AT9283 in Treating Young Patients With Relapsed or Refractory Acute Leukemia
RATIONALE: AT9283 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I/IIa clinical trial is studying the side effects and best dose of AT9283 in treating young patients with relapsed or refractory acute leukemia.
Drug: multikinase inhibitor AT9283
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Cancer Research UK Phase I/IIa Trial of AT9283 (A Selective Inhibitor of Aurora Kinases) Given Over 72 Hours Every 21 Days Via Intravenous Infusion in Children and Adolescents Aged 6 Months to 18 Years With Relapsed and Refractory Acute Leukemia|
- Maximum-tolerated dose and recommended phase II dose of multikinase inhibitor AT9283
- Adverse events to multikinase inhibitor AT9283 and grading severity according to NCI CTCAE Version 4.02
- Partial remission, complete remission, or complete remission with incomplete bone marrow recovery using disease-specific criteria based on ANC, platelets, and % blasts in the bone marrow
- Plasma concentration measurement of multikinase inhibitor AT9283
- Tertiary outcome(s) - Ex vivo and in vivo measurement of kinase inhibition using Plasma Inhibitory Activity (PIA) assay, phosphorylated STAT5 assay, and skin-punch biopsy (measuring pHH3, p53, PCNA, Ki67 levels)
- Results of established and novel prognostic biomarkers (genetic mutations of JAK 1, 2, 3, FLT3, IKAROS, and BCR/ABL) linking to observed responses
|Study Start Date:||September 2011|
|Study Completion Date:||July 2014|
|Primary Completion Date:||July 2014 (Final data collection date for primary outcome measure)|
- To identify the maximum-tolerated dose and recommended phase IIb dose of multikinase inhibitor AT9283 in pediatric patients with relapsed or refractory acute leukemia.
- To evaluate the safety and tolerability of this drug in these patients.
- To document evidence of efficacy of this drug in these patients.
- To investigate the pharmacokinetic profile of this drug in plasma in these patients.
- To assess target kinase inhibition by multikinase inhibitor AT9283 in these patients.
- To identify potential predictive molecular biomarkers in these patients.
OUTLINE: This is a multicenter study.
Patients receive multikinase inhibitor AT9283 IV continuously over 72 hours. Treatment repeats every 21 days* for 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving benefit of treatment may continue for up to 6 more courses at the discretion of the chief/principal investigator.
NOTE: *Course length may be extended to a maximum 42 days to allow for recovery of blood counts. Intrathecal therapy is permitted from course 2 onwards in patients with ALL.
Blood specimens are collected for pharmacokinetic and pharmacodynamic studies including molecular predictive biomarkers and ex vivo and in vivo measurement of kinase inhibition assessments.
After completion of study treatment, patients are followed up for 42 days or until recovery of blood counts (whichever is the sooner).
Peer Reviewed and Funded or Endorsed by Cancer Research UK.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01431664
|Royal Marsden Hospital|
|Surrey, London, United Kingdom, SM2 5PT|
|Birmingham Children's Hospital|
|Birmingham,, United Kingdom, B4 6NH|
|Leeds General Infirmary|
|Leeds, United Kingdom, LS1 3EX|
|Royal Manchester Children's Hospital|
|Manchester, United Kingdom, M13 9WL|
|Great North Children's Hospital, Royal Victoria Infirmary|
|Newcastle upon Tyne, United Kingdom, NE1 4LP|
|Principal Investigator:||Josef Vormoor||Sir James Spence Institute of Child Health at Royal Victoria Infirmary|