AMLPhase 3NCT02039726
(QuANTUM-R): An Open-label Study of Quizartinib Monotherapy vs. Salvage Chemotherapy in Acute Myeloid Leukemia (AML) Subjects Who Are FLT3-ITD Positive
A Phase 3 study testing Quizartinib and Salvage Chemotherapy in people with AML, run by Daiichi Sankyo at 131 sites in 19 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- AML
- What is being tested?
- Quizartinib and Salvage Chemotherapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 367 participants
- Where
- 131 sitesin 19 countries
- Study dates
- May 2014to 8 Sep 2020
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Age ≥ 18 years or the minimum legal adult age (whichever is greater) at the time of Informed consent.
- 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.
- In first relapse (with duration of remission of 6 months or less) or refractory after prior therapy, with or without HSCT. Induction therapy must have included at least 1 cycle of an anthracycline/mitoxantrone-containing induction block at a standard dose.
- 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). If a specimen has been sent for FLT3-ITD testing at the central laboratory but the subject requires treatment for AML before the central FLT3-ITD test result is available, a local test result may be acceptable for randomization after consultation with the Medical Monitor.
- Eligibility for pre-selected salvage chemotherapy, according to the Investigator's assessment.
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- Eastern Cooperative Oncology Group (ECOG) performance score 0-2.
- Discontinuation of prior AML treatment before the start of study treatment (except hydroxyurea or other treatment to control leukocytosis) for at least 2 weeks for cytotoxic agents, or for at least 5 half-lives for non cytotoxic agents.
- Serum creatinine ≤1.5×upper limit of normal (ULN), or glomerular filtration rate >25 mL/min, as calculated with the Cockcroft-Gault formula.
- 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.
- Total serum bilirubin ≤1.5×ULN.
- Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤2.5×ULN.
Who cannot join
- Acute Promyelocytic Leukemia (AML subtype M3).
- AML secondary to prior chemotherapy for other neoplasms, except AML secondary to prior Myelodysplastic Syndrome (MDS).
- History of another malignancy, unless the candidate has been disease-free for at least 5 years.
- Persistent, clinically significant > Grade 1 non-hematologic toxicity from prior AML therapy.
- 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.
- History of or current, central nervous system involvement with AML.
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- Clinically significant coagulation abnormality, such as disseminated intravascular coagulation.
- Prior treatment with quizartinib or participated in a prior quizartinib study.
- Prior treatment with a FLT3 targeted therapy including sorafenib or investigational FLT3 inhibitors (not including the multi-kinase inhibitor, midostaurin).
- Major surgery within 4 weeks prior to screening.
- Radiation therapy within 4 weeks prior to screening.
- Uncontrolled or significant cardiovascular disease
- Active infection not well controlled by antibacterial or antiviral therapy.
- Known infection with human immunodeficiency virus, or active hepatitis B or C, or other active clinically relevant liver disease.
- Unwillingness to receive infusion of blood products according to the protocol.
- In a man whose sexual partner is a woman of childbearing potential, unwillingness or inability of the man or woman to use a highly effective contraceptive method for the entire study treatment period for at least 3 months after study completion. Male subjects must not freeze or donate sperm starting at Screening and throughout the study period, and 105 days after the final study drug administration.
- In a heterosexually active woman of childbearing potential, unwillingness or inability to use a highly effective contraceptive method for the entire study treatment period and for at least 3 months after study treatment completion. Additionally, for women randomized to chemotherapy, unwillingness to adhere to the restrictions in the respective locally established guidelines and local approved label (prescribing information, Summary of Product Characteristics, or US product insert) from the manufacturer and the Patient Information Leaflet (package insert) as instructed by the Investigator.
- Pregnancy.
- Female Subjects must agree to not breastfeed from the time of Screening and throughout the study period, and for 25 days after the final study drug administration.
- 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.
- For subjects in the United Kingdom only: Refusal of permission to allow the subject's General Practitioner to be notified of their participation in the study.
Trial locations and contacts
131 sites in 19 countries.
