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A Phase 1 Study of AC220 (ASP2689) as Maintenance Therapy in Subjects With Acute Myeloid Leukemia Who Have Been Treated With an Allogeneic Hematopoietic Stem Cell Transplant

Phase 1
18 Years
Open (Enrolling)
Leukemia, Myeloid, Acute,

Thank you

Trial Information

A Phase 1 Study of AC220 (ASP2689) as Maintenance Therapy in Subjects With Acute Myeloid Leukemia Who Have Been Treated With an Allogeneic Hematopoietic Stem Cell Transplant

This is a two-part, sequential group dose escalation study.

In Part 1, subjects will be enrolled into successive cohorts to determine the maximum
tolerated dose (MTD). Dose escalation decision will be made based on dose limiting
toxicities (DLTs) that occur in subjects treated to date at a given dose level. In Part 2, a
confirmation cohort will be opened to confirm the safety at the MTD.

Subjects who have had an allogeneic Hematopoietic Stem Cell Transplant (HSCT) will enter
treatment with AC220 between 30 to 60 days after receiving allogeneic HSCT. AC220 will be
administered every day, with 28 consecutive days defined as a treatment cycle. Subjects may
receive up to 24 continuous treatment cycles. Subjects will have study visits each week for
the first 2 cycles, and then on Day 1 of each cycle after that.

Inclusion Criteria:

- Subject has a diagnosis of acute myeloid leukemia (AML) according to WHO
classification (2008) and has received a high dose or a reduced intensity
conditioning allogeneic Hematopoietic Stem Cell Transplant (HSCT) during first or
second remission and within 30 to 60 days prior to first dose of AC220. Donors may be
human leukocyte antigen (HLA)-matched for HLA-A, B, C, DRB1, and DQB1 by high
resolution typing, related or unrelated (only a single allele disparity will be
allowed for HLA-A, B, or C as defined by high resolution typing) Note: more than one
HSCT is allowed

- Subject must be in morphologic remission (< 5% marrow blasts) and without active
central nervous system (CNS) AML within 14 days prior to first dose of AC220

- Subject must have CD3 donor chimerism > 50 % at Screening

- Subject has a Karnofsky Performance Status (KPS) of ≥ 60

- Subject must have absolute neutrophil count (ANC) > 1000/mm3 and platelet count >
50,000/mm3 without platelet transfusion support within 2 weeks prior to first dose

- Subject must have adequate renal, hepatic, and coagulation parameters as indicated by
the following laboratory values:

- Alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase
(ALT) ≤ 2.5 x institutional upper limit of normal (ULN)

- Total bilirubin ≤ 1.5 x institutional ULN

- Serum creatinine ≤ 1.5 x institutional ULN or an estimated glomerular filtration
rate (eGFR) of > 50 ml/min as calculated by the Modification of Diet in Renal
Disease (MDRD) equation

- Female subjects must be either:

- Post-menopausal (defined as at least 1 year without any menses) prior to
Screening or

- Premenarchal prior to Screening or

- Documented surgically sterile or status post hysterectomy (at least 1 month
prior to screening) or

- If of childbearing potential, must have a negative urine pregnancy test at
Screening and must be using highly effective contraception. All females of
childbearing potential will be required to use highly effective contraception
consisting of two forms of birth control (one of which must be a barrier
method) starting at Screening and throughout the study period and for 28 days
[or five half lives of the study drug whichever is longer] after the final study
drug administrations

- Female subjects must not be lactating and must not be breastfeeding at Screening or
during the study period and for 28 days [or five half lives of the study drug
whichever is longer] after final study drug administration.

- Subject is able to comply with study procedures and follow-up examinations

Exclusion Criteria:

- Subject received AC220 and relapsed during treatment with AC220

- Subject has active ≥ Grade 2 graft versus host disease (GVHD)

- Subject has received concurrent chemotherapy, immunotherapy, or radio-therapy within
21 days prior to the first dose of AC220, or any antineoplastic therapy that is
considered to be investigational (i.e., used for non-approved indications(s) and in
the context of a research investigation) within 30 days or 5 half-lives (whichever is
longer) prior to the first dose of study drug

- Subject requires treatment with concomitant drugs that prolong QT/QTc interval or
strong cytochrome P-3A4 (CYP3A4) inhibitors or inducers with the exception of
immunosuppressants, antibiotics, antifungals, and antivirals that are used as
standard of care post-transplant or to prevent or treat infections and other such
drugs that are considered absolutely essential for the care of the subject

- Subject requires treatment with anticoagulant therapy

- Subject has a known positive test for human immunodeficiency virus, hepatitis C, or
hepatitis B surface antigen

- Subject had major surgery within 4 weeks prior to first dose of AC220

- Subject has uncontrolled or significant cardiovascular disease

- Subject has an active acute fungal, bacterial, or other infection that is
unresponsive to therapy

- Subject has participated in any interventional clinical study or has been treated
with any investigational drugs within 30 days or 5 half lives whichever is longer,
prior to the initiation of Screening.

- Subject has any medical, psychiatric, addictive or other kind of disorder which
compromises the ability of the subject to give written informed consent and/or to
comply with procedures

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Incidence of dose limiting toxicity (DLT)

Outcome Description:

From first dose through last dose of Cycle 2

Outcome Time Frame:

up to Day 56

Safety Issue:


Principal Investigator

Senior Medical Director

Investigator Role:

Study Director

Investigator Affiliation:

Astellas Pharma Global Development


United States: Food and Drug Administration

Study ID:




Start Date:

April 2012

Completion Date:

March 2015

Related Keywords:

  • Leukemia, Myeloid, Acute,
  • AC220
  • Acute Myeloid Leukemia (AML)
  • Transplantation
  • Stem Cell Transplantation
  • Allogeneic Transplantation
  • FMS-like tyrosine kinase (FLT3)
  • FMS-like tyrosine kinase (FLT3) Inhibitor
  • Kinase
  • Kinase Inhibitor
  • Pharmacokinetics
  • ASP2689
  • quizartinib
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid



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