An Open-label Study of Quizartinib Monotherapy vs. Salvage Chemotherapy in Acute Myeloid Leukemia (AML) Subjects
Conditions
AML
Conditions: official terms
Leukemia, Myeloid - Leukemia, Myeloid, Acute
Conditions: Keywords
Acute Myeloid Leukemia, AML, FMS-like tyrosine kinase 3, FLT3-ITD, Quizartinib, Leukemia, Tablets
Study Type
Interventional
Study Phase
Phase 3
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Quizartinib Type: Drug
Name: Salvage Chemotherapy Type: Drug
Overall Status
Recruiting
Summary
The primary objective of the study is to determine whether quizartinib monotherapy prolongs overall survival (OS) compared to salvage chemotherapy in subjects with FMS-like tyrosine kinase 3 - Internal Tandem Duplication (FLT3-ITD) positive AML who are refractory to or have relapsed within 6 months, after first-line AML therapy.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

1. Provision of written informed consent approved by the Institutional Review Board (IRB) or Independent Ethics Committee (IEC) with privacy language in accordance with national regulations (e.g., Health Insurance Portability and Accountability Act (HIPAA)) authorization for United States (US) sites prior to any study related procedures, including withdrawal of prohibited medications if applicable.

2. Age ≥18 years at the time of informed consent.

3. Morphologically documented primary Acute Myeloid Leukemia (AML) or AML secondary to Myelodysplastic Syndrome (MDS), as defined by World Health Organization (WHO) criteria, as determined by pathology review at the study site.

4. Refractory, or relapsed within six months AML after first-line therapy, with or without Haematopoietic Stem Cell Transplant (HSCT). First-line therapy can consist of 1 or 2 induction blocks with or without consolidation. Induction therapy must have included at least 1 cycle of an anthracycline/mitoxantrone containing induction block at a standard dose.

5. Presence of the FLT3-ITD activating mutation in bone marrow or peripheral blood (allelic ratio as determined by a central laboratory with a cutoff of >3% FLT3 ITD/total FLT3).

6. Eligibility for pre-selected salvage chemotherapy, according to the Investigator's assessment.

7. Eastern Cooperative Oncology Group (ECOG) performance score 0-2.

8. Discontinuation of prior AML treatment before the start of study treatment (except hydroxyurea, which is permitted for blast control up to the day of starting study treatment) for at least 2 weeks for cytotoxic agents, or for at least 5 half-lives for non cytotoxic agents.

9. Serum creatinine ≤1.5×upper limit of normal (ULN), or glomerular filtration rate >25 mL/min/1.73m2, as calculated with the modified Cockcroft-Gault formula.

10. Serum potassium, magnesium, and calcium (serum calcium corrected for hypoalbuminemia) within institutional normal limits. Subjects with electrolytes outside the normal range will be eligible if these values are corrected upon retesting following any necessary supplementation.

11. Total serum bilirubin ≤1.5×ULN.

12. Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤2.5×ULN.

Exclusion Criteria:

1. Acute Promyelocytic Leukemia (AML subtype M3).

2. AML secondary to prior chemotherapy for other neoplasms, except AML secondary to prior Myelodysplastic Syndrome (MDS).

3. History of another malignancy, unless the candidate has been disease-free for at least 5 years.

4. Persistent, clinically significant > Grade 1 non-hematologic toxicity from prior AML therapy.

5. Clinically significant graft versus host disease (GVHD) or GVHD requiring initiation of treatment or treatment escalation within 21 days, and/or > Grade 1 persistent or clinically significant non hematologic toxicity related to HSCT.

6. History of or current, central nervous system involvement with AML.

7. Clinically significant coagulation abnormality, such as disseminated intravascular coagulation.

8. Prior treatment with quizartinib or participated in a prior quizartinib study.

9. Known presence of a FLT3-D835 mutation at study enrollment. For a candidate who has received prior FLT3-targeted therapy (with the exception of midostaurin), the absence of a baseline FLT3-D835 mutation at study enrollment must be documented.

