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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02039726




Registration number
NCT02039726
Ethics application status
Date submitted
15/01/2014
Date registered
20/01/2014

Titles & IDs
Public title
(QuANTUM-R): An Open-label Study of Quizartinib Monotherapy vs. Salvage Chemotherapy in Acute Myeloid Leukemia (AML) Subjects Who Are FLT3-ITD Positive
Scientific 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
Secondary ID [1] 0 0
EudraCT Number 2013-004890-28
Secondary ID [2] 0 0
AC220-007
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
AML 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Quizartinib
Treatment: Drugs - Salvage Chemotherapy

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

Active comparator: 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.


Treatment: Drugs: Quizartinib
20 or 30 mg quizartinib tablets administered orally once daily

Treatment: Drugs: Salvage Chemotherapy
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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival in Participants That Received Quizartinib Versus Salvage Chemotherapy
Timepoint [1] 0 0
At approximately 3 years 9 months
Secondary outcome [1] 0 0
Event-free Survival in Participants That Received Quizartinib Versus Salvage Chemotherapy
Timepoint [1] 0 0
At approximately 3 years 9 months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/09/2020
Sample size
Target
Accrual to date
Final
367
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
The Canbera Hospital - Garran
Recruitment hospital [2] 0 0
Westmead Hospital - Westmead
Recruitment hospital [3] 0 0
The Princess Alexandra Hospital - Brisbane
Recruitment hospital [4] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [5] 0 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [6] 0 0
Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
- Brisbane
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
5011 - Woodville
Recruitment postcode(s) [6] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Kansas
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Minnesota
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
Nebraska
Country [14] 0 0
United States of America
State/province [14] 0 0
New Jersey
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Ohio
Country [