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A Phase I Study of AC220 in Patients With Relapsed/Refractory Acute Myeloid Leukemia Regardless of FLT3 Status
This study is currently recruiting participants.
Verified by Ambit Biosciences Corporation, September 2007
Sponsored by: Ambit Biosciences Corporation
Information provided by: Ambit Biosciences Corporation
ClinicalTrials.gov Identifier: NCT00462761
  Purpose

Patients will receive oral AC220 daily for 14 days to study the side effects, tolerability and best dose for treating relapsed or refractory acute myeloid leukemia, regardless of FLT3 status.


Condition Intervention Phase
Acute Myeloid Leukemia
Leukemia
Myelodysplastic Syndrome
AML
MDS
Drug: AC220
Phase I

MedlinePlus related topics: Leukemia, Adult Acute Leukemia, Adult Chronic
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Dose Comparison, Single Group Assignment, Safety/Efficacy Study
Official Title: Phase I Open-Label, Sequential Dose Escalation Study Investigating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AC220 When Administered Daily to Patients With Relapsed or Refractory Acute Myeloid Leukemia

Further study details as provided by Ambit Biosciences Corporation:

Primary Outcome Measures:
  • Safety, tolerability, DLT and PK parameters

Secondary Outcome Measures:
  • PD parameters

Estimated Enrollment: 20
Study Start Date: January 2007
Estimated Study Completion Date: December 2007
Detailed Description:

This is a multi-center clinical study conducted in the USA and possibly two international sites. It is open-label, dose escalation study designed to characterize the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of orally administered AC220 as a single agent given daily for 14 days. Cohorts of 3 patients receive AC220 until dose limiting toxicity is noted (DLT). At that point cohorts will expand to 6 patients until MTD is determined. Patients not experiencing DLT or significant disease progression at Day 15 may continue receiving AC220 at the discretion of the Investigator and Sponsor. FLT3 positive and negative patients are allowed to participate.

  Eligibility

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

Inclusion Criteria:

  1. Males and females age ≥ 18 years;
  2. Histopathologically documented primary or secondary AML, as defined by WHO criteria (Jaffe et al, 2001), confirmed by pathology review at treating institution, meeting at least one of the following:

    1. Refractory to at least 1 cycle of induction chemotherapy, or
    2. Relapsed after at least 1 cycle of induction chemotherapy, or
    3. Patient is not, according to the clinical judgment of the Principal Investigator, a candidate for induction chemotherapy due to age, comorbidity, or other factors;
  3. Patients for whom no standard therapies are anticipated to result in a durable remission, or who have failed potentially curative therapy, or who refuse standard therapy or patients for whom there is no known therapy of documented treatment benefit;
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-3;
  5. In the absence of rapidly progressing disease, the interval from prior treatment to time of AC220 administration should be at least 2 weeks for cytotoxic agents (other than hydroxyurea, per Section 8.8), or at least 5 half-lives for noncytotoxic agents;
  6. Persistent chronic clinically significant toxicities from prior chemotherapy or surgery must be less than Grade 2;
  7. Serum creatinine ≤ 2.0 mg/dL;
  8. Total serum bilirubin ≤ 1.5 × ULN unless considered due to Gilbert's syndrome or leukemic organ involvement;
  9. Serum AST or ALT ≤ 3.0 × ULN unless considered due to leukemic organ involvement;
  10. Females of childbearing potential must have a negative pregnancy test (urine β-hCG);
  11. Females of childbearing potential and sexually mature males must agree to use a medically accepted method of contraception throughout the study;
  12. Written informed consent must be provided.

Exclusion Criteria:

  1. Histologic diagnosis of acute promyelocytic leukemia;
  2. Clinically active central nervous system leukemia;
  3. Persistent clinically significant toxicity from prior chemotherapy that is Grade 2 or higher by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v3);
  4. Bone marrow transplant within 2 months prior to study;
  5. Active, uncontrolled infection;
  6. Major surgery within 4 weeks prior to study;
  7. Radiation therapy within 4 weeks prior to, or concurrent with, study;
  8. Human immunodeficiency virus positivity;
  9. Active hepatitis B or C or other active liver disease;
  10. Women who are pregnant, lactating, or unwilling to use contraception if of childbearing potential;
  11. Medical condition, serious intercurrent illness, or other extenuating circumstance that, in the judgment of the Principal Investigator, could jeopardize patient safety or interfere with the objectives of the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00462761

Contacts
Contact: Ambit Clinical Research & Development 858-334-2173 cp0001@ambitbio.com
Contact: Secondary Ambit Contact 858-334-2100

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Principal Investigator: James M Foran, MD FRCP(C)            
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
Principal Investigator: Marcel P Devetten, MD            
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Jorge Cortes, MD            
Georgia
Hematology and Chemotherapy Clinic Recruiting
T'bilisi, Georgia
Principal Investigator: Mamia Zodelava, MD PhD            
Chemotherapy and Immunotherapy Clinic Recruiting
T'Bilisi, Georgia
Principal Investigator: Darejan Ghirdaladze, MD PhD            
Sponsors and Collaborators
Ambit Biosciences Corporation
  More Information

No publications provided

Study ID Numbers: CP0001
Study First Received: April 17, 2007
Last Updated: September 24, 2007
ClinicalTrials.gov Identifier: NCT00462761  
Health Authority: United States: Food and Drug Administration

Keywords provided by Ambit Biosciences Corporation:
RTK
kinase
inhibitor
tyrosine
acute
FLT3
AC220
pharmacokinetic
pharmacokinetics
PK
pharmacodynamic
pharmacodynamics
mutations
PD
mutations
receptor
class III
relapsed
refractory
t(8;21)
q22;q22
AML1/ETO
t(16;16
p13;q22
CBFbeta/MYH11
inv(16)
p13q22
11q23
dysplasia
myeloid

Study placed in the following topic categories:
Myelodysplastic syndromes
Myelofibrosis
Precancerous Conditions
Hematologic Diseases
Myelodysplastic Syndromes
Leukemia, Myeloid
Di Guglielmo's syndrome
Leukemia, Myeloid, Acute
Myeloid Metaplasia
Leukemia
Preleukemia
Leukemia, Erythroblastic, Acute
Acute erythroblastic leukemia
Bone Marrow Diseases
Acute myelocytic leukemia

Additional relevant MeSH terms:
Neoplasms
Pathologic Processes
Disease
Neoplasms by Histologic Type
Syndrome

ClinicalTrials.gov processed this record on February 12, 2009