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

Phase 3

Completed

• Conditions: AML
• Interventions: Drug: Salvage Chemotherapy; Drug: Quizartinib

• Registration Number: NCT02039726
• Lead Sponsor: Daiichi Sankyo

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-01-15
• Study First Submitted QC: 2014-01-16
• Study First Posted: 2014-01-20
• Study Start: 2014-05
• Primary Completion: 2018-02-22
• Results First Submitted: 2019-09-25
• Results First Submitted QC: 2020-01-14
• Results First Posted: 2020-01-27
• Study Completion: 2020-09-08
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-02
• Last Update Posted: 2021-02-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 367

Inclusion Criteria

1. 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.
2. Age ≥ 18 years or the minimum legal adult age (whichever is greater) at the time of Informed consent.
3. 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.
4. 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.
5. 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.
6. Eligibility for pre-selected salvage chemotherapy, according to the Investigator's assessment.
7. Eastern Cooperative Oncology Group (ECOG) performance score 0-2.
8. 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.
9. Serum creatinine ≤1.5×upper limit of normal (ULN), or glomerular filtration rate >25 mL/min, as calculated with the Cockcroft-Gault formula.
10. 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.
11. Total serum bilirubin ≤1.5×ULN.
12. Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤2.5×ULN.

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Exclusion Criteria

1. Acute Promyelocytic Leukemia (AML subtype M3).
2. AML secondary to prior chemotherapy for other neoplasms, except AML secondary to prior Myelodysplastic Syndrome (MDS).
3. History of another malignancy, unless the candidate has been disease-free for at least 5 years.
4. Persistent, clinically significant > Grade 1 non-hematologic toxicity from prior AML therapy.
5. 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.
6. History of or current, central nervous system involvement with AML.
7. Clinically significant coagulation abnormality, such as disseminated intravascular coagulation.
8. Prior treatment with quizartinib or participated in a prior quizartinib study.
9. Prior treatment with a FLT3 targeted therapy including sorafenib or investigational FLT3 inhibitors (not including the multi-kinase inhibitor, midostaurin).
10. Major surgery within 4 weeks prior to screening.
11. Radiation therapy within 4 weeks prior to screening.
12. Uncontrolled or significant cardiovascular disease
13. Active infection not well controlled by antibacterial or antiviral therapy.
14. Known infection with human immunodeficiency virus, or active hepatitis B or C, or other active clinically relevant liver disease.
15. Unwillingness to receive infusion of blood products according to the protocol.
16. 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.
17. 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.
18. Pregnancy.
19. 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.
20. 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.
21. 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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Salvage chemotherapy	Salvage Chemotherapy	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.
Quizartinib	Quizartinib	Participants who were randomized to receive 20 or 30 mg quizartinib tablets administered orally once daily.

Primary Outcome Measures

Name	Time	Method
Overall Survival in Participants That Received Quizartinib Versus Salvage Chemotherapy	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.

Secondary Outcome Measures

Name	Time	Method
Event-free Survival in Participants That Received Quizartinib Versus Salvage Chemotherapy	At approximately 3 years 9 months	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.

Trial Locations

Locations (131)

University of Southern California, Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

Emory Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

University of Pennsylvania Health System; 🇺🇸 Philadelphia, Pennsylvania, United States

CHU de Caen; 🇫🇷 Caen, France

University of Illinois at Chicago; 🇺🇸 Chicago, Illinois, United States

University of Chicago; 🇺🇸 Chicago, Illinois, United States

Centre Henri-Becquerel; 🇫🇷 Rouen, France

Hopital Saint-Antoine; 🇫🇷 Paris, France

UCLA Medical Center; 🇺🇸 Los Angeles, California, United States

Fakultni nemocnice Brno; 🇨🇿 Brno, Czechia

Klinička Bolinca Merkur; 🇭🇷 Zagreb, Croatia

Columbia University Medical Center; 🇺🇸 New York, New York, United States

UNC Linebreger Comprehensive Cancer Center; 🇺🇸 Chapel Hill, North Carolina, United States

University of Kansas Medical Center Research Institute Inc; 🇺🇸 Westwood, Kansas, United States

University of Alberta Hospital; 🇨🇦 Edmonton, Alberta, Canada

LSU Health Sciences Center Feist Weiller Cancer Center; 🇺🇸 Shreveport, Louisiana, United States

NY Medical College; 🇺🇸 Valhalla, New York, United States

Centre Hospitalier Universitaire Nantes; 🇫🇷 Nantes, France

ZNA Stuivenberg; 🇧🇪 Antwerpen, BE, Belgium

Alfred Hospital; 🇦🇺 Melbourne, Victoria, Australia

Hopital de la Conception; 🇫🇷 Marseille, France

Stanford University Medical Center Stanford Comprehensive Cancer Center; 🇺🇸 Stanford, California, United States

