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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00462761
Recruitment Status : Completed
First Posted : April 19, 2007
Last Update Posted : November 2, 2015
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Brief Summary:
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 or disease Intervention/treatment Phase
Acute Myeloid Leukemia Leukemia Myelodysplastic Syndrome AML MDS Drug: AC220 Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 76 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : January 2007
Actual Primary Completion Date : March 2009
Actual Study Completion Date : December 2009

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Safety and tolerability [ Time Frame: 6 months ]
    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 :
  1. Determine Pharmacokinetic parameters [ Time Frame: 6 months ]
    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

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00462761

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
Chemotherapy and Immunotherapy Clinic
T'Bilisi, Georgia
Hematology and Chemotherapy Clinic
T'bilisi, Georgia
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Study Director: Guy Gammon, MB BS, MRCP Interim Chief Medical Officer, Ambit Biosciences Corporation

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Daiichi Sankyo, Inc. Identifier: NCT00462761     History of Changes
Other Study ID Numbers: CP0001
First Posted: April 19, 2007    Key Record Dates
Last Update Posted: November 2, 2015
Last Verified: October 2015

Keywords provided by Daiichi Sankyo, Inc.:
class III

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