Conflict of interest: Nothing to report.
A Phase 2 study of bortezomib combined with either idarubicin/cytarabine or cytarabine/etoposide in children with relapsed, refractory or secondary acute myeloid leukemia: A report from the Children's Oncology Group
Article first published online: 29 JUN 2014
© 2014 Wiley Periodicals, Inc.
Pediatric Blood & Cancer
Volume 61, Issue 10, pages 1754–1760, October 2014
How to Cite
Horton, T. M., Perentesis, J. P., Gamis, A. S., Alonzo, T. A., Gerbing, R. B., Ballard, J., Adlard, K., Howard, D. S., Smith, F. O., Jenkins, G., Kelder, A., Schuurhuis, G. J. and Moscow, J. A. (2014), A Phase 2 study of bortezomib combined with either idarubicin/cytarabine or cytarabine/etoposide in children with relapsed, refractory or secondary acute myeloid leukemia: A report from the Children's Oncology Group. Pediatr. Blood Cancer, 61: 1754–1760. doi: 10.1002/pbc.25117
Clinical Trial information: Identification number: NCT00666588. Trial Registry: clinicaltrials.gov
- Issue published online: 19 AUG 2014
- Article first published online: 29 JUN 2014
- Manuscript Accepted: 5 MAY 2014
- Manuscript Received: 10 MAR 2014
- Takeda/Millenium Pharmaceuticals
- National Cancer Insititute. Grant Numbers: K12CA90433-04, K23CA113337
- NCI Children's Oncology Group. Grant Number: U10CA098543
- pediatric oncology;
This Phase 2 study tested the tolerability and efficacy of bortezomib combined with reinduction chemotherapy for pediatric patients with relapsed, refractory or secondary acute myeloid leukemia (AML). Correlative studies measured putative AML leukemia initiating cells (AML-LIC) before and after treatment.
Patients with <400 mg/m2 prior anthracycline received bortezomib combined with idarubicin (12 mg/m2 days 1–3) and low-dose cytarabine (100 mg/m2 days 1–7) (Arm A). Patients with ≥400 mg/m2 prior anthracycline received bortezomib with etoposide (100 mg/m2 on days 1–5) and high-dose cytarabine (1 g/m2 every 12 hours for 10 doses) (Arm B).
Forty-six patients were treated with 58 bortezomib-containing cycles. The dose finding phase of Arm B established the recommended Phase 2 dose of bortezomib at 1.3 mg/m2 on days 1, 4, and 8 with Arm B chemotherapy. Both arms were closed after failure to meet predetermined efficacy thresholds during the first stage of the two-stage design. The complete response (CR + CRp) rates were 29% for Arm A and 43% for Arm B. Counting additional CRi responses (CR with incomplete neutrophil recovery), the overall CR rates were 57% for Arm A and 48% for Arm B. The 2-year overall survival (OS) was 39 ± 15%. Correlative studies showed that LIC depletion after the first cycle was associated with clinical response.
Bortezomib is tolerable when added to chemotherapy regimens for relapsed pediatric AML, but the regimens did not exceed preset minimum response criteria to allow continued accrual. This study also suggests that AML-LIC depletion has prognostic value. Pediatr Blood Cancer 2014; 61:1754–1760. © 2014 Wiley Periodicals, Inc.