10. Major surgery within 4 weeks prior to screening.

11. Radiation therapy within 4 weeks prior to screening.

12. Uncontrolled or significant cardiovascular disease

13. Active infection not well controlled by antibacterial or antiviral therapy.

14. Known infection with human immunodeficiency virus, or active hepatitis B or C, or other active clinically relevant liver disease.

15. Unwillingness to receive infusion of blood products according to the protocol.

16. In a man whose sexual partner is a woman of childbearing potential, unwillingness or inability to use an acceptable contraceptive method for the entire study period and for at least 3 months after study completion.

17. In a woman of childbearing potential, unwillingness or inability to use an acceptable contraceptive method for the entire study period and for at least 3 months after study completion.

18. Positive pregnancy test result.

19. Breastfeeding.

20. Medical condition, serious intercurrent illness, or other circumstance that, in the Investigator's judgment, could jeopardize the candidate's safety as a study subject, or that could interfere with study objectives.
Locations
University of Arizona Cancer Center
Tucson, Arizona, United States
Status: Recruiting
City of Hope National Medical Center
Duarte, California, United States
Status: Recruiting
University of California San Diego, Moores Cancer Center
La Jolla, California, United States
Status: Not yet recruiting
UCLA Medical Center
Los Angeles, California, United States
Status: Recruiting
University of Southern California, Norris Comprehensive Cancer Center
Los Angeles, California, United States
Status: Not yet recruiting
UC Davis Cancer Center
Sacramento, California, United States
Status: Recruiting
Stanford University Medical Center Stanford Comprehensive Cancer Center
Stanford, California, United States
Status: Recruiting
Yale University
New Haven, Connecticut, United States
Status: Recruiting
Emory Winship Cancer Institute
Atlanta, Georgia, United States
Status: Recruiting
Northwestern Medical Faculty Foundation
Chicago, Illinois, United States
Status: Recruiting
University of Chicago
Chicago, Illinois, United States
Status: Recruiting
Franciscan Alliance
Indianapolis, Indiana, United States
Status: Recruiting
University of Kansas Medical Center Research Institute Inc
Westwood, Kansas, United States
Status: Recruiting
LSU Health Sciences Center Feist Weiller Cancer Center
Shreveport, Louisiana, United States
Status: Not yet recruiting
University of Maryland
Baltimore, Maryland, United States
Status: Recruiting
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Status: Recruiting
University of Michigan Health System
Ann Arbor, Michigan, United States
Status: Recruiting
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States
Status: Recruiting
Mayo Clinic
Rochester, Minnesota, United States
Status: Recruiting
Washington University School of Medicine
Saint Louis, Missouri, United States
Status: Recruiting
University of Nebraska Medical Center
Omaha, Nebraska, United States
Status: Not yet recruiting
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, United States
Status: Recruiting
Roswell Park Cancer Institute
Buffalo, New York, United States
Status: Recruiting
Columbia University Medical Center
New York, New York, United States
Status: Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Status: Not yet recruiting
University of Rochester
Rochester, New York, United States
Status: Recruiting
NY Medical College
Valhalla, New York, United States
