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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier:
NCT00989261
First received: October 1, 2009
Last updated: August 23, 2017
Last verified: August 2017
October 1, 2009
August 23, 2017
November 2009
September 2012   (Final data collection date for primary outcome measure)
  • 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. ]
Overall complete remission rate and complete remission rate [ Time Frame: Interim analysis following recruitment of 60 patients. Final analysis following study completion. ]
Complete list of historical versions of study NCT00989261 on ClinicalTrials.gov Archive Site
  • 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. ]
  • 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 phosph-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. ]
Not Provided
Not Provided
 
Efficacy Study for AC220 to Treat Acute Myeloid Leukemia (AML)
Phase 2 Open-Label, AC220 Monotherapy Efficacy (ACE) Study in Patients With Acute Myeloid Leukemia (AML) With and Without FLT3-ITD Activating Mutations
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).
Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Acute Myeloid Leukemia
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 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.

    Intervention: Drug: Compound AC220
  • 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.
    Intervention: Drug: Compound AC220
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
333
September 2012
September 2012   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 85 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Canada,   France,   Germany,   Italy,   Netherlands,   Poland,   Spain,   United Kingdom,   United States
 
 
NCT00989261
AC220-002
Yes
Not Provided
Not Provided
Daiichi Sankyo, Inc.
Daiichi Sankyo, Inc.
Not Provided
Study Director: Interim Chief Medical Officer Ambit Biosciences Corporation
Daiichi Sankyo, Inc.
August 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP