrexate. Patients in complete remission received maintenance daily dasatinib and monthly vincristine and prednisone for 2 years, followed by dasatinib indefinitely. Thirty-five patients with untreated Ph+ ALL with a median age of 53 years (range, 21-79 years) were treated; 33 patients (94%) achieved complete remission. Two patients died of infections before response assessment. Grade 3 and 4 adverse events included hemorrhage and pleural and pericardial effusions. With a median follow-up of 14 months (range, 4-37 months), the median disease-free survival and median overall survival have not been reached, with an estimated 2-year survival of 64%. The combination of chemotherapy with dasatinib is effective in achieving long-term remissions in patients with newly diagnosed Ph+ ALL. This study was registered at www.ClinicalTrials.gov as NCT00390793.

Original languageEnglish (US)
Pages (from-to)2070-2077
Number of pages8
JournalBlood
Volume116
Issue number12
DOIs
StatePublished - Sep 23 2010
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Ravandi, F., O'Brien, S., Thomas, D., Faderl, S., Jones, D., Garris, R., Dara, S., Jorgensen, J., Kebriaei, P., Champlin, R., Borthakur, G., Burger, J., Ferrajoli, A., Garcia-Manero, G., Wierda, W., Cortes, J., & Kantarjian, H. (2010). First report of phase 2 study of dasatinib with hyper-CVAD for the frontline treatment of patients with Philadelphia chromosome-positive (Ph +) acute lymphoblastic leukemia. Blood, 116(12), 2070-2077. https://doi.org/10.1182/blood-2009-12-261586