Status: Recruiting
UNC Linebreger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States
Status: Recruiting
Duke Cancer Institute at Duke University Health System
Durham, North Carolina, United States
Status: Not yet recruiting
Wake Forest University Baptist Health
Winston Salem, North Carolina, United States
Status: Recruiting
Oregon Health and Science University Knight Cancer Institute
Portland, Oregon, United States
Status: Recruiting
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, United States
Status: Recruiting
University of Pennsylvania Health System
Philadelphia, Pennsylvania, United States
Status: Recruiting
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States
Status: Not yet recruiting
Avera Cancer Institute
Sioux Falls, South Dakota, United States
Status: Recruiting
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States
Status: Recruiting
UTSW UT Southwestern
Dallas, Texas, United States
Status: Recruiting
MD Anderson Center, The University of Texas
Houston, Texas, United States
Status: Recruiting
Contact: Jorge E Cortes, MD - 713-794-5783
Swedish Cancer Institute
Seattle, Washington, United States
Status: Recruiting
Westmead Hospital
Australia, New South Wales, Australia
Status: Recruiting
Canberra Hospital and Health Services
Woodend, New South Wales, Australia
Status: Recruiting
The Princess Alexandra Hospital
Brisbane, Queensland, Australia
Status: Recruiting
Royal Adelaide Hospital
Adelaide, South Australia, Australia
Status: Recruiting
The Queen Elizabeth Hospital
Woodville, South Australia, Australia
Status: Recruiting
Alfred Hospital
Melbourne, Victoria, Australia
Status: Recruiting
Royal Melbourne Hospital
Parkville, Victoria, Australia
Status: Recruiting
ZNA Stuivenberg
Antwerpen, BE, Belgium
Status: Recruiting
Algemeen Ziekenhuis Sint-Jen
Belgium, BE, Belgium
Status: Recruiting
UCL St Luc
Brussel, BE, Belgium
Status: Recruiting
Leuven UZ Gasthuisberg
Leuven, BE, Belgium
Status: Recruiting
Hopital Erasme
Brussel, Belgium
Status: Not yet recruiting
University of Alberta Hospital
Edmonton, Alberta, Canada
Status: Recruiting
Vancouver General Hospital
Vancouver, British Columbia, Canada
Status: Recruiting
Princess Margaret Cancer Centre Princess Margaret Hospital
Toronto, Ontario, Canada
Status: Recruiting
CHU de Caen
Caen, FR, France
Status: Recruiting
Centre Hospitalier Universitaire Grenoble Hopital Michalon
Grenoble, FR, France
Status: Recruiting
Centre Hospitalier de Versailles
Le Chesnay, FR, France
Status: Recruiting
Hopital de la Conception
Marseille, FR, France
Status: Recruiting
Centre Hospitalier Universitaire Nantes
Nantes, FR, France
Status: Recruiting
Hopital Saint-Antoine
Paris, FR, France
Status: Recruiting
Hôpital Saint Louis
Paris, FR, France
Status: Recruiting
Hopital Haut Leveque Centre Francois Magendie
Pessac, FR, France
Status: Recruiting
Centre Henri-Becquerel
Rouen, FR, France
Status: Recruiting
Centre Hospitalier Universitaire Purpan
Toulouse, FR, France
Status: Recruiting
Charité Campus Virchow Klinikum
Berlin, GM, Germany
Status: Recruiting
Charité Universitätsmedizin Berlin
Berlin, GM, Germany
Status: Recruiting
Klinikum Braunschweig
Braunschweig, GM, Germany
Status: Recruiting
Universitatsklinikum Dresden
Dresden, GM, Germany
Status: Recruiting
Klinikum der Johann Wolfgang-Goethe-Universität
Frankfurt, GM, Germany
Status: Recruiting
Universitätsklinikum Halle
Halle, GM, Germany
Status: Recruiting
Medizinische Hochschule Hannover
Hanover, GM, Germany
Status: Recruiting
Uniklinik Heidelberg Medizinische Klinik und Poliklinik V
