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

NCT00989261 | Completed Phase 2 Results DMC

• 2 other identifiers: AC220-0022009-013093-41
• Study Type: interventional
• Target: 333
• Locations: 9 countries
• Sites: 85

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

Outcome Measures

Primary Outcomes (3)

• Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants)

  Derived disease assessment based on local morphology of bone marrow disease performed by each local site pathologist, including all on-treatment data (Safety Population, FLT3-ITD\[+\] Participants) Modified from Cheson et al, abbreviations include the following: CR=complete remission; CRc=composite complete remission (CR+CRp+CRi); CRi=complete remission with incomplete hematological recovery, includes participants who met CRia criteria plus participants who met CRib criteria; CRia=all criteria specified for CR are met except for incomplete hematological recovery with residual neutropenia \<1 x 10\^9/L with or without complete platelet recovery. Red blood cell and platelet transfusion independence is not required; CRib=All criteria for CR or CRp are met, except for recent red blood cell or platelet transfusion; CRp=complete remission with incomplete platelet recovery; NR=no response; PR=partial remission.

  Within the first 3 cycles of treatment (84 days)

• Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants)

  Derived disease assessment based on local morphology of bone marrow disease performed by each local site pathologist, including all on-treatment data (Safety Population, FLT3-ITD\[-\] Participants) Modified from Cheson et al, abbreviations include the following: CR=complete remission; CRc=composite complete remission (CR+CRp+CRi); CRi=complete remission with incomplete hematological recovery, includes participants who met CRia criteria plus participants who met CRib criteria; CRia=all criteria specified for CR are met except for incomplete hematological recovery with residual neutropenia \<1 x 10\^9/L with or without complete platelet recovery. Red blood cell and platelet transfusion independence is not required; CRib=All criteria for CR or CRp are met, except for recent red blood cell or platelet transfusion; CRp=complete remission with incomplete platelet recovery; NR=no response; PR=partial remission.

  Within the first 3 cycles of treatment (84 days)

• Number of Participants With Composite Complete Remission (CRc), Categorised by FLT3-ITD Status

  CRc is defined as composite complete remission (CR+CRp+CRi) - CR = complete remission; CRp = complete remission with incomplete platelet recovery; CRi = complete remission with incomplete hematological recovery, includes participants who met CRia criteria plus participants who met CRib criteria; CRia = all criteria specified for CR are met except for incomplete hematological recovery with residual neutropenia \<1 x 10\^9/L with or without complete platelet recovery. Red blood cell and platelet transfusion independence is not required; CRib = all criteria for CR or CRp are met, except for recent red blood cell or platelet transfusion.

  within 28 months

Secondary Outcomes (9)

• Duration of Composite Complete Remission in FLT3-ITD (+) Participants Who Achieved CRc Based on All On-Treatment Data

  From time at which CRc was achieved until disease progression or death, up to approximately 3 years post treatment

• Duration of Composite Complete Remission in FLT3-ITD (-) Participants Who Achieved CRc Based on All On-Treatment Data

  From time at which CRc was achieved until disease progression or death, up to approximately 3 years post treatment

• Duration of Any Response in FLT3-ITD (+) Participants

  From the time of any response until disease progression or death, up to approximately 3 years post treatment

• Duration of Any Response in FLT3-ITD (-) Participants

  From the time of any response until disease progression or death, up to approximately 3 years post treatment

• Median Duration of Leukemia-free Survival in FLT3-ITD (+) Participants

  From the time CRc was achieved until disease progression or death, up to approximately 3 years post treatment

Study Arms (2)

Cohort 1; ≥60 years of age

EXPERIMENTAL

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.

Drug: Compound AC220

Cohort 2; ≥18 years of age

EXPERIMENTAL

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.

Drug: Compound AC220

Interventions

Compound AC220 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.

Also known as: AC010220 × 2HCl, oral powder for reconstitution

Cohort 1; ≥60 years of age; Cohort 2; ≥18 years of age

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (85)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21231, United States

Location

University of Michigan Medical Center

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Clinical Trials Center

Nashville, Tennessee, 37212, United States

Location

The Vanderbuilt Clinic

Nashville, Tennessee, 37232, United States

Location

M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Institut Paoli Calmettes Centre Regional de Lutte Contre le Cancer

Marseille, Cedex 9, France

Location

Hematologie - CHU Purpan

Toulouse, Cedex, France

Location

Hopital Avicenne

Bobigny, France

Location

Centre Hospitalier Universitaire d'Angers

d'Angers, France

Location

Centre Hospitalier Universitaire Grenoble

Grenoble, France

Location

Centre Hospitalier de Versailles

Le Chesnay, France

Location

Hopital Claude Huriez

Lille, France

Location

Centre Hospitalier Universitaire Limoges

Limoges, France

Location

Hopital Edouard Herriot

Lyon, France

Location

Hopital Saint-Antoine

Paris, France

Location

Hopital Saint-Louis

Paris, France

Location

Hopital Haut-Leveque

Pessac, France

Location

Centre Henry Becquerel, Service d'Hematologie

Rouen, France

Location

Centre Hospitalier Regional Universitaire, Hopital de Hautepierre

Strasbourg, France

Location

Centre Hospitalier Universitaire Brabois

Vandœuvre-lès-Nancy, France

Location

Charite Campus Virchow Klinikum

Berlin, Germany

Location

Charite, Campus Benjamin Franklin

Berlin, Germany

Location

Universitatsklinikum Bonn

Bonn, 5311, Germany

Location

Unikliniksklinikum Carl Gustav Carus

Dresden, Germany

Location

Uniklinik Essen, Westdeutsches Tumorzentrum

Essen, Germany

Location

Klinikum der Johann Wolfgang Goethe Universitat

Frankfurt am Main, Germany

Location

Asklepios Klinik St Georg

Hamburg, Germany

Location

Medizinische Hochschule Hannover

Hanover, Germany

Location

Universitatsklinikum Heidelberg

Heidelberg, Germany

Location

Universitatsklinikum Jena

Jena, Germany

Location

Universitatsklinikum Leipzig Selbstandige Abteilung fur Hamatologie

Leipzig, Germany

Location

Universitatsklinikum Magdeburg

Magdeburg, Germany

Location

Universitatsklinikum Mannheim

Mannheim, Germany

Location

Philipps-Universitat Marburg

Marburg, Germany

Location

Klinikum rechts der Isar, Technische Universitat Munchen

München, Germany

Location

Universitatsklinikum Munster

Münster, Germany

Location

Universitatsklinikum Regensburg Abteilung fur Hamatologie

Regensburg, Germany

Location

Robert-Bosch-Krankenhaus GmbH

Stuttgart, Germany

Location

Universitatsklinikum Tubingen

Tübingen, Germany

Location

Universitatsklinikum Ulm

Ulm, Germany

Location

Universitatsklinikum Wurzburg

Würzburg, Germany

Location

Instituto Di Ematologia "L.Ea. Seragnoli"

Bologna, Italy

Location

Unita Trapianti di Midollo Osseo per Adulti

Brescia, Italy

Location

Presidio Ospedaliero "A. Businco" - Centro di Riferimento Oncologico Regionale

Cagliari, Italy

Location

Azienda Ospedaliera-Universitaria Vittorio Emanuele-Ferrarotto

Catania, Italy

Location

Azienda Ospedaliera Universitaria San Martino

Genova, Italy

Location

Farmacia Ospidaliera

Orbassano, Italy

Location

Ospedale Civile S. Maria delle Croci

Ravenna, 48100, Italy

Location

Ospedale Sant Eugenio

Roma, 00144, Italy

Location

Universita Degli Studi di Roma Tor Vergata

Roma, Italy

Location

Azienda Ospedaliero Universitaria Senese

Siena, Italy

Location

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

Udine, Italy

Location

University Medical Center Groningen

Groningen, Netherlands

Location

Utrecht University Medical Centre, Dept. of Hematology

Utrecht, Netherlands

Location

Dolnoslaskie Centrum Transplantacji Komorkowych z

Wroclaw, Poland

Location

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Institut Catala d'Oncologia del Hospital Universitari Germans

Barcelona, Spain

Location

Instituto Catalan de Oncologia-Hospital Universitari de Girona

Girona, Spain

Location

Hospital de la Princesa, Servicio de Hematologia

Madrid, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, Spain

Location

Hospital Universitario de Salamanca, Hospital Clinico, Servicio de Hematologia

Salamanca, Spain

Location

Hospital La Fe, Servicio de Hematologia

Valencia, Spain

Location

Addenbrook's Hospital

Cambridge, United Kingdom

Location

Castle Hill Hospital

Cottingham, HU 16 5JQ, United Kingdom

Location

Saint James University Hospital, Institute of Oncology

Leeds, LS9 7TF, United Kingdom

Location

Hanmmersmith Hospital, Dept. of Hematology

London, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, NG5 1PB, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 29859851 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia; Recurrence

Interventions

quizartinib; Powders

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Daiichi Sankyo
• Organization: Contact for Clinical Trial Information

CTRinfo@dsi.com

1-908-992-6400

Study Officials

• Interim Chief Medical Officer

  Ambit Biosciences Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2009
• First Posted: October 5, 2009
• Study Start: November 1, 2009
• Primary Completion: September 28, 2012
• Study Completion: December 31, 2014
• Last Updated: December 11, 2019
• Results First Posted: November 29, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

IT (11); PL (1); FR (15); DE (21); US (20); NL (2); ES (9); GB (5); CA (1)