UCL St Luc; 🇧🇪 Brussels, BE, Belgium

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States

The Princess Alexandra Hospital; 🇦🇺 Brisbane, Queensland, Australia

Penn State Milton S Hershey Medical Center; 🇺🇸 Hershey, Pennsylvania, United States

The Queen Elizabeth Hospital; 🇦🇺 Woodville, South Australia, Australia

Azienda Ospedaliero Universitaria Senese, Policlinico S. Maria alle Scotte; 🇮🇹 Siena, Italy

Princess Margaret Cancer Centre Princess Margaret Hospital; 🇨🇦 Toronto, Ontario, Canada

Vancouver General Hospital; 🇨🇦 Vancouver, British Columbia, Canada

Ospedale di Circolo-a Fondazione Macchi; 🇮🇹 Varese, Italy

Seoul National University Bundang Hospital; 🇰🇷 Seongnam-si, Gyeonggi-do, Korea, Republic of

Centre Hospitalier de Versailles; 🇫🇷 Le Chesnay, France

Medizinische Hochschule Hannover; 🇩🇪 Hanover, Germany

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Kyungpook National University Hospital; 🇰🇷 Daegu, Korea, Republic of

Kliničko Bolnički Centar Zagreb; 🇭🇷 Zagreb, Croatia

Uniwersytecki Szpital Kliniczny w Biatymstoku, Klinika Hematologii z Pododzialem Chorob Naczyn; 🇵🇱 Bialystok, Poland

Policlinico Universitario Agostino Gemelli; 🇮🇹 Rome, Italy

Fakultni nemocnice Hradec Kralove; 🇨🇿 Hradec Králové, Czechia

VU Medisch Centrum; 🇳🇱 Amsterdam, Netherlands

Centre Hospitalier Universitaire Grenoble Hopital Michalon; 🇫🇷 Grenoble, France

Universitätsklinikum Halle; 🇩🇪 Halle, Germany

Charité Universitätsmedizin Berlin; 🇩🇪 Berlin, Germany

Klinikum Braunschweig; 🇩🇪 Braunschweig, Germany

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

The Catholic University of Korea Seoul St. Mary's Hospital; 🇰🇷 Seoul, Korea, Republic of

Hospital Universitario Virgen del Rocio; 🇪🇸 Sevilla, Spain

The University of Hong Kong, Queen Mary Hospital; 🇭🇰 Hong Kong, Hong Kong

Hopital Haut Leveque Centre Francois Magendie; 🇫🇷 Pessac, France

Hospital General Universitario Gregorio Marañon; 🇪🇸 Madrid, Spain

AOU Careggi; 🇮🇹 Firenze, Italy

Ospedale San Raffaele; 🇮🇹 Milan, Italy

University Mainz; 🇩🇪 Mainz, Germany

Arcispedale S Anna; 🇮🇹 Ferrara, Italy

University Hospital of Wales; 🇬🇧 Cardiff, South Glamorgan, United Kingdom

Universitatsklinikum Dresden; 🇩🇪 Dresden, Germany

Hospital La Fe; 🇪🇸 Valencia, SP, Spain

Hospital Clinic I Provincial de Barcelona; 🇪🇸 Barcelona, Spain

National University of Singapore; 🇸🇬 Singapore, Singapore

Complejo Hospitalario de Navarra; 🇪🇸 Pamplona, Spain

Samodzielny Publiczny Szpital Kliniczny im. Andrzeja Mieleckiego Slaskiego Uniwersytetu Medycznego w Katowicach Oddzial Hematologii i Transplantacji Szpiku; 🇵🇱 Katowice, Poland

Bristol Haematology and Oncology Centre; 🇬🇧 Bristol, England, United Kingdom

Aberdeen Royal Infirmary; 🇬🇧 Aberdeen, Scotland, United Kingdom

University of Maryland; 🇺🇸 Baltimore, Maryland, United States

Leuven UZ Gasthuisberg; 🇧🇪 Leuven, BE, Belgium

Barbara Ann Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Franciscan Alliance; 🇺🇸 Indianapolis, Indiana, United States

Duke Cancer Institute at Duke University Health System; 🇺🇸 Durham, North Carolina, United States

Vanderbilt-Ingram Cancer Center; 🇺🇸 Nashville, Tennessee, United States

MD Anderson Center, The University of Texas; 🇺🇸 Houston, Texas, United States

Swedish Cancer Institute; 🇺🇸 Seattle, Washington, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

