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

January 8, 2016 updated by: Astex Pharmaceuticals, Inc.

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

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

Study Type

Interventional

Enrollment (Actual)

48

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas, MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

    or

    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 menses

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Refractory Hematological Malignancies
Drug: AT9283
Three weekly intravenous administration of AT9283

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety and tolerability
Time Frame: Up to 30 days after completing therapy with AT9283
Up to 30 days after completing therapy with AT9283

Secondary Outcome Measures

Outcome Measure
Time Frame
Pharmacokinetic profile, Safety and tolerability of maximum tolerated dose, efficacy, pharmacodynamic effect, identify dose limiting toxicities
Time Frame: Within six months of initiating therapy with AT92823
Within six months of initiating therapy with AT92823

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Astex Pharmaceuticals, Inc.

Investigators

  • Principal Investigator: Hagop Kantarjian, MD, The University of Texas M. D. Anderson Cancer Center (MDACC)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2006

Primary Completion (Actual)

April 1, 2009

Study Completion (Actual)

April 1, 2009

Study Registration Dates

First Submitted

August 29, 2007

First Submitted That Met QC Criteria

August 29, 2007

First Posted (Estimate)

August 30, 2007

Study Record Updates

Last Update Posted (Estimate)

February 5, 2016

Last Update Submitted That Met QC Criteria

January 8, 2016

Last Verified

January 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AT9283/0002
  • 2006-0177

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Acute Myeloid Leukemia

Clinical Trials on AT9283

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Philippines

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe