Study to Assess the Safety of Escalating Doses of AT9283, in Patients With Leukemias

NCT00522990 | Terminated Phase 1

• 2 other identifiers: AT9283/00022006-0177
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical research study is to find the highest tolerable dose of AT9283 that can be given to patients who have ALL, AML, CML, high-risk myelodysplastic syndromes, or myelofibrosis with myeloid metaplasia. Researchers want to perform pharmacokinetic (PK) testing on blood to find out how quickly the study drug leaves the body and how the body breaks down the drug. The safety and effectiveness of this drug will also be studied.

Conditions

Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Chronic Myeloid Leukemia; Myelodysplastic Syndromes; Myelofibrosis

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability

  Up to 30 days after completing therapy with AT9283

Secondary Outcomes (1)

• Pharmacokinetic profile, Safety and tolerability of maximum tolerated dose, efficacy, pharmacodynamic effect, identify dose limiting toxicities

  Within six months of initiating therapy with AT92823

Study Arms (1)

1

EXPERIMENTAL

Refractory Hematological Malignancies

Drug: AT9283

Interventions

AT9283 DRUG

Three weekly intravenous administration of AT9283

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed written informed consent
• 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
• ECOG performance status 0, 1 or 2
• Male or female, age 18 years or older
• 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 menses

You may not qualify if:

• 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)
• 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.
• 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.
• Receiving an investigational anti-cancer treatment concurrently or within 14 days prior to the start of AT9283 infusion (Day 1)
• Unresolved CTCAE grade 2 or greater toxicity (other than stable toxicity) from previous anti-cancer therapy excluding alopecia
• 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
• Active, uncontrolled central nervous system disease
• Ischemic heart disease or myocardial infarction or unstable cardiac disease within 3 months of study entry
• Prior infection with human immunodeficiency virus (HIV), hepatitis B or C viruses - screening for viral infections is not required for entry to this study
• 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

Sponsors & Collaborators

• Astex Pharmaceuticals, Inc.: lead

Study Sites (2)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

The University of Texas, MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Foran J, Ravandi F, Wierda W, Garcia-Manero G, Verstovsek S, Kadia T, Burger J, Yule M, Langford G, Lyons J, Ayrton J, Lock V, Borthakur G, Cortes J, Kantarjian H. A phase I and pharmacodynamic study of AT9283, a small-molecule inhibitor of aurora kinases in patients with relapsed/refractory leukemia or myelofibrosis. Clin Lymphoma Myeloma Leuk. 2014 Jun;14(3):223-30. doi: 10.1016/j.clml.2013.11.001. Epub 2013 Nov 14.

  PMID: 24355079 RESULT

Related Links

• Publication of the Study Results

MeSH Terms

Conditions

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

Interventions

1-cyclopropyl-3-(3-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl)urea

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2007
• First Posted: August 30, 2007
• Study Start: September 1, 2006
• Primary Completion: April 1, 2009
• Study Completion: April 1, 2009
• Last Updated: August 2, 2024

Record last verified: 2024-08

Locations

US (2)