Heidelberg, GM, Germany
Status: Recruiting
Universitätsklinikum Jena
Jena, GM, Germany
Status: Recruiting
Universitätsklinikum Leipzig
Leipzig, GM, Germany
Status: Recruiting
University Mainz
Mainz, GM, Germany
Status: Recruiting
Universitätsmedizin Mannheim
Mannheim, GM, Germany
Status: Recruiting
Universitätsklinikum Giessen und Marburg GmbH
Marburg, GM, Germany
Status: Recruiting
LMU München Klinikum Großhadern
Munchen, GM, Germany
Status: Recruiting
Medizinische Klinik A Hämatologie Hämostaseologie Internistische Onkologie und Pneumologie
Münster, GM, Germany
Status: Recruiting
AOU Policlinico Consorziale di Bari
Bari, IT, Italy
Status: Recruiting
Università di Bologna
Bologna, IT, Italy
Status: Recruiting
Arcispedale S Anna
Ferrara, IT, Italy
Status: Recruiting
AOU Careggi
Firenze, IT, Italy
Status: Recruiting
IRCCS Azienda Ospedaliera Universitaria San Martino
Genova, IT, Italy
Status: Recruiting
Opsedale San Martino di Genova
Genova, IT, Italy
Status: Recruiting
Unità Operativa di Ematologia e Unità Operativa CTMO
Italy, IT, Italy
Status: Recruiting
Ospedale San Raffaele
Milan, IT, Italy
Status: Recruiting
Azienda Ospedaliera Universitaria Federico II
Napoli, IT, Italy
Status: Recruiting
Azienda Ospedaliero Universitaria San Luigi Gonzaga
Orbassano, IT, Italy
Status: Recruiting
L'UOC di Ematologia del Policlinico Tor Vergata
Rome, IT, Italy
Status: Recruiting
Policlinico Universitario Agostino Gemelli
Rome, IT, Italy
Status: Recruiting
Ospedale di Circolo-a Fondazione Macchi
Varese, IT, Italy
Status: Recruiting
Azienda Ospedaliero Universitaria Senese, Policlinico S. Maria alle Scotte
Siena, Italy
Status: Recruiting
VU Medisch Centrum
Amsterdam, NE, Netherlands
Status: Recruiting
Universitair Medisch Centrum Groningen
Groningen, NE, Netherlands
Status: Recruiting
Radboud University Medical Center
Nijmegen, NE, Netherlands
Status: Recruiting
Erasmus Medical Center
Rotterdam, NE, Netherlands
Status: Recruiting
Hospital Clinic I Provincial de Barcelona
Barcelona, SP, Spain
Status: Recruiting
Hospital Universitari Germans Trias i Pujol
Barcelona, SP, Spain
Status: Recruiting
Hospital General Universitario Gregorio Marañon
Madrid, SP, Spain
Status: Recruiting
Hospital Universitario La Paz
Madrid, SP, Spain
Status: Recruiting
Hospital Son Espases
Mallorca, SP, Spain
Status: Recruiting
Complejo Hospitalario de Navarra
Pamplona, SP, Spain
Status: Recruiting
Hospital Clínico Universitario de Salamanca
Salamanca, SP, Spain
Status: Recruiting
Hospital Universitario Virgen del Rocio
Sevilla, SP, Spain
Status: Recruiting
Hospital La Fe
Valencia, SP, Spain
Status: Recruiting
Bristol Haematology and Oncology Centre
Bristol, England, United Kingdom
Status: Recruiting
Saint James University Hospital
Leeds, England, United Kingdom
Status: Recruiting
Imperial College Healthcare NHS Trust, Hammersmith Hospital
London, England, United Kingdom
Status: Recruiting
King's College Hospital
London, England, United Kingdom
Status: Recruiting
Nottingham City Hospital NHS Trust
Nottingham, England, United Kingdom
Status: Recruiting
Royal Marsden Hospital Sutton
Sutton, England, United Kingdom
Status: Recruiting
Aberdeen Royal Infirmary
Aberdeen, Scotland, United Kingdom
Status: Recruiting
University Hospital of Wales
Cardiff, South Glamorgan, United Kingdom
Status: Recruiting
Queens University
UK, United Kingdom
Status: Recruiting
Start Date
April 2014
Completion Date
February 2016
Sponsors
Ambit Biosciences Corporation
Source
Ambit Biosciences Corporation
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page