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

Last updated: August 1, 2024
Sponsor: Astex Pharmaceuticals, Inc.
Overall Status: Terminated

Phase

1/2

Condition

White Cell Disorders

Acute Myeloid Leukemia

Lymphoproliferative Disorders

Treatment

AT9283

Clinical Study ID

NCT00522990
AT9283/0002
2006-0177
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

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 unsuitablefor or refuse standard therapy CML in chronic phase, accelerated phase or blast crisis that is resistant orrefractory 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 inadequatelycontrolled 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 ofpost-menopausal status (post-menopausal status is defined as any of the following:natural menopause with menses >1 year ago; radiation induced oophorectomy with lastmenses >1 year ago; chemotherapy induced menopause with 1 year interval since lastmenses

Exclusion

Exclusion Criteria:

  1. Inadequate liver function as demonstrated by serum bilirubin ≥1.5 times the upperlimits of reference range (ULRR) or alanine aminotransferase (ALT) or aspartateaminotransferase (AST) or alkaline phosphatase (ALP) ≥2.5 times the ULRR (or ≥5times 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 byCockcroft-Gault formula. Note there is no requirement to determine a formalcreatinine 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 AT9283being administered (Day 1, dose level 1). Planned use of hydroxyurea other than asis permitted as described in section 11.9.

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

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

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

  7. Active, uncontrolled central nervous system disease

  8. Ischemic heart disease or myocardial infarction or unstable cardiac disease within 3months 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 accessdevices

Study Design

Total Participants: 48
Treatment Group(s): 1
Primary Treatment: AT9283
Phase: 1/2
Study Start date:
September 01, 2006
Estimated Completion Date:
April 30, 2009

Study 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

Connect with a study center

  • University of Alabama at Birmingham

    Birmingham, Alabama 35294
    United States

    Site Not Available

  • The University of Texas, MD Anderson Cancer Center

    Houston, Texas 77030
    United States

    Site Not Available

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