A Phase I Study of AC220 in Patients With Relapsed/Refractory Acute Myeloid Leukemia Regardless of FLT3 Status

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ambit Biosciences Corporation
ClinicalTrials.gov Identifier:
NCT00462761
First received: April 17, 2007
Last updated: January 22, 2013
Last verified: January 2013
  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 1

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

Resource links provided by NLM:


Further study details as provided by Ambit Biosciences Corporation:

Primary Outcome Measures:
  • Safety and tolerability [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    The primary objectives of this study are to:•Determine the safety and tolerability, including dose limiting toxicity (DLT), of oral AC220 when administered daily to patients with relapsed or treatment-refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)


Secondary Outcome Measures:
  • Determine Pharmacokinetic parameters [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Determine the pharmacokinetic (PK) parameters of AC220 under the conditions of this study.The secondary objective of this study is to:•Determine the pharmacodynamic (PD) parameters of orally administered AC220 under the conditions of this study


Enrollment: 76
Study Start Date: January 2007
Study Completion Date: December 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AC220
Determine safety, tolerability and pharmacokinetic (PK) parameters of AC220
Drug: AC220
Powder in bottle formulation supplied as 50mg or 350 mg in glass, crimped serum vials. Requires reconstitution by a pharmacist, and must be stored securely and protected from light.
Other Name: Quizartinib

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
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: NCT00462761

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Georgia
Hematology and Chemotherapy Clinic
T'bilisi, Georgia
Chemotherapy and Immunotherapy Clinic
T'Bilisi, Georgia
Sponsors and Collaborators
Ambit Biosciences Corporation
Investigators
Study Director: Guy Gammon, MB BS, MRCP Interim Chief Medical Officer, Ambit Biosciences Corporation
  More Information

No publications provided by Ambit Biosciences Corporation

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ambit Biosciences Corporation
ClinicalTrials.gov Identifier: NCT00462761     History of Changes
Other Study ID Numbers: CP0001
Study First Received: April 17, 2007
Last Updated: January 22, 2013
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
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
myelomonocytic

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions

ClinicalTrials.gov processed this record on July 26, 2014