Table II.
Summary of important studies using clofarabine-containing regimen in the treatment of adult patients with AML and MDS.
| Reference | Phase | Number of patients | Patient characteristics | Median age (years) | Treatment schema | ORR (%) | CR (%) | Remarks |
|---|---|---|---|---|---|---|---|---|
| Faderl et al. (2005) [29] | I/II | 29 | Relapsed AML and high risk MDS | 63 | Ara-C and clofarabine combination | 40 | 24 | Low induction mortality (3%), median OS: 5.5 months |
| Agura et al. (2011) [32] | II | 30 | Relapsed/refractory AML | 67 | Ara-C and clofarabine combination | 53 | 47 | Median DFS: 9.5 months |
| Faderl et al. (2012) [46] | III | 320 | Relapsed/refractory AML >55 years | 67 | Induction with clofarabine + ara-C vs. ara-C | 46.9 vs. 22.9 | 35 vs. 18 | Better CR, EFS and ORR in combination arm, no difference in OS |
| Becker et al. (2011) [34] | I/II | 50 | Relapsed/refractory AML | 53 | Clofarabine and high dose ara-C with G-CSF priming (GCLAC) (induction and consolidation) | 61 | 46 | Response independent of age and cytogenetic risk category |
| Faderl et al. (2008) [31] | III | 70 | Elderly frontline AML or high risk MDS | 71 | Induction and consolidation clofarabine vs. clofarabine + ara-C | 59 (67 vs. 31 favoring combination arm) | 63 vs. 31 favoring combination arm | Median OS: 11.4 vs. 5.8 months favoring combination arm (non-significant) |
| Faderl et al. (2012) [33] | II | 60 | Frontline elderly AML | 70 | Ara-C and clofarabine combination, consolidation alternating with decitabine | 66 | 58 | Median OS: 12.7 months |
| Nazha et al. (2011) [38] | II | 51 | Frontline AML | 49 | Combination of ara-C, clofarabine and idarubicin (induction and consolidation) | 71 | 69 | Low 1-month induction mortality (4%), median OS not reached |
| Amadori et al. (2011) [42] | II | 53 | Relapsed/refractory AML | 69 | Induction with clofarabine and temsirolimus, maintenance temsirolimus | 21 | 8 | >50% in vivo inhibition of S6 ribosomal protein phosphorylation highly correlated with response rate |
| Mathisen et al. (2012) [39] | I/II | 31 | Frontline or relapsed/refractory AML | 56 | Combination of clofarabine, idarubicin and cytarabine (CIA) | 44% for phase I relapsed/refractory patients; phase II CIA: 100% for front-line cohort; 43% for relapsed/refractory | 100% for front-line cohort; 36% for relapsed/refractory CIA cohort | Low early mortality rate |
AML, acute myeloid leukemia; MDS, myelodysplastic syndrome; ORR, overall response rate; CR, complete remission; OS, overall survival; DFS, disease-free survival; EFS, event-free survival.