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

NCT ID: NCT00989261

Last Updated: 2019-12-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 333 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2014-12-31

Brief Summary

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).

Conditions

Acute Myeloid Leukemia

Keywords

AML; AC220; acute; FLT3; inhibitor; kinase; leukemia; leukaemia; myeloid; relapsed; refractory

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1; ≥60 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.

Group Type: EXPERIMENTAL

Compound AC220

Intervention Type: DRUG

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.

Cohort 2; ≥18 years of age

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.

Group Type: EXPERIMENTAL

Compound AC220

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

AC010220 × 2HCl, oral powder for reconstitution

Eligibility Criteria

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. Eastern Cooperative Oncology Group 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 × upper limit of normal (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 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.

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Interim Chief Medical Officer

Role: STUDY_DIRECTOR

Ambit Biosciences Corporation

Locations

University of California, San Francisco

San Francisco, California, United States

Northwestern Memorial Hospital

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

Indiana University

Indianapolis, Indiana, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

University of Maryland

Baltimore, Maryland, United States

Johns Hopkins Hospital

Baltimore, Maryland, United States

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Columbia University

New York, New York, United States

Oregon Health and Science University

Portland, Oregon, United States

Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Clinical Trials Center

Nashville, Tennessee, United States

The Vanderbuilt Clinic

Nashville, Tennessee, United States

M.D. Anderson Cancer Center

Houston, Texas, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Princess Margaret Hospital

Toronto, Ontario, Canada

Institut Paoli Calmettes Centre Regional de Lutte Contre le Cancer

Marseille, Cedex 9, France

Hematologie - CHU Purpan

Toulouse, Cedex, 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-Antoine

Paris, , France

Hopital Saint-Louis

Paris, , France

Hopital Haut-Leveque

Pessac, , France

Centre Henry Becquerel, Service d'Hematologie

Rouen, , France

Centre Hospitalier Regional Universitaire, Hopital de Hautepierre

Strasbourg, , France

Centre Hospitalier Universitaire Brabois

Vandœuvre-lès-Nancy, , France

Charite Campus Virchow Klinikum

Berlin, , Germany

Charite, Campus Benjamin Franklin

Berlin, , Germany

Universitatsklinikum Bonn

Bonn, , Germany

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

Hanover, , 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

München, , Germany

Universitatsklinikum Munster

Münster, , Germany

Universitatsklinikum Regensburg Abteilung fur Hamatologie

Regensburg, , Germany

Robert-Bosch-Krankenhaus GmbH

Stuttgart, , Germany

Universitatsklinikum Tubingen

Tübingen, , Germany

Universitatsklinikum Ulm

Ulm, , Germany

Universitatsklinikum Wurzburg

Würzburg, , Germany

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

Ospedale Sant Eugenio

Roma, , Italy

Universita Degli Studi di Roma Tor Vergata

Roma, , Italy

Azienda Ospedaliero Universitaria Senese

Siena, , Italy

Azienda Ospedaliero Universitaria S. Maria della Misericordia di Udine, Clinica Ematologica

Udine, , Italy

University Medical Center Groningen

Groningen, , Netherlands

Utrecht University Medical Centre, Dept. of Hematology

Utrecht, , Netherlands

Dolnoslaskie Centrum Transplantacji Komorkowych z

Wroclaw, , Poland

Clinica Universidad de Navarra

Pamplona, Navarre, Spain

Hospital Clinic i Provincial de Barcelona

Barcelona, , Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Institut Catala d'Oncologia del Hospital Universitari Germans

Barcelona, , Spain

Instituto Catalan de Oncologia-Hospital Universitari de Girona

Girona, , Spain

Hospital de la Princesa, Servicio de Hematologia

Madrid, , Spain

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Hospital Universitario de Salamanca, Hospital Clinico, Servicio de Hematologia

Salamanca, , Spain

Hospital La Fe, Servicio de Hematologia

Valencia, , Spain

Addenbrook's Hospital

Cambridge, , United Kingdom

Castle Hill Hospital

Cottingham, , United Kingdom

Saint James University Hospital, Institute of Oncology

Leeds, , United Kingdom

Hanmmersmith Hospital, Dept. of Hematology

London, , United Kingdom

Nottingham University Hospitals NHS Trust

Nottingham, , United Kingdom

Countries

United States; Canada; France; Germany; Italy; Netherlands; Poland; Spain; United Kingdom

References

Cortes J, Perl AE, Dohner H, Kantarjian H, Martinelli G, Kovacsovics T, Rousselot P, Steffen B, Dombret H, Estey E, Strickland S, Altman JK, Baldus CD, Burnett A, Kramer A, Russell N, Shah NP, Smith CC, Wang ES, Ifrah N, Gammon G, Trone D, Lazzaretto D, Levis M. Quizartinib, an FLT3 inhibitor, as monotherapy in patients with relapsed or refractory acute myeloid leukaemia: an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 2018 Jul;19(7):889-903. doi: 10.1016/S1470-2045(18)30240-7. Epub 2018 May 31.

Reference Type: DERIVED

PMID: 29859851 (View on PubMed)

Other Identifiers

2009-013093-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AC220-002

Identifier Type: -

Identifier Source: org_study_id