AT9283 in Treating Young Patients With Relapsed or Refractory Acute Leukemia
- Conditions
- Leukemia
- Registration Number
- NCT01431664
- Lead Sponsor
- Cancer Research UK
- Brief Summary
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.
- Detailed Description
OBJECTIVES:
Primary
* To identify the maximum-tolerated dose and recommended phase IIb dose of multikinase inhibitor AT9283 in pediatric patients with relapsed or refractory acute leukemia.
Secondary
* 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.
Tertiary
* 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 7
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Maximum-tolerated dose and recommended phase II dose of multikinase inhibitor AT9283
- Secondary Outcome Measures
Name Time Method 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) Adverse events to multikinase inhibitor AT9283 and grading severity according to NCI CTCAE Version 4.02 Results of established and novel prognostic biomarkers (genetic mutations of JAK 1, 2, 3, FLT3, IKAROS, and BCR/ABL) linking to observed responses
Trial Locations
- Locations (5)
Royal Marsden Hospital
🇬🇧Surrey, London, United Kingdom
Birmingham Children's Hospital
🇬🇧Birmingham,, United Kingdom
Great North Children's Hospital, Royal Victoria Infirmary
🇬🇧Newcastle upon Tyne, United Kingdom
Leeds General Infirmary
🇬🇧Leeds, United Kingdom
Royal Manchester Children's Hospital
🇬🇧Manchester, United Kingdom