AT9283 in Treating Young Patients With Relapsed or Refractory Acute Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01431664
Recruitment Status : Completed
First Posted : September 9, 2011
Last Update Posted : December 2, 2014
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Leukemia Drug: multikinase inhibitor AT9283 Other: laboratory biomarker analysis Other: pharmacological study Phase 1

Detailed Description:



  • 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Masking: None (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
Study Start Date : September 2011
Actual Primary Completion Date : July 2014
Actual Study Completion Date : July 2014

Primary Outcome Measures :
  1. Maximum-tolerated dose and recommended phase II dose of multikinase inhibitor AT9283

Secondary Outcome Measures :
  1. Adverse events to multikinase inhibitor AT9283 and grading severity according to NCI CTCAE Version 4.02
  2. 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
  3. Plasma concentration measurement of multikinase inhibitor AT9283
  4. 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)
  5. Results of established and novel prognostic biomarkers (genetic mutations of JAK 1, 2, 3, FLT3, IKAROS, and BCR/ABL) linking to observed responses

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed acute leukemia according to the following criteria:

    • Acute lymphoblastic leukemia (ALL) meeting any of the following criteria:

      • Second relapse
      • Refractory to induction therapy for first relapse
      • Third or subsequent relapse
    • Acute myeloid leukemia (AML) meeting any of the following criteria:

      • Second or subsequent relapse
      • Refractory to an induction therapy for first relapse
      • Without a curative treatment option
    • Other type of acute leukemia meeting any of the following criteria:

      • First or subsequent relapse
      • Refractory to induction therapy
      • Not eligible for any therapy of higher curative potential
  • No chronic myeloid leukemia (CML)
  • Patients in relapse must have ≥ 5% blasts in the bone marrow
  • Patients with refractory disease following induction must have ≥ 20% blasts in the bone marrow
  • No evidence of CNS disease


  • Karnofsky performance status (PS) 50-100% OR Lansky PS 50-100%
  • Life expectancy ≥ 8 weeks
  • Serum bilirubin < 1.5 times upper limit of normal (ULN)
  • ALT or AST < 2.5 times ULN (5 times ULN if due to leukemic infiltration of the liver)
  • Creatinine clearance ≥ 60 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile female patients must use 2 of the following combined forms of contraception (oral, injected, or implanted hormonal contraception and condom OR intra-uterine device and condom OR diaphragm with spermicidal gel and condom) before, during, and for 6 months after completion of study therapy
  • Male patients must use 1 form of highly effective contraception (condom plus spermicidal gel) during and for 6 months after completion of study therapy

    • Men with pregnant or lactating partners should be advised to use barrier-method contraception (condom plus spermicidal gel)
  • No serological positivity for hepatitis B, hepatitis C, or HIV
  • No congenital heart disease, with the exception of patent foramen ovale or small muscular ventricular septal deficit (within the first year of life)
  • No uncontrolled arterial hypertension (defined as a systolic blood pressure [BP] and/or diastolic BP ≥ 95th percentile for age and height)
  • No fractional shortening of ≤ 29% on echocardiogram
  • No active graft-vs-host disease
  • No current non-malignant systemic disease considered high medical risk, including any of the following:

    • Active uncontrolled infection
    • Unstable or uncompensated respiratory or cardiac condition that makes study participation undesirable
  • No other condition that, in the Investigator's opinion, would not make the patient a good candidate for the clinical trial


  • Recovered from toxicity of prior therapy, including toxicity following hematopoietic stem cell transplantation

    • Alopecia or certain grade 1 toxicities allowed at the discretion of the Investigator
  • A maximum of 2 days of hydroxycarbamide 10-20 mg/kg/day (or according to local practice) in patients with AML and hyperleukocytosis allowed
  • At least 7 days since prior investigational drugs (except antibodies for which a 4-week window must be observed)
  • At least 7 days since prior protein kinase inhibitors and intrathecal therapy

    • Concurrent intrathecal therapy allowed from course 2 onwards in patients with ALL
  • At least 14 days since prior cytotoxic therapy, including vincristine and other anti-neoplastics
  • No prior major thoracic or abdominal surgery from which the patient has not yet recovered
  • No prior aurora kinase inhibitor
  • No concurrent steroid therapy

    • Multikinase inhibitor AT9283 administration may be commenced once steroids have started; however, steroids may not be started once multikinase inhibitor AT9283 has started
    • Up to 5 days of prior oral dexamethasone (6 mg/m^2) for patients with ALL experiencing a rapid rise in blast count allowed
  • No other concurrent interventional clinical study

    • Participation in an observational study allowed
  • No other concurrent anticancer therapy or investigational drugs

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01431664

United Kingdom
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
Sponsors and Collaborators
Cancer Research UK
Principal Investigator: Josef Vormoor Sir James Spence Institute of Child Health at Royal Victoria Infirmary

Responsible Party: Cancer Research UK Identifier: NCT01431664     History of Changes
Other Study ID Numbers: CDR0000709775
First Posted: September 9, 2011    Key Record Dates
Last Update Posted: December 2, 2014
Last Verified: December 2014

Keywords provided by Cancer Research UK:
recurrent childhood acute lymphoblastic leukemia
recurrent childhood acute myeloid leukemia
acute leukemias of ambiguous lineage
acute undifferentiated leukemia
secondary acute myeloid leukemia

Additional relevant MeSH terms:
Neoplasms by Histologic Type