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A Phase I/IIa Open-label Study to Assess the Safety, Tolerability and Preliminary Efficacy of AT9283, a Small Molecule Inhibitor of Aurora Kinases, in Patients With Refractory Hematological Malignancies

Phase 1/Phase 2
18 Years
Not Enrolling
Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia, Myelodysplastic Syndromes, Myelofibrosis

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Trial Information

A Phase I/IIa Open-label Study to Assess the Safety, Tolerability and Preliminary Efficacy of AT9283, a Small Molecule Inhibitor of Aurora Kinases, in Patients With Refractory Hematological Malignancies

Dose escalation study of AT9283 administered to patients with refractory hematological
malignancies. Study objectives include identification of MTD and dose limiting toxicities,
preliminary assessment of efficacy and definition of pharmacokinetic profile

Inclusion Criteria:

1. Provision of signed written informed consent

2. Histological or cytological confirmation of one of the following:

Relapsed or refractory AML or ALL; acute leukaemia in patients who are unsuitable for
or refuse standard therapy

CML in chronic phase, accelerated phase or blast crisis that is resistant or
refractory to standard therapy

High-risk MDS, defined as the presence of:

i)Refractory anemia with excess blasts (RAEB, 5-19% bone marrow blasts)


ii)RAEB in transformation to AML (RAEBT with 20-30% bone marrow blasts)

Advanced MMM defined by the presence of one or more of the following features:

i)Hemoglobin < 10 gm/dL (100 g/L)

ii)Platelet count < 100 x 109/L

iii)White blood cell count < 4 x 109/L

iv)Symptomatic splenomegaly or other disease-related symptoms
inadequately controlled by conventional therapies

3. ECOG performance status 0, 1 or 2

4. Male or female, age 18 years or older

5. Negative pregnancy test or history of surgical sterility or evidence of
post-menopausal status (post-menopausal status is defined as any of the following:
natural menopause with menses >1 year ago; radiation induced oophorectomy with last
menses >1 year ago; chemotherapy induced menopause with 1 year interval since last

Exclusion Criteria:

1. Inadequate liver function as demonstrated by serum bilirubin ≥1.5 times the upper
limits of reference range (ULRR) or alanine aminotransferase (ALT) or aspartate
aminotransferase (AST) or alkaline phosphatase (ALP) ≥2.5 times the ULRR (or ≥5 times
the ULRR in the presence of liver metastases)

2. Impaired renal function as demonstrated either by an isolated creatinine value of
≥1.5 times the ULRR OR creatinine clearance < 50 mL/min determined by Cockcroft-Gault
formula. Note there is no requirement to determine a formal creatinine clearance if
the patient's serum creatinine value is ≥1.5 times the ULRR.

3. Radiotherapy or chemotherapy within the 14 days prior to the first dose of AT9283
being administered (Day 1, dose level 1). Planned use of hydroxyurea other than as is
permitted as described in section 11.9.

4. Receiving an investigational anti-cancer treatment concurrently or within 14 days
prior to the start of AT9283 infusion (Day 1)

5. Unresolved CTCAE grade 2 or greater toxicity (other than stable toxicity) from
previous anti-cancer therapy excluding alopecia

6. Any evidence of severe or uncontrolled systemic conditions (e.g., severe hepatic
impairment) or current unstable or uncompensated respiratory or cardiac conditions
which makes it undesirable for the patient to participate in the study or which could
jeopardize compliance with the protocol

7. Active, uncontrolled central nervous system disease

8. Ischemic heart disease or myocardial infarction or unstable cardiac disease within 3
months of study entry

9. Prior infection with human immunodeficiency virus (HIV), hepatitis B or C viruses -
screening for viral infections is not required for entry to this study

10. Major surgery within 28 days prior to the start of AT9283 infusion (Day 1) -
excluding skin biopsies and procedures for insertion of central venous access devices

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety and tolerability

Outcome Time Frame:

Up to 30 days after completing therapy with AT9283

Safety Issue:


Principal Investigator

Hagop Kantarjian, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

The University of Texas M. D. Anderson Cancer Center (MDACC)


United States: Food and Drug Administration

Study ID:




Start Date:

September 2006

Completion Date:

April 2009

Related Keywords:

  • Acute Myeloid Leukemia
  • Acute Lymphoblastic Leukemia
  • Chronic Myeloid Leukemia
  • Myelodysplastic Syndromes
  • Myelofibrosis
  • Primary Myelofibrosis
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Myelodysplastic Syndromes
  • Preleukemia



University of Alabama at Birmingham Birmingham, Alabama  35294-3300
The University of Texas, MD Anderson Cancer Center Houston, Texas  77030