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

  Hide Study Locations
Locations
United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21231
University of Maryland
Baltimore, Maryland, United States, 21201
United States, Michigan
University of Michigan Medical Center
Ann Arbor, Michigan, United States, 48109
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Columbia University
New York, New York, United States, 10032
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Abramson Cancer Center
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
The Vanderbuilt Clinic
Nashville, Tennessee, United States, 37232
Clinical Trials Center
Nashville, Tennessee, United States, 37212
United States, Texas
M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
France
Institut Paoli Calmettes Centre Regional de Lutte Contre le Cancer
Marseille, Cedex 9, France
Hematologie - CHU Purpan
Toulouse, Cedex, France
Centre Hospitalier Regional Universitaire, Hopital de Hautepierre
Alsace, France
Hopital Avicenne
Bobigny, France
Centre Hospitalier Universitaire d'Angers
d'Angers, France
Centre Hospitalier Universitaire Grenoble
Grenoble, France
Centre Hospitalier de Versailles
Le Chesnay, France
Hopital Claude Huriez
Lille, France
Centre Hospitalier Universitaire Limoges
Limoges, France
Hopital Edouard Herriot
Lyon, France
Hopital Saint-Louis
Paris, France
Hopital Saint-Antoine
Paris, France
Hopital Haut-Leveque
Pessac, France
Centre Henry Becquerel, Service d'Hematologie
Rouen, France
Centre Hospitalier Universitaire Brabois
Vandoeuvre les Nancy, France
Germany
Charite, Campus Benjamin Franklin
Berlin, Germany
Charite Campus Virchow Klinikum
Berlin, Germany
Universitatsklinikum Bonn
Bonn, Germany, 5311
Unikliniksklinikum Carl Gustav Carus
Dresden, Germany
Uniklinik Essen, Westdeutsches Tumorzentrum
Essen, Germany
Klinikum der Johann Wolfgang Goethe Universitat
Frankfurt am Main, Germany
Asklepios Klinik St Georg
Hamburg, Germany
Medizinische Hochschule Hannover
Hannover, Germany
Universitatsklinikum Heidelberg
Heidelberg, Germany
Universitatsklinikum Jena
Jena, Germany
Universitatsklinikum Leipzig Selbstandige Abteilung fur Hamatologie
Leipzig, Germany
Universitatsklinikum Magdeburg
Magdeburg, Germany
Universitatsklinikum Mannheim
Mannheim, Germany
Philipps-Universitat Marburg
Marburg, Germany
Klinikum rechts der Isar, Technische Universitat Munchen
Munchen, Germany
Universitatsklinikum Munster
Munster, Germany
Universitatsklinikum Regensburg Abteilung fur Hamatologie
Regensburg, Germany
Robert-Bosch-Krankenhaus GmbH
Stuttgart, Germany
Universitatsklinikum Tubingen
Tubingen, Germany
Universitatsklinikum Ulm
Ulm, Germany
Universitatsklinikum Wurzburg
Wurzburg, Germany
Italy
Instituto Di Ematologia "L.Ea. Seragnoli"
Bologna, Italy
Unita Trapianti di Midollo Osseo per Adulti
Brescia, Italy
Presidio Ospedaliero "A. Businco" - Centro di Riferimento Oncologico Regionale
Cagliari, Italy
Azienda Ospedaliera-Universitaria Vittorio Emanuele-Ferrarotto
Catania, Italy
Azienda Ospedaliera Universitaria San Martino
Genova, Italy
Farmacia Ospidaliera
Orbassano, Italy
Ospedale Civile S. Maria delle Croci
Ravenna, Italy, 48100
Universita Degli Studi di Roma Tor Vergata
Roma, Italy
Ospedale Sant Eugenio
Roma, Italy, 00144
Azienda Ospedaliero Universitaria Senese
Siena, Italy
Azienda Ospedaliero Universitaria S. Maria della Misericordia di Udine, Clinica Ematologica
Udine, Italy
Netherlands
Utrecht University Medical Centre, Dept. of Hematology
CX Utrecht, Netherlands
University Medical Center Groningen
Groningen, Netherlands
Poland
Dolnoslaskie Centrum Transplantacji Komorkowych z
Wroclaw, Poland
Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain
Hospital Clinic i Provincial de Barcelona
Barcelona, Spain
Institut Catala d'Oncologia del Hospital Universitari Germans
Barcelona, Spain
Instituto Catalan de Oncologia-Hospital Universitari de Girona
Girona, Spain
Hospital General Universitario Gregorio Maranon
Madrid, Spain
Hospital de la Princesa, Servicio de Hematologia
Madrid, Spain
Clinica Universidad de Navarra
Navarra, Spain
Hospital Universitario de Salamanca, Hospital Clinico, Servicio de Hematologia
Salamanca, Spain
Hospital La Fe, Servicio de Hematologia
Valencia, Spain
United Kingdom
Addenbrook's Hospital
Cambridge, United Kingdom
Castle Hill Hospital
Cottingham, United Kingdom, HU 16 5JQ
Saint James University Hospital, Institute of Oncology
Leeds, United Kingdom, LS9 7TF
Hanmmersmith Hospital, Dept. of Hematology
London, United Kingdom
Nottingham University Hospitals NHS Trust
Nottigham, United Kingdom, NG5 1PB
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
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on August 21, 2014