131 sites in 19 countries
United States36 sites
University of Michigan Health System
Ann Arbor, Michigan, 48109
Emory Winship Cancer Institute
Atlanta, Georgia, 30322
University of Maryland
Baltimore, Maryland, 21201
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Roswell Park Cancer Institute
Buffalo, New York, 14263
UNC Linebreger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
University of Illinois at Chicago
Chicago, Illinois, 60607
University of Chicago
Chicago, Illinois, 60637
University of Cincinnati
Cincinnati, Ohio, 45267
Geisinger Medical Center
Danville, Pennsylvania, 17822
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201
City of Hope National Medical Center
Duarte, California, 91010
Duke Cancer Institute at Duke University Health System
Durham, North Carolina, 27710
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033
MD Anderson Center, The University of Texas
Houston, Texas, 77030
Franciscan Alliance
Indianapolis, Indiana, 46237
University of Southern California, Norris Comprehensive Cancer Center
Los Angeles, California, 90033
UCLA Medical Center
Los Angeles, California, 90095
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
Yale University
New Haven, Connecticut, 06520
Columbia University Medical Center
New York, New York, 10032
University of Nebraska Medical Center
Omaha, Nebraska, 68198
University of Pennsylvania Health System
Philadelphia, Pennsylvania, 19104
Oregon Health and Science University Knight Cancer Institute
Portland, Oregon, 97239
Mayo Clinic
Rochester, Minnesota, 55905
University of Rochester
Rochester, New York, 14642
UC Davis Cancer Center
Sacramento, California, 95817
Swedish Cancer Institute
Seattle, Washington, 98104
LSU Health Sciences Center Feist Weiller Cancer Center
Shreveport, Louisiana, 71103
Avera Cancer Institute
Sioux Falls, South Dakota, 57105
Washington University School of Medicine
St Louis, Missouri, 63110
Stanford University Medical Center Stanford Comprehensive Cancer Center
Stanford, California, 94305
NY Medical College
Valhalla, New York, 10595
University of Kansas Medical Center Research Institute Inc
Westwood, Kansas, 66205
Wake Forest University Baptist Health
Winston-Salem, North Carolina, 27157
Germany14 sites
Charité Universitätsmedizin Berlin
Berlin, 12200
Charité Campus Virchow Klinikum
Berlin, 13353
Klinikum Braunschweig
Braunschweig, 38114
Universitatsklinikum Dresden
Dresden, 01307
Klinikum der Johann Wolfgang-Goethe-Universität
Frankfurt, 60590
Universitätsklinikum Halle
Halle, 06120
Medizinische Hochschule Hannover
Hanover, 30625
Uniklinik Heidelberg Medizinische Klinik und Poliklinik V
Heidelberg, 69120
Universitätsklinikum Jena
Jena, 07743
Universitätsklinikum Leipzig
Leipzig, 04103
University Mainz
Mainz, 55131
Universitätsklinikum Giessen und Marburg GmbH
Marburg, 35043
LMU München Klinikum Großhadern
München, 81377
Medizinische Klinik A Hämatologie Hämostaseologie Internistische Onkologie und Pneumologie
Münster, 48149
Italy14 sites
AOU Policlinico Consorziale di Bari
Bari, 70124
Università di Bologna
Bologna, 40138
Unità Operativa di Ematologia e Unità Operativa CTMO
Cagliari
Arcispedale S Anna
Ferrara, 44124
AOU Careggi
Florence, 50134
IRCCS Azienda Ospedaliera Universitaria San Martino
Genova, 16132
Opsedale San Martino di Genova
Genova, 16132
Ospedale San Raffaele
Milan, 20132
Azienda Ospedaliera Universitaria Federico II
Naples, 80131
Azienda Ospedaliero Universitaria San Luigi Gonzaga
Orbassano, 10043
L'UOC di Ematologia del Policlinico Tor Vergata
Rome, 00133
Policlinico Universitario Agostino Gemelli
Rome, 00168
Azienda Ospedaliero Universitaria Senese, Policlinico S. Maria alle Scotte
Siena, 53100
Ospedale di Circolo-a Fondazione Macchi
Varese, 21100
France10 sites
CHU de Caen
Caen, 14000
Centre Hospitalier Universitaire Grenoble Hopital Michalon
Grenoble, 38043
Centre Hospitalier de Versailles
Le Chesnay, 78157
Hopital de la Conception
Marseille, 13385
Centre Hospitalier Universitaire Nantes
Nantes, 44035
Hôpital Saint Louis
Paris, 75010
Hopital Saint-Antoine
Paris, 75571
Hopital Haut Leveque Centre Francois Magendie
