G-CSF priming, clofarabine, and high dose cytarabine (GCLAC) for upfront treatment of acute myeloid leukemia, advanced myelodysplastic syndrome or advanced myeloproliferative neoplasm

Abstract

Prior study of the combination of clofarabine and high dose cytarabine with granulocyte colony-stimulating factor (G-CSF) priming (GCLAC) in relapsed or refractory acute myeloid leukemia resulted in a 46% rate of complete remission despite unfavorable risk cytogenetics. A multivariate analysis demonstrated that the remission rate and survival with GCLAC were superior to FLAG (fludarabine, cytarabine, G-CSF) in the relapsed setting. We therefore initiated a study of the GCLAC regimen in the upfront setting in a multicenter trial. The objectives were to evaluate the rates of complete remission (CR), overall and relapse-free survival (OS and RFS), and toxicity of GCLAC. Clofarabine was administered at 30 mg m(-2) day(-1) × 5 and cytarabine at 2 g m(-2) day(-1) × 5 after G-CSF priming in 50 newly-diagnosed patients ages 18-64 with AML or advanced myelodysplastic syndrome (MDS) or advanced myeloproliferative neoplasm (MPN). Responses were assessed in the different cytogenetic risk groups and in patients with antecedent hematologic disorder. The overall CR rate was 76% (95% confidence interval [CI] 64-88%) and the CR + CRp (CR with incomplete platelet count recovery) was 82% (95% CI 71-93%). The CR rate was 100% for patients with favorable, 84% for those with intermediate, and 62% for those with unfavorable risk cytogenetics. For patients with an antecedent hematologic disorder (AHD), the CR rate was 65%, compared to 85% for those without an AHD. The 60 day mortality was 2%. Thus, front line GCLAC is a well-tolerated, effective induction regimen for AML and advanced myelodysplastic or myeloproliferative disorders.

Trial registration: ClinicalTrials.gov NCT01101880.

© 2014 Wiley Periodicals, Inc.

Figures

Figure 1. Overall and relapse-free survival (RFS)

A. Overall survival. B. Relapse free survival.

Figure 1. Overall and relapse-free survival (RFS)

A. Overall survival. B. Relapse free survival.

Figure 2. Overall survival by presence or absence of minimal residual disease (MRD)

The solid line represents the patients without MRD, the dashed line, the patients with MRD. Note the markedly decreased survival for patients with MRD.

Figure 3. Overall survival after GCLAC for patients with or without antecedent hematologic disorder (AHD)

The solid line represents the survival of patients without AHD (de novo) and the dashed line the survival of patients with AHD.

Figure 4. Overall survival after GCLAC by cytogenetic risk group

The dashed line represents the survival of patients with unfavorable cytogenetics, and the solid line represents the patients with other cytogenetic risk categories (favorable, intermediate and unknown).