Clinical trial · Interventional
AT9283 in Treating Young Patients With Relapsed or Refractory Acute Leukemia
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
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Leukemia | Leukemia | ONTOLOGY_EXACT | 0.90 |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| laboratory biomarker analysis | Other | — | UNRESOLVED |
| multikinase inhibitor AT9283 | Drug | — | UNRESOLVED |
| pharmacological study | Other | — | UNRESOLVED |
Design
Arms and outcomes
Arms (0)
[]Primary outcomes (1)
- measure
- Maximum-tolerated dose and recommended phase II dose of multikinase inhibitor AT9283
Secondary outcomes (5)
- measure
- Adverse events to multikinase inhibitor AT9283 and grading severity according to NCI CTCAE Version 4.02
- measure
- 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
- measure
- Plasma concentration measurement of multikinase inhibitor AT9283
- measure
- 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)
- measure
- Results of established and novel prognostic biomarkers (genetic mutations of JAK 1, 2, 3, FLT3, IKAROS, and BCR/ABL) linking to observed responses
Eligibility
Eligibility (as posted)
- Sex
- All
- Maximum age
- 18 Years
Show eligibility criteria text
DISEASE CHARACTERISTICS:
* 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
PATIENT CHARACTERISTICS:
* 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
PRIOR CONCURRENT THERAPY:
* 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 drugsReferences
Publications (0)
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