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

This study has been terminated.
(Recommended Phase II dose determined)
Sponsor:
Information provided by (Responsible Party):
Astex Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00522990
First received: August 29, 2007
Last updated: February 6, 2013
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Chronic Myeloid Leukemia
Myelodysplastic Syndromes
Myelofibrosis
Drug: AT9283
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Astex Pharmaceuticals:

Primary Outcome Measures:
  • Safety and tolerability [ Time Frame: Up to 30 days after completing therapy with AT9283 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 48
Study Start Date: September 2006
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Refractory Hematological Malignancies
Drug: AT9283
Three weekly intravenous administration of AT9283

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00522990

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Texas
The University of Texas, MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Astex Pharmaceuticals
Investigators
Principal Investigator: Hagop Kantarjian, MD The University of Texas M. D. Anderson Cancer Center (MDACC)
  More Information

No publications provided

Responsible Party: Astex Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00522990     History of Changes
Other Study ID Numbers: AT9283/0002, 2006-0177
Study First Received: August 29, 2007
Last Updated: February 6, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Primary Myelofibrosis
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Precancerous Conditions

ClinicalTrials.gov processed this record on August 28, 2014