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. 2010 Sep 23;116(12):2070-7. doi: 10.1182/blood-2009-12-261586. Epub 2010 May 13.


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 as NCT00390793.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Cyclophosphamide / administration & dosage
  • Dasatinib
  • Dexamethasone / administration & dosage
  • Doxorubicin / administration & dosage
  • Female
  • Humans
  • Male
  • Middle Aged
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Pyrimidines / administration & dosage*
  • Pyrimidines / therapeutic use
  • Remission Induction
  • Survival Analysis
  • Thiazoles / administration & dosage*
  • Thiazoles / therapeutic use
  • Vincristine / administration & dosage
  • Young Adult


  • Pyrimidines
  • Thiazoles
  • Vincristine
  • Dexamethasone
  • Doxorubicin
  • Cyclophosphamide
  • Dasatinib

Supplementary concepts

  • CVAD protocol

Associated data