Pessac, 33604
Centre Henri-Becquerel
Rouen, 76038
Centre Hospitalier Universitaire Purpan
Toulouse, 31059
Spain8 sites
Hospital Clinic I Provincial de Barcelona
Barcelona, 08036
Hospital Universitari Germans Trias i Pujol
Barcelona, 08916
Hospital General Universitario Gregorio Marañon
Madrid, 28007
Hospital Son Espases
Palma, De Mallorca, 07120
Complejo Hospitalario de Navarra
Pamplona, 31008
Hospital Clínico Universitario de Salamanca
Salamanca, 37007
Hospital Universitario Virgen del Rocio
Seville, 41013
Hospital La Fe
Valencia, SP, 46026
United Kingdom7 sites
Aberdeen Royal Infirmary
Aberdeen, Scotland, AB25 2ZN
Bristol Haematology and Oncology Centre
Bristol, England, BS2 8ED
University Hospital of Wales
Cardiff, South Glamorgan, CF14 4XW
Saint James University Hospital
Leeds, England, LS9 7TF
King's College Hospital
London, England, SE5 9RS
Nottingham City Hospital NHS Trust
Nottingham, England, NG51PB
Royal Marsden Hospital Sutton
Sutton, England, SM2 5PT
Australia6 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
The Princess Alexandra Hospital
Brisbane, Queensland
The Canbera Hospital
Garran, New South Wales, 2605
Alfred Hospital
Melbourne, Victoria, 3004
Westmead Hospital
Westmead, New South Wales, 2145
The Queen Elizabeth Hospital
Woodville, South Australia, 5011
South Korea6 sites
Kyungpook National University Hospital
Daegu, 700-721
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 463-707
Seoul National University Hospital
Seoul, 110-744
Samsung Medical Center
Seoul, 135-710
The Catholic University of Korea Seoul St. Mary's Hospital
Seoul, 137-701
Asan Medical Center
Seoul, 138-736
Taiwan4 sites
China Medical University Hospital
Taichung, 404
National Cheng Kung University Hospital
Tainan, 704
National Taiwan University Hospital
Taipei, 100
Taipei Veterans General Hospital
Taipei, 112
Belgium3 sites
ZNA Stuivenberg
Antwerp, BE, 2060
UCL St Luc
Brussels, BE, 1200
Leuven UZ Gasthuisberg
Leuven, BE, 3000
Canada3 sites
University of Alberta Hospital
Edmonton, Alberta, T6G 2B7
Princess Margaret Cancer Centre Princess Margaret Hospital
Toronto, Ontario, M5G2M9
Vancouver General Hospital
Vancouver, British Columbia, V5Z 1M9
Czechia3 sites
Fakultni nemocnice Brno
Brno, 62500
Fakultni nemocnice Hradec Kralove
Hradec Králové, 50005
Fakultni nemocnice Olomouc
Olomouc, 77900
Hungary3 sites
Semmelweis Egyetem Altalanos Orvostudomanyi Kar I. Belgyogyaszati Klinika
Budapest, Pest County, 1083
Debreceni Egyetem Klinikai Kozpont, Belgyogyaszati Intezet
Debrecen, Hajdú-Bihar, 4032
Szegedi Tudomanyegyetem Altalanos Orvostudomanyi Kar Szent Gyorgyi Albert Klinikai Kozpont
Szeged, Csongrád megye, 6725
Netherlands3 sites
VU Medisch Centrum
Amsterdam, 1081 HV
Universitair Medisch Centrum Groningen
Groningen, 9713 GZ
Erasmus Medical Center
Rotterdam, 3015 CE
Poland3 sites
Uniwersytecki Szpital Kliniczny w Biatymstoku, Klinika Hematologii z Pododzialem Chorob Naczyn
Bialystok, 15276
Samodzielny Publiczny Szpital Kliniczny im. Andrzeja Mieleckiego Slaskiego Uniwersytetu Medycznego w Katowicach Oddzial Hematologii i Transplantacji Szpiku
Katowice, 40032
Samodzielny Publiczny Szpital Kliniczny Nr 1, Klinika Hematoonkologii i Transplantacji Szpiku
Lublin, 20081
Croatia2 sites
Klinička Bolinca Merkur
Zagreb, 10000
Kliničko Bolnički Centar Zagreb
Zagreb, 10000
Hong Kong2 sites
The Chinese University of Hong Kong, Prince of Wales Hospital
Hong Kong
The University of Hong Kong, Queen Mary Hospital
Hong Kong
Serbia2 sites
Klinicki Centar Srbije
Belgrade, 11000
Klinicki Centar Vojvodine
Novi Sad, 21000
Singapore2 sites
National University of Singapore
Singapore, 119228
Singapore General Hospital
Singapore, 169608
About this study
Official title: A Phase 3 Open-label Randomized Study of Quizartinib (AC220) Monotherapy Versus Salvage Chemotherapy in Subjects With Tyrosine Kinase 3 - Internal Tandem Duplication (FLT3-ITD) Positive Acute Myeloid Leukemia (AML) Refractory to or Relapsed After First-line Treatment With or Without Hematopoietic Stem Cell Transplantation (HSCT) Consolidation
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.
