Efficacy Study for AC220 to Treat Acute Myeloid Leukemia (AML) (ACE)
Acute Myeloid Leukemia
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring AML, AC220, acute, FLT3, inhibitor, kinase, leukemia, leukaemia, myeloid, relapsed, refractory
Eligibility Criteria
Current enrollment is open only to FLT3-ITD positive, Cohort 1.
Inclusion Criteria:
- Males and females age ≥18 years in second relapse or refractory.
- Males and females age ≥60 years in first relapse or refractory.
- Must have baseline bone marrow sample taken.
- 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.
- Able to swallow the liquid study drug.
- Eastern Cooperative Oncology Group performance status of 0 to 2
- 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.
- Persistent chronic clinically significant non-hematological toxicities from prior treatment must be ≤Grade 1.
- Prior therapy with FLT3 inhibitors is permitted, except previous treatment with AC220.
- Serum creatinine ≤1.5 × upper limit of normal (ULN) and glomerular filtration rate (GFR) > 30 mL/min
- Serum potassium, magnesium, and calcium levels should be at least within institutional normal limits.
- Total serum bilirubin ≤1.5 × ULN
- Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤2.5 × ULN
- Females of childbearing potential must have a negative pregnancy test (urine β-hCG).
- Females of childbearing potential and sexually mature males must agree to use a medically accepted method of contraception throughout the study.
- Written informed consent must be provided.
Exclusion Criteria:
- Patients over the age of 85 years except at the discretion of the Investigator and with agreement of the Sponsor.
- Diagnosis of acute promyelocytic leukemia
- Diagnosis of chronic myelogenous leukemia (CML) in blast crisis
- AML in relapse or refractory after 3 or more previous lines of chemotherapy (and/or HSCT) treatment
- AML or antecedent MDS secondary to prior chemotherapy
- Persistent clinically significant non-hematological toxicity that is Grade >1 by NCI CTCAE v4 from prior chemotherapy
- 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
- 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.
- Patients who have previously received AC220
- Disseminated intravascular coagulation (DIC) (diagnosis by laboratory or clinical assessment)
- Major surgery within 4 weeks prior to enrollment in the study
- Radiation therapy within 4 weeks prior to, or concurrent with study
- Use of concomitant drugs that prolong the time between the start of the Q wave and the end of the T wave (QT)/corrected interval between the Q wave and T wave (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.
- Uncontrolled or significant cardiovascular disease
- Women who are pregnant, lactating, or unwilling to use contraception if of childbearing potential
- Men who are unwilling to use contraception if their partners are of childbearing potential
- Active, uncontrolled infection
- Human immunodeficiency virus positivity
- Active hepatitis B or C or other active liver disease
- History of cancer, except Stage 1 cervix or nonmelanotic skin cancer, with the possible exception of patients in complete remission
Sites / Locations
- University of California, San Francisco
- Northwestern Memorial Hospital
- Rush University Medical Center
- Indiana University
- University of Iowa Hospitals and Clinics
- University of Maryland
- Johns Hopkins Hospital
- University of Michigan Medical Center
- Karmanos Cancer Institute
- Mayo Clinic
- Roswell Park Cancer Institute
- Columbia University
- Oregon Health and Science University
- Milton S. Hershey Medical Center
- Abramson Cancer Center
- Clinical Trials Center
- The Vanderbuilt Clinic
- M.D. Anderson Cancer Center
- Seattle Cancer Care Alliance
- University of Wisconsin Hospital and Clinics
- Princess Margaret Hospital
- Institut Paoli Calmettes Centre Regional de Lutte Contre le Cancer
- Hematologie - CHU Purpan
- Hopital Avicenne
- Centre Hospitalier Universitaire d'Angers
- Centre Hospitalier Universitaire Grenoble
- Centre Hospitalier de Versailles
- Hopital Claude Huriez
- Centre Hospitalier Universitaire Limoges
- Hopital Edouard Herriot
- Hopital Saint-Antoine
- Hopital Saint-Louis
- Hopital Haut-Leveque
- Centre Henry Becquerel, Service d'Hematologie
- Centre Hospitalier Regional Universitaire, Hopital de Hautepierre
- Centre Hospitalier Universitaire Brabois
- Charite Campus Virchow Klinikum
- Charite, Campus Benjamin Franklin
- Universitatsklinikum Bonn
- Unikliniksklinikum Carl Gustav Carus
- Uniklinik Essen, Westdeutsches Tumorzentrum
- Klinikum der Johann Wolfgang Goethe Universitat
- Asklepios Klinik St Georg
- Medizinische Hochschule Hannover
- Universitatsklinikum Heidelberg
- Universitatsklinikum Jena
- Universitatsklinikum Leipzig Selbstandige Abteilung fur Hamatologie
- Universitatsklinikum Magdeburg
- Universitatsklinikum Mannheim
- Philipps-Universitat Marburg
- Klinikum rechts der Isar, Technische Universitat Munchen
- Universitatsklinikum Munster
- Universitatsklinikum Regensburg Abteilung fur Hamatologie
- Robert-Bosch-Krankenhaus GmbH
- Universitatsklinikum Tubingen
- Universitatsklinikum Ulm
- Universitatsklinikum Wurzburg
- Instituto Di Ematologia "L.Ea. Seragnoli"
- Unita Trapianti di Midollo Osseo per Adulti
- Presidio Ospedaliero "A. Businco" - Centro di Riferimento Oncologico Regionale
- Azienda Ospedaliera-Universitaria Vittorio Emanuele-Ferrarotto
- Azienda Ospedaliera Universitaria San Martino
- Farmacia Ospidaliera
- Ospedale Civile S. Maria delle Croci
- Ospedale Sant Eugenio
- Universita Degli Studi di Roma Tor Vergata
- Azienda Ospedaliero Universitaria Senese
- Azienda Ospedaliero Universitaria S. Maria della Misericordia di Udine, Clinica Ematologica
- University Medical Center Groningen
- Utrecht University Medical Centre, Dept. of Hematology
- Dolnoslaskie Centrum Transplantacji Komorkowych z
- Clinica Universidad de Navarra
- Hospital Clinic i Provincial de Barcelona
- Hospital de la Santa Creu i Sant Pau
- Institut Catala d'Oncologia del Hospital Universitari Germans
- Instituto Catalan de Oncologia-Hospital Universitari de Girona
- Hospital de la Princesa, Servicio de Hematologia
- Hospital General Universitario Gregorio Maranon
- Hospital Universitario de Salamanca, Hospital Clinico, Servicio de Hematologia
- Hospital La Fe, Servicio de Hematologia
- Addenbrook's Hospital
- Castle Hill Hospital
- Saint James University Hospital, Institute of Oncology
- Hanmmersmith Hospital, Dept. of Hematology
- Nottingham University Hospitals NHS Trust
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Cohort 1; ≥60 years of age
Cohort 2; ≥18 years of age
Participants ≥60 years of age who were relapsed after one first-line chemotherapy regimen (with or without consolidation) and after first complete remission <12 months or are primary refractory to first-line chemotherapy received a starting dose of 200 mg/day quizartinib. Exploratory: FLT3-ITD (+) and FLT3-ITD (-) Confirmatory: FLT3-ITD (+) and FLT3-ITD (-) After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.
Participants ≥18 years of age (including participants ≥60 years of age) who were relapsed or refractory after one second-line (salvage) regimen or after hematopoietic stem cell transplant (HSCT) received a starting dose of 200 mg/day quizartinib. Exploratory: FLT3-ITD (+) and FLT3-ITD (-) Confirmatory: FLT3-ITD (+) and FLT3-ITD (-) After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.