City of Hope National Medical Center; 🇺🇸 Duarte, California, United States

University of Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

University of Rochester; 🇺🇸 Rochester, New York, United States

China Medical University Hospital; 🇨🇳 Taichung, Taiwan

National Cheng Kung University Hospital; 🇨🇳 Tainan, Taiwan

King's College Hospital; 🇬🇧 London, England, United Kingdom

Singapore General Hospital; 🇸🇬 Singapore, Singapore

Nottingham City Hospital NHS Trust; 🇬🇧 Nottingham, England, United Kingdom

Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan

Royal Marsden Hospital Sutton; 🇬🇧 Sutton, England, United Kingdom

Hospital Universitari Germans Trias i Pujol; 🇪🇸 Barcelona, Spain

Geisinger Medical Center; 🇺🇸 Danville, Pennsylvania, United States

The Canbera Hospital; 🇦🇺 Garran, New South Wales, Australia

Hôpital Saint Louis; 🇫🇷 Paris, France

Centre Hospitalier Universitaire Purpan; 🇫🇷 Toulouse, France

Charité Campus Virchow Klinikum; 🇩🇪 Berlin, Germany

Klinikum der Johann Wolfgang-Goethe-Universität; 🇩🇪 Frankfurt, Germany

Universitätsklinikum Giessen und Marburg GmbH; 🇩🇪 Marburg, Germany

Debreceni Egyetem Klinikai Kozpont, Belgyogyaszati Intezet; 🇭🇺 Debrecen, Hajdu Bihar, Hungary

LMU München Klinikum Großhadern; 🇩🇪 Munchen, Germany

Szegedi Tudomanyegyetem Altalanos Orvostudomanyi Kar Szent Gyorgyi Albert Klinikai Kozpont; 🇭🇺 Szeged, Csongrad, Hungary

AOU Policlinico Consorziale di Bari; 🇮🇹 Bari, Italy

Università di Bologna; 🇮🇹 Bologna, Italy

Semmelweis Egyetem Altalanos Orvostudomanyi Kar I. Belgyogyaszati Klinika; 🇭🇺 Budapest, Pest, Hungary

Unità Operativa di Ematologia e Unità Operativa CTMO; 🇮🇹 Cagliari, Italy

IRCCS Azienda Ospedaliera Universitaria San Martino; 🇮🇹 Genova, Italy

Opsedale San Martino di Genova; 🇮🇹 Genova, Italy

Azienda Ospedaliera Universitaria Federico II; 🇮🇹 Napoli, Italy

Azienda Ospedaliero Universitaria San Luigi Gonzaga; 🇮🇹 Orbassano, Italy

L'UOC di Ematologia del Policlinico Tor Vergata; 🇮🇹 Rome, Italy

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Erasmus Medical Center; 🇳🇱 Rotterdam, Netherlands

Universitair Medisch Centrum Groningen; 🇳🇱 Groningen, Netherlands

Samodzielny Publiczny Szpital Kliniczny Nr 1, Klinika Hematoonkologii i Transplantacji Szpiku; 🇵🇱 Lublin, Poland

Klinicki Centar Srbije; 🇷🇸 Belgrade, Serbia

Hospital Son Espases; 🇪🇸 Palma, De Mallorca, Spain

Klinicki Centar Vojvodine; 🇷🇸 Novi Sad, Serbia

Hospital Clínico Universitario de Salamanca; 🇪🇸 Salamanca, Spain

Saint James University Hospital; 🇬🇧 Leeds, England, United Kingdom

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Uniklinik Heidelberg Medizinische Klinik und Poliklinik V; 🇩🇪 Heidelberg, Germany

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

Universitätsklinikum Jena; 🇩🇪 Jena, Germany

John Theurer Cancer Center at Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States

Fakultni nemocnice Olomouc; 🇨🇿 Olomouc, Czechia

Avera Cancer Institute; 🇺🇸 Sioux Falls, South Dakota, United States

Westmead Hospital; 🇦🇺 Westmead, New South Wales, Australia

Universitätsklinikum Leipzig; 🇩🇪 Leipzig, Germany

Medizinische Klinik A Hämatologie Hämostaseologie Internistische Onkologie und Pneumologie; 🇩🇪 Münster, Germany

UC Davis Cancer Center; 🇺🇸 Sacramento, California, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States

University of Michigan Health System; 🇺🇸 Ann Arbor, Michigan, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

University of Nebraska Medical Center; 🇺🇸 Omaha, Nebraska, United States

Wake Forest University Baptist Health; 🇺🇸 Winston-Salem, North Carolina, United States

Oregon Health and Science University Knight Cancer Institute; 🇺🇸 Portland, Oregon, United States

The Chinese University of Hong Kong, Prince of Wales Hospital; 🇭🇰 Hong Kong, Hong Kong