- Conditions
- AML
- Being tested
- Quizartinib, Salvage Chemotherapy
- Keywords
- Acute Myeloid Leukemia, AML, FMS-like tyrosine kinase 3, FLT3-ITD, Quizartinib, Leukemia, Tablets
- Medical subject headings
- Leukemia, Myeloid, Acute, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
QuizartinibDrug
Also called AC220
20 or 30 mg quizartinib tablets administered orally once daily
Salvage ChemotherapyDrug
Also called Standard of Care
Low dose cytarabine (LoDAC); mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC); or fludarabine, cytarabine, and granulocyte colony stimulating factor (G-CSF) with idarubicin (FLAG-IDA) administered during 28-day cycles
| Study group | Role | What they receive |
|---|---|---|
| Quizartinib | Experimental | Participants who were randomized to receive 20 or 30 mg quizartinib tablets administered orally once daily. Receives: Drug: Quizartinib |
| Salvage chemotherapy | Active comparator | Participants who were randomized to receive salvage chemotherapy, such as low dose cytarabine (LoDAC); mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC); or fludarabine, cytarabine, and granulocyte colony stimulating factor (G-CSF) with idarubicin (FLAG-IDA), were administered during 28-day cycles. Receives: Drug: Salvage Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival in Participants That Received Quizartinib Versus Salvage Chemotherapy
Overall Survival is defined as the time (in weeks) from the date of randomization to the date of death due to any cause. Median and quartiles are calculated using the Kaplan-Meier method.
Measured: At approximately 3 years 9 months
Secondary outcomes (1)
Event-free Survival in Participants That Received Quizartinib Versus Salvage Chemotherapy
Event-free survival is defined as the time (in weeks) from randomization until documented refractory disease, relapse after complete composite remission (CRc), or death from any cause, whichever is observed first.
Measured: At approximately 3 years 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2014 (estimated)
- Study startMay 2014
- Primary completion22 Feb 2018
- Study completion8 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for AMLStudies of the same condition, open and under way.
- More trials run by Daiichi SankyoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 367 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jorge E. Cortes, MD, Principal investigator, M.D. Anderson Cancer CenterGlobal Clinical Leader, Study director, Daiichi Sankyo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02039726
- Sponsor's protocol ID
- AC220-007
- Other IDs
- EudraCT Number 2013-004890-28
- Status last verified
- Feb 2021
- First submitted
- 15 Jan 2014
- Last updated
- 24 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- 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
Kang D, Ludwig E, Jaworowicz D, Huang H, Fiedler-Kelly J, Cortes J, Ganguly S, Khaled S, Kramer A, Levis M, Martinelli G, Perl A, Russell N, Abutarif M, Choi Y, Yin O. Concentration-QTc analysis of quizartinib in patients with relapsed/refractory acute myeloid leukemia. Cancer Chemother Pharmacol. 2021 Apr;87(4):513-523. doi: 10.1007/s00280-020-04204-y. Epub 2021 Jan 8.
PubMed 33415416Cortes JE, Khaled S, Martinelli G, Perl AE, Ganguly S, Russell N, Kramer A, Dombret H, Hogge D, Jonas BA, Leung AY, Mehta P, Montesinos P, Radsak M, Sica S, Arunachalam M, Holmes M, Kobayashi K, Namuyinga R, Ge N, Yver A, Zhang Y, Levis MJ. Quizartinib versus salvage chemotherapy in relapsed or refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): a multicentre, randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2019 Jul;20(7):984-997. doi: 10.1016/S1470-2045(19)30150-0. Epub 2019 Jun 4.
PubMed 31175001Cortes 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
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Open-label Randomized Study of Quizartinib (AC220) Monotherapy Versus Salvage Chemotherapy in Subjects With Tyrosine Kinase 3 - Internal Tandem Duplication (FLT3-ITD) Positive Acute Myeloid Leukemia (AML) Refractory to or Relapsed After First-line Treatment With or Without Hematopoietic Stem Cell Transplantation (HSCT) Consolidation
- ClinicalTrials.gov ID
- NCT02039726
- Acronym / sponsor ID
- AC220-007
- Conditions
- AML
- Keywords
- Acute Myeloid Leukemia, AML, FMS-like tyrosine kinase 3, FLT3-ITD, Quizartinib, Leukemia, Tablets
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 367 participants (actual)
- Lead sponsor
- Daiichi SankyoIndustry (pharma, biotech, devices)
- Study start
- May 2014 (actual)
- Primary completion
- 22 Feb 2018 (actual)
- Study completion
- 8 Sep 2020 (actual)
- First posted
- 20 Jan 2014 (estimated)
- Results
- Posted 27 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Quizartinib | Experimental | Drug: QuizartinibParticipants who were randomized to receive 20 or 30 mg quizartinib tablets administered orally once daily. |
| Salvage chemotherapy | Active comparator | Drug: Salvage ChemotherapyParticipants who were randomized to receive salvage chemotherapy, such as low dose cytarabine (LoDAC); mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC); or fludarabine, cytarabine, and granulocyte colony stimulating factor (G-CSF) with idarubicin (FLAG-IDA), were administered during 28-day cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
- Age ≥ 18 years or the minimum legal adult age (whichever is greater) at the time of Informed consent.
- 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.
- In first relapse (with duration of remission of 6 months or less) or refractory after prior therapy, with or without HSCT. Induction therapy must have included at least 1 cycle of an anthracycline/mitoxantrone-containing induction block at a standard dose.
- 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). If a specimen has been sent for FLT3-ITD testing at the central laboratory but the subject requires treatment for AML before the central FLT3-ITD test result is available, a local test result may be acceptable for randomization after consultation with the Medical Monitor.
Key exclusion criteria (21 listed)
- Acute Promyelocytic Leukemia (AML subtype M3).
- AML secondary to prior chemotherapy for other neoplasms, except AML secondary to prior Myelodysplastic Syndrome (MDS).
- History of another malignancy, unless the candidate has been disease-free for at least 5 years.
- Persistent, clinically significant > Grade 1 non-hematologic toxicity from prior AML therapy.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| QuizartinibAlso: AC22020 or 30 mg quizartinib tablets administered orally once daily | Drug | Quizartinib |
| Salvage ChemotherapyAlso: Standard of CareLow dose cytarabine (LoDAC); mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC); or fludarabine, cytarabine, and granulocyte colony stimulating factor (G-CSF) with idarubicin (FLAG-IDA) administered during 28-day cycles | Drug | Salvage chemotherapy |
Primary outcome
Overall Survival in Participants That Received Quizartinib Versus Salvage Chemotherapy
Time frame: At approximately 3 years 9 months
Overall Survival is defined as the time (in weeks) from the date of randomization to the date of death due to any cause. Median and quartiles are calculated using the Kaplan-Meier method.
1 secondary outcome
Event-free Survival in Participants That Received Quizartinib Versus Salvage Chemotherapy
Time frame: At approximately 3 years 9 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33415416Kang D, Ludwig E, Jaworowicz D, Huang H, Fiedler-Kelly J, Cortes J, Ganguly S, Khaled S, Kramer A, Levis M, Martinelli G, Perl A, Russell N, Abutarif M, Choi Y, Yin O. Concentration-QTc analysis of quizartinib in patients with relapsed/refractory acute myeloid leukemia. Cancer Chemother Pharmacol. 2021 Apr;87(4):513-523. doi: 10.1007/s00280-020-04204-y. Epub 2021 Jan 8.
- Derived from this study: PubMed 31175001Cortes JE, Khaled S, Martinelli G, Perl AE, Ganguly S, Russell N, Kramer A, Dombret H, Hogge D, Jonas BA, Leung AY, Mehta P, Montesinos P, Radsak M, Sica S, Arunachalam M, Holmes M, Kobayashi K, Namuyinga R, Ge N, Yver A, Zhang Y, Levis MJ. Quizartinib versus salvage chemotherapy in relapsed or refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): a multicentre, randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2019 Jul;20(7):984-997. doi: 10.1016/S1470-2045(19)30150-0. Epub 2019 Jun 4.
- Derived from this study: PubMed 29859851Cortes 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.
- Individual participant dataSharing planned: 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/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jorge E. Cortes, MD principal investigator
M.D. Anderson Cancer Center
Global Clinical Leader study director
Daiichi Sankyo
131 sites in 19 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Quizartinib and Salvage Chemotherapy in people with AML, run by Daiichi Sankyo at 131 sites in 19 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 12 inclusion and 21 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 24 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 131 sites in United States, Germany, Italy, France, Spain and 14 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 27 Jan 2020). 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?
Overall Survival in Participants That Received Quizartinib Versus Salvage Chemotherapy (time frame: At approximately 3 years 9 months). 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 NCT02039726, which also lists 3 linked publications.
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 24 Feb 2021.