(QuANTUM-R): An Open-label Study of Quizartinib Monotherapy vs. Salvage Chemotherapy in Acute Myeloid Leukemia (AML) Subjects Who Are FLT3-ITD Positive

NCT02039726 | Completed Phase 3 Results DMC

• 2 other identifiers: AC220-007EudraCT Number 2013-004890-28
• Study Type: interventional
• Target: 367
• Locations: 19 countries
• Sites: 131

Brief 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 AML therapy.

Conditions

AML

Keywords

Acute Myeloid Leukemia; AML; FMS-like tyrosine kinase 3; FLT3-ITD; Quizartinib; Leukemia; Tablets

Outcome Measures

Primary Outcomes (1)

• 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.

  At approximately 3 years 9 months

Secondary Outcomes (1)

• Event-free Survival in Participants That Received Quizartinib Versus Salvage Chemotherapy

  At approximately 3 years 9 months

Study Arms (2)

Quizartinib

EXPERIMENTAL

Participants who were randomized to receive 20 or 30 mg quizartinib tablets administered orally once daily.

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.

Drug: Salvage Chemotherapy

Interventions

Quizartinib DRUG

20 or 30 mg quizartinib tablets administered orally once daily

Also known as: AC220

Quizartinib

Salvage Chemotherapy DRUG

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

Also known as: Standard of Care

Salvage chemotherapy

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (131)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of Southern California, Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

UC Davis Cancer Center

Sacramento, California, 95817, United States

Location

Stanford University Medical Center Stanford Comprehensive Cancer Center

Stanford, California, 94305, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Emory Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60607, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Franciscan Alliance

Indianapolis, Indiana, 46237, United States

Location

University of Kansas Medical Center Research Institute Inc

Westwood, Kansas, 66205, United States

Location

LSU Health Sciences Center Feist Weiller Cancer Center

Shreveport, Louisiana, 71103, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

NY Medical College

Valhalla, New York, 10595, United States

Location

UNC Linebreger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Duke Cancer Institute at Duke University Health System

Durham, North Carolina, 27710, United States

Location

Wake Forest University Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Oregon Health and Science University Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

University of Pennsylvania Health System

Philadelphia, Pennsylvania, 19104, United States

Location

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MD Anderson Center, The University of Texas

Houston, Texas, 77030, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

The Canbera Hospital

Garran, New South Wales, 2605, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

The Princess Alexandra Hospital

Brisbane, Queensland, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

The Queen Elizabeth Hospital

Woodville, South Australia, 5011, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

ZNA Stuivenberg

Antwerp, BE, 2060, Belgium

Location

UCL St Luc

Brussels, BE, 1200, Belgium

Location

Leuven UZ Gasthuisberg

Leuven, BE, 3000, Belgium

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Princess Margaret Cancer Centre Princess Margaret Hospital

Toronto, Ontario, M5G2M9, Canada

Location

Klinička Bolinca Merkur

Zagreb, 10000, Croatia

Location

Kliničko Bolnički Centar Zagreb

Zagreb, 10000, Croatia

Location

Fakultni nemocnice Brno

Brno, 62500, Czechia

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 50005, Czechia

Location

Fakultni nemocnice Olomouc

Olomouc, 77900, Czechia

Location

CHU de Caen

Caen, 14000, France

Location

Centre Hospitalier Universitaire Grenoble Hopital Michalon

Grenoble, 38043, France

Location

Centre Hospitalier de Versailles

Le Chesnay, 78157, France

Location

Hopital de la Conception

Marseille, 13385, France

Location

Centre Hospitalier Universitaire Nantes

Nantes, 44035, France

Location

Hôpital Saint Louis

Paris, 75010, France

Location

Hopital Saint-Antoine

Paris, 75571, France

Location

Hopital Haut Leveque Centre Francois Magendie

Pessac, 33604, France

Location

Centre Henri-Becquerel

Rouen, 76038, France

Location

Centre Hospitalier Universitaire Purpan

Toulouse, 31059, France

Location

Charité Universitätsmedizin Berlin

Berlin, 12200, Germany

Location

Charité Campus Virchow Klinikum

Berlin, 13353, Germany

Location

Klinikum Braunschweig

Braunschweig, 38114, Germany

Location

Universitatsklinikum Dresden

Dresden, 01307, Germany

Location

Klinikum der Johann Wolfgang-Goethe-Universität

Frankfurt, 60590, Germany

Location

Universitätsklinikum Halle

Halle, 06120, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Uniklinik Heidelberg Medizinische Klinik und Poliklinik V

Heidelberg, 69120, Germany

Location

Universitätsklinikum Jena

Jena, 07743, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

University Mainz

Mainz, 55131, Germany

Location

Universitätsklinikum Giessen und Marburg GmbH

Marburg, 35043, Germany

Location

LMU München Klinikum Großhadern

München, 81377, Germany

Location

Medizinische Klinik A Hämatologie Hämostaseologie Internistische Onkologie und Pneumologie

Münster, 48149, Germany

Location

The Chinese University of Hong Kong, Prince of Wales Hospital

Hong Kong, Hong Kong

Location

The University of Hong Kong, Queen Mary Hospital

Hong Kong, Hong Kong

Location

Szegedi Tudomanyegyetem Altalanos Orvostudomanyi Kar Szent Gyorgyi Albert Klinikai Kozpont

Szeged, Csongrád megye, 6725, Hungary

Location

Debreceni Egyetem Klinikai Kozpont, Belgyogyaszati Intezet

Debrecen, Hajdú-Bihar, 4032, Hungary

Location

Semmelweis Egyetem Altalanos Orvostudomanyi Kar I. Belgyogyaszati Klinika

Budapest, Pest County, 1083, Hungary

Location

AOU Policlinico Consorziale di Bari

Bari, 70124, Italy

Location

Università di Bologna

Bologna, 40138, Italy

Location

Unità Operativa di Ematologia e Unità Operativa CTMO

Cagliari, Italy

Location

Arcispedale S Anna

Ferrara, 44124, Italy

Location

AOU Careggi

Florence, 50134, Italy

Location

IRCCS Azienda Ospedaliera Universitaria San Martino

Genova, 16132, Italy

Location

Opsedale San Martino di Genova

Genova, 16132, Italy

Location

Ospedale San Raffaele

Milan, 20132, Italy

Location

Azienda Ospedaliera Universitaria Federico II

Napoli, 80131, Italy

Location

Azienda Ospedaliero Universitaria San Luigi Gonzaga

Orbassano, 10043, Italy

Location

L'UOC di Ematologia del Policlinico Tor Vergata

Rome, 00133, Italy

Location

Policlinico Universitario Agostino Gemelli

Rome, 00168, Italy

Location

Azienda Ospedaliero Universitaria Senese, Policlinico S. Maria alle Scotte

Siena, 53100, Italy

Location

Ospedale di Circolo-a Fondazione Macchi

Varese, 21100, Italy

Location

VU Medisch Centrum

Amsterdam, 1081 HV, Netherlands

Location

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ, Netherlands

Location

Erasmus Medical Center

Rotterdam, 3015 CE, Netherlands

Location

Uniwersytecki Szpital Kliniczny w Biatymstoku, Klinika Hematologii z Pododzialem Chorob Naczyn

Bialystok, 15276, Poland

Location

Samodzielny Publiczny Szpital Kliniczny im. Andrzeja Mieleckiego Slaskiego Uniwersytetu Medycznego w Katowicach Oddzial Hematologii i Transplantacji Szpiku

Katowice, 40032, Poland

Location

Samodzielny Publiczny Szpital Kliniczny Nr 1, Klinika Hematoonkologii i Transplantacji Szpiku

Lublin, 20081, Poland

Location

Klinicki Centar Srbije

Belgrade, 11000, Serbia

Location

Klinicki Centar Vojvodine

Novi Sad, 21000, Serbia

Location

National University of Singapore

Singapore, 119228, Singapore

Location

Singapore General Hospital

Singapore, 169608, Singapore

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 463-707, South Korea

Location

Kyungpook National University Hospital

Daegu, 700-721, South Korea

Location

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

Samsung Medical Center

Seoul, 135-710, South Korea

Location

The Catholic University of Korea Seoul St. Mary's Hospital

Seoul, 137-701, South Korea

Location

Asan Medical Center

Seoul, 138-736, South Korea

Location

Hospital Son Espases

Palma, De Mallorca, 07120, Spain

Location

Hospital La Fe

Valencia, SP, 46026, Spain

Location

Hospital Clinic I Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitari Germans Trias i Pujol

Barcelona, 08916, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, 31008, Spain

Location

Hospital Clínico Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

China Medical University Hospital

Taichung, 404, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

Bristol Haematology and Oncology Centre

Bristol, England, BS2 8ED, United Kingdom

Location

Saint James University Hospital

Leeds, England, LS9 7TF, United Kingdom

Location

King's College Hospital

London, England, SE5 9RS, United Kingdom

Location

Nottingham City Hospital NHS Trust

Nottingham, England, NG51PB, United Kingdom

Location

Royal Marsden Hospital Sutton

Sutton, England, SM2 5PT, United Kingdom

Location

Aberdeen Royal Infirmary

Aberdeen, Scotland, AB25 2ZN, United Kingdom

Location

University Hospital of Wales

Cardiff, South Glamorgan, CF14 4XW, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 33415416 DERIVED

• Cortes 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.

  PMID: 31175001 DERIVED

• 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

Interventions

quizartinib; Standard of Care

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

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

CTRinfo@dsi.com

1-908-992-6400

Study Officials

• Jorge E. Cortes, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2014
• First Posted: January 20, 2014
• Study Start: May 1, 2014
• Primary Completion: February 22, 2018
• Study Completion: September 8, 2020
• Last Updated: February 24, 2021
• Results First Posted: January 27, 2020

Record last verified: 2021-02

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

PL (3); HK (2); US (36); KR (6); SE (2); IT (14); HU (3); FR (10); DE (14); NL (3); CR (2); TW (4); GB (7); CA (3); SG (2); BE (3); CZ (3); ES (8); AU (6)