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Efficacy Study for AC220 to Treat Acute Myeloid Leukemia (AML) (ACE)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00989261
First Posted: October 5, 2009
Last Update Posted: August 25, 2017
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.
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.
  Purpose
AC220 will be administered as a once daily oral solution given continuously as 28-day treatment cycles, without any rest periods, until disease progression, relapse, intolerance to the drug, or elective allogeneic hematopoietic stem cell transplantation (HSCT).

Condition Intervention Phase
Acute Myeloid Leukemia Drug: Compound AC220 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2 Open-Label, AC220 Monotherapy Efficacy (ACE) Study in Patients With Acute Myeloid Leukemia (AML) With and Without FLT3-ITD Activating Mutations

Resource links provided by NLM:


Further study details as provided by Daiichi Sankyo, Inc.:

Primary Outcome Measures:
  • Composite complete remission rate (CRc), defined as the confirmed rate of complete remission (CR) plus complete remission with incomplete platelet (CRp) or incomplete hematological recovery (CRi). [ Time Frame: Interim analysis following recruitment of 60 patients. Final analysis following study completion. ]
  • Complete remission rate, defined as the confirmed rate of CR. [ Time Frame: Interim analysis following recruitment of 60 patients. Final analysis following study completion. ]

Secondary Outcome Measures:
  • Duration of remission [ Time Frame: Interim analysis following recruitment of 60 patients. Final analysis following study completion. ]
  • Remission rates for all categories of remission [ Time Frame: Interim analysis following recruitment of 60 patients. Final analysis following study completion. ]
  • Disease-free survival [ Time Frame: Interim analysis following recruitment of 60 patients. Final analysis following study completion. ]
  • Overall survival [ Time Frame: Interim analysis following recruitment of 60 patients. Final analysis following study completion. ]
  • Treatment induction and post induction treatment-related mortality [ Time Frame: Interim analysis following recruitment of 60 patients. Final analysis following study completion. ]
  • Safety and tolerability of AC220 as determined by adverse event reporting, clinical laboratory results, vital signs, physical exams, and electrocardiograms (ECG). [ Time Frame: Interim analysis following recruitment of 60 patients. Final analysis following study completion. ]
  • Pharmacokinetic analysis of AC220. Analysis of phospho-FLT3 and other pharmacodynamic markers. [ Time Frame: Interim analysis following recruitment of 60 patients. Final analysis following study completion. ]
  • Impact of AC220 on hematological improvement, bridge to transplant, duration of leukemia control, blood and platelet transfusions, infections, days of hospitalization, performance status [ Time Frame: Interim analysis following recruitment of 60 patients. Final analysis following study completion. ]
  • Pharmacogenetic analyses, correlation of remission with FLT3-ITD allelic ratio and other parameters using other assays. [ Time Frame: Interim analysis following recruitment of 60 patients. Final analysis following study completion. ]

Enrollment: 333
Study Start Date: November 2009
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AC220 cohort1

FLT3-ITD positive and negative populations will be divided into 2 cohorts as follows:

Cohort 1: Patients who are ≥60 years of age who are relapsed after 1 first-line chemotherapy regimen (with or without consolidation) and after CR1 <12 months or are primary refractory to first-line chemotherapy.

Drug: Compound AC220
Precomplexed powder in bottle formulation supplied as 200 mg in a 60 cc polyethylene terephthalate (PET) plastic bottle. Requires reconstitution by a pharmacist, must be stored securely, and protected from light.
Other Name: AC010220 × 2HCl, oral powder for reconstitution
Experimental: AC220 cohort2
Cohort 2: Patients who are ≥18 years of age (note this includes patients ≥60 years of age) who are relapsed or refractory after 1 second-line (salvage) regimen or are relapsed or refractory after HSCT.
Drug: Compound AC220
Precomplexed powder in bottle formulation supplied as 200 mg in a 60 cc polyethylene terephthalate (PET) plastic bottle. Requires reconstitution by a pharmacist, must be stored securely, and protected from light.
Other Name: AC010220 × 2HCl, oral powder for reconstitution

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Current enrollment is open only to FLT3-ITD positive, Cohort 1.

Inclusion Criteria:

  1. Males and females age ≥18 years in second relapse or refractory.
  2. Males and females age ≥60 years in first relapse or refractory.
  3. Must have baseline bone marrow sample taken.
  4. Morphologically documented primary AML or AML secondary to myelodysplastic syndrome (MDS with ≥20% bone marrow or peripheral blasts), as defined by the World Health Organization (WHO) criteria, confirmed by pathology review at treating institution.
  5. Able to swallow the liquid study drug.
  6. ECOG performance status of 0 to 2
  7. In the absence of rapidly progressing disease, the interval from prior treatment to time of AC220 administration will be at least 2 weeks for cytotoxic agents or at least 5 half-lives for noncytotoxic agents. The use of chemotherapeutic or antileukemic agents other than hydroxyurea is not permitted during the study with the possible exception of intrathecal (IT) therapy at the discretion of the Investigator and with the agreement of the Sponsor.
  8. Persistent chronic clinically significant non-hematological toxicities from prior treatment must be ≤Grade 1.
  9. Prior therapy with FLT3 inhibitors is permitted, except previous treatment with AC220.
  10. Serum creatinine ≤1.5 × ULN and glomerular filtration rate (GFR) > 30 mL/min
  11. Serum potassium, magnesium, and calcium levels should be at least within institutional normal limits.
  12. Total serum bilirubin ≤1.5 × ULN
  13. Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤2.5 × ULN
  14. Females of childbearing potential must have a negative pregnancy test (urine β-hCG).
  15. Females of childbearing potential and sexually mature males must agree to use a medically accepted method of contraception throughout the study.
  16. Written informed consent must be provided.

Exclusion Criteria:

  1. Patients over the age of 85 years except at the discretion of the Investigator and with agreement of the Sponsor.
  2. Diagnosis of acute promyelocytic leukemia
  3. Diagnosis of chronic myelogenous leukemia (CML) in blast crisis
  4. AML in relapse or refractory after 3 or more previous lines of chemotherapy (and/or HSCT) treatment
  5. AML or antecedent MDS secondary to prior chemotherapy
  6. Persistent clinically significant non-hematological toxicity that is Grade >1 by NCI CTCAE v4 from prior chemotherapy
  7. Patients who have had HSCT and are within 100 days of transplant and/or are still taking immunosuppressive drugs and/or have clinically significant graft-versus-host disease requiring treatment and/or have >Grade 1 persistent non hematological toxicity related to the transplant
  8. Clinically active central nervous system (CNS) leukemia. Patients with CNS leukemia, which is controlled, but who are still receiving IT therapy at study entry may be considered eligible and continue receive IT therapy at the discretion of the Investigator and with agreement of the Sponsor.
  9. Patients who have previously received AC220
  10. Disseminated intravascular coagulation (DIC) (diagnosis by laboratory or clinical assessment)
  11. Major surgery within 4 weeks prior to enrollment in the study
  12. Radiation therapy within 4 weeks prior to, or concurrent with study
  13. Use of concomitant drugs that prolong QT/QTc interval and/or are CYP3A4 inhibitors are prohibited with the exception of antibiotics, antifungals, and other antimicrobials that are used as standard of care to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the patient.
  14. Uncontrolled or significant cardiovascular disease
  15. Women who are pregnant, lactating, or unwilling to use contraception if of childbearing potential
  16. Men who are unwilling to use contraception if their partners are of childbearing potential
  17. Active, uncontrolled infection
  18. Human immunodeficiency virus positivity
  19. Active hepatitis B or C or other active liver disease
  20. History of cancer, except Stage 1 cervix or nonmelanotic skin cancer, with the possible exception of patients in complete remission
  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT00989261


  Show 85 Study Locations
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Investigators
Study Director: Interim Chief Medical Officer Ambit Biosciences Corporation
  More Information

Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT00989261     History of Changes
Other Study ID Numbers: AC220-002
First Submitted: October 1, 2009
First Posted: October 5, 2009
Last Update Posted: August 25, 2017
Last Verified: August 2017

Keywords provided by Daiichi Sankyo, Inc.:
AML
AC220
acute
FLT3
inhibitor
kinase
leukemia
leukaemia
myeloid
relapsed
refractory

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms