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Acute Myeloid LeukemiaPhase 2ACENCT00989261

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

A Phase 2 study testing Compound AC220 in people with Acute Myeloid Leukemia, run by Daiichi Sankyo at 85 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Compound AC220
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
333 participants
Where
85 sitesin 9 countries
Study dates
Nov 2009to 31 Dec 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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
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  • 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

Trial locations and contacts

85 sites in 9 countries.

85 sites in 9 countries

Germany21 sites

  • Charite Campus Virchow Klinikum

    Berlin

  • Charite, Campus Benjamin Franklin

    Berlin

  • Universitatsklinikum Bonn

    Bonn, 5311

  • Unikliniksklinikum Carl Gustav Carus

    Dresden

  • Uniklinik Essen, Westdeutsches Tumorzentrum

    Essen

  • Klinikum der Johann Wolfgang Goethe Universitat

    Frankfurt am Main

  • Asklepios Klinik St Georg

    Hamburg

  • Medizinische Hochschule Hannover

    Hanover

  • Universitatsklinikum Heidelberg

    Heidelberg

  • Universitatsklinikum Jena

    Jena

  • Universitatsklinikum Leipzig Selbstandige Abteilung fur Hamatologie

    Leipzig

  • Universitatsklinikum Magdeburg

    Magdeburg

  • Universitatsklinikum Mannheim

    Mannheim

  • Philipps-Universitat Marburg

    Marburg

  • Klinikum rechts der Isar, Technische Universitat Munchen

    München

  • Universitatsklinikum Munster

    Münster

  • Universitatsklinikum Regensburg Abteilung fur Hamatologie

    Regensburg

  • Robert-Bosch-Krankenhaus GmbH

    Stuttgart

  • Universitatsklinikum Tubingen

    Tübingen

  • Universitatsklinikum Ulm

    Ulm

  • Universitatsklinikum Wurzburg

    Würzburg

Other trials in Germany

United States20 sites

  • University of Michigan Medical Center

    Ann Arbor, Michigan, 48109

  • University of Maryland

    Baltimore, Maryland, 21201

  • Johns Hopkins Hospital

    Baltimore, Maryland, 21231

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Northwestern Memorial Hospital

    Chicago, Illinois, 60611

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • M.D. Anderson Cancer Center

    Houston, Texas, 77030

  • Indiana University

    Indianapolis, Indiana, 46202

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Clinical Trials Center

    Nashville, Tennessee, 37212

  • The Vanderbuilt Clinic

    Nashville, Tennessee, 37232

  • Columbia University

    New York, New York, 10032

  • Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of California, San Francisco

    San Francisco, California, 94143

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

Other trials in United States

France15 sites

  • Hopital Avicenne

    Bobigny

  • Centre Hospitalier Universitaire d'Angers

    d'Angers

  • Centre Hospitalier Universitaire Grenoble

    Grenoble

  • Centre Hospitalier de Versailles

    Le Chesnay

  • Hopital Claude Huriez

    Lille

  • Centre Hospitalier Universitaire Limoges

    Limoges

  • Hopital Edouard Herriot

    Lyon

  • Institut Paoli Calmettes Centre Regional de Lutte Contre le Cancer

    Marseille, Cedex 9

  • Hopital Saint-Antoine

    Paris

  • Hopital Saint-Louis

    Paris

  • Hopital Haut-Leveque

    Pessac

  • Centre Henry Becquerel, Service d'Hematologie

    Rouen

  • Centre Hospitalier Regional Universitaire, Hopital de Hautepierre

    Strasbourg

  • Hematologie - CHU Purpan

    Toulouse, Cedex

  • Centre Hospitalier Universitaire Brabois

    Vandœuvre-lès-Nancy

Other trials in France

Italy11 sites

  • Instituto Di Ematologia "L.Ea. Seragnoli"

    Bologna

  • Unita Trapianti di Midollo Osseo per Adulti

    Brescia

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

    Cagliari

  • Azienda Ospedaliera-Universitaria Vittorio Emanuele-Ferrarotto

    Catania

  • Azienda Ospedaliera Universitaria San Martino

    Genova

  • Farmacia Ospidaliera

    Orbassano

  • Ospedale Civile S. Maria delle Croci

    Ravenna, 48100

  • Ospedale Sant Eugenio

    Roma, 00144

  • Universita Degli Studi di Roma Tor Vergata

    Roma

  • Azienda Ospedaliero Universitaria Senese

    Siena

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

    Udine

Other trials in Italy

Spain9 sites

  • Hospital Clinic i Provincial de Barcelona

    Barcelona

  • Hospital de la Santa Creu i Sant Pau

    Barcelona

  • Institut Catala d'Oncologia del Hospital Universitari Germans

    Barcelona

  • Instituto Catalan de Oncologia-Hospital Universitari de Girona

    Girona

  • Hospital de la Princesa, Servicio de Hematologia

    Madrid

  • Hospital General Universitario Gregorio Maranon

    Madrid

  • Clinica Universidad de Navarra

    Pamplona, Navarre, 31008

  • Hospital Universitario de Salamanca, Hospital Clinico, Servicio de Hematologia

    Salamanca

  • Hospital La Fe, Servicio de Hematologia

    Valencia

Other trials in Spain

United Kingdom5 sites

  • Addenbrook's Hospital

    Cambridge

  • Castle Hill Hospital

    Cottingham, HU 16 5JQ

  • Saint James University Hospital, Institute of Oncology

    Leeds, LS9 7TF

  • Hanmmersmith Hospital, Dept. of Hematology

    London

  • Nottingham University Hospitals NHS Trust

    Nottingham, NG5 1PB

Other trials in United Kingdom

Netherlands2 sites

  • University Medical Center Groningen

    Groningen

  • Utrecht University Medical Centre, Dept. of Hematology

    Utrecht

Other trials in Netherlands

Canada1 site

  • Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

Poland1 site

  • Dolnoslaskie Centrum Transplantacji Komorkowych z

    Wroclaw

Other trials in Poland

About this study

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

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).

Being tested
Compound AC220
Keywords
AML, AC220, acute, FLT3, inhibitor, kinase, leukemia, leukaemia, myeloid, relapsed, refractory
Medical subject headings
Leukemia, Myeloid, Acute, Leukemia, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Compound AC220Drug

    Also called AC010220 × 2HCl, oral powder for reconstitution

    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.

Study groups in NCT00989261
Study groupRoleWhat they receive
Cohort 1; ≥60 years of ageExperimentalParticipants ≥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.
Receives: Drug: Compound AC220
Cohort 2; ≥18 years of ageExperimentalParticipants ≥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.
Receives: Drug: Compound AC220

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Within the first 3 cycles of treatment (84 days)

  2. 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.

    Measured: Within the first 3 cycles of treatment (84 days)

  3. 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.

    Measured: within 28 months

Secondary outcomes (9)

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

    Kaplan-Meier analysis of duration of composite complete remission derived based on local morphology including all on-treatment data (Safety Population).

    The definition of relapse at CRc includes an evaluation of blasts in the peripheral blood of >1%.Though not specified in the protocol, the addition of these criteria was deemed necessary for consistency with the Cheson criteria.

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

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

    Kaplan-Meier analysis of duration of composite complete remission derived based on local morphology including all on-treatment data (Safety Population).

    The definition of relapse at CRc includes an evaluation of blasts in the peripheral blood of >1%.Though not specified in the protocol, the addition of these criteria was deemed necessary for consistency with the Cheson criteria.

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

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

    Kaplan-Meier analysis of duration of any response (CR, CRp, CRi, or PR), derived based on local morphology for participants who achieved a response during the first 3 cycles of treatment (Safety Population).

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

  4. Duration of Any Response in FLT3-ITD (-) Participants

    Kaplan-Meier analysis of duration of any response (CR, CRp, CRi, or PR), derived based on local morphology for participants who achieved a response during the first 3 cycles of treatment (Safety Population).

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

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

    Kaplan-Meier analysis of leukemia-free survival in participants who achieved a CRc in the first three cycles of treatment derived based on local morphology (Safety Population).

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

  6. Median Duration of Leukemia-free Survival in FLT3-ITD (-) Participants

    Kaplan-Meier analysis of leukemia-free survival in participants who achieved a CRc in the first three cycles of treatment derived based on local morphology (Safety Population).

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

  7. Median Duration of Overall Survival in FLT3-ITD (+) Participants

    Kaplan-Meier analysis of overall survival (Safety Population)

    Measured: Time from first dose to death from any cause, up to 3 years post treatment

  8. Median Duration of Overall Survival in FLT3-ITD (-) Participants

    Kaplan-Meier analysis of overall survival (Safety Population)

    Measured: Time from first dose to death from any cause, up to approximately 3 years post treatment

  9. Early Treatment-related Death

    Early treatment-related deaths included all treatment-related deaths prior to the end of Cycle 3 with a 3-day window (Cycle 3 end date + 3 days), unless the death was following a CRc response assessed by the Investigator.

    Measured: Within first 3 cycles of treatment (84 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Oct 2009 (estimated)
  2. Study startNov 2009
  3. Primary completion28 Sep 2012
  4. Study completion31 Dec 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
333 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00989261
Sponsor's protocol ID
AC220-002
Other IDs
2009-013093-41, 2009
Acronym
ACE
Status last verified
Dec 2019
First submitted
1 Oct 2009
Last updated
11 Dec 2019
Data monitoring committee
Yes
Individual data sharing
Yes: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Publications

  • 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.

    PubMed 29859851

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Compound AC220 in people with Acute Myeloid Leukemia, run by Daiichi Sankyo at 85 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 85 sites in Germany, United States, France, Italy, Spain and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants) (time frame: Within the first 3 cycles of treatment (84 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00989261, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2019.

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