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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Ambit Biosciences Corporation
ClinicalTrials.gov Identifier:
NCT00989261
First received: October 1, 2009
Last updated: November 5, 2013
Last verified: November 2013
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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 Ambit Biosciences Corporation:

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. ] [ Designated as safety issue: No ]
  • Complete remission rate, defined as the confirmed rate of CR. [ Time Frame: Interim analysis following recruitment of 60 patients. Final analysis following study completion. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of remission [ Time Frame: Interim analysis following recruitment of 60 patients. Final analysis following study completion. ] [ Designated as safety issue: No ]
  • Remission rates for all categories of remission [ Time Frame: Interim analysis following recruitment of 60 patients. Final analysis following study completion. ] [ Designated as safety issue: No ]
  • Disease-free survival [ Time Frame: Interim analysis following recruitment of 60 patients. Final analysis following study completion. ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Interim analysis following recruitment of 60 patients. Final analysis following study completion. ] [ Designated as safety issue: No ]
  • Treatment induction and post induction treatment-related mortality [ Time Frame: Interim analysis following recruitment of 60 patients. Final analysis following study completion. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]

Estimated Enrollment: 300
Study Start Date: November 2009
Estimated Study Completion Date: February 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AC220

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.

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

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
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
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: NCT00989261

  Show 85 Study Locations
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

Responsible Party: Ambit Biosciences Corporation
ClinicalTrials.gov Identifier: NCT00989261     History of Changes
Other Study ID Numbers: AC220-002
Study First Received: October 1, 2009
Last Updated: November 5, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Ambit Biosciences Corporation:
AML
AC220
acute
FLT3
inhibitor
kinase
leukemia
leukaemia
myeloid
relapsed
refractory

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

ClinicalTrials.gov processed this record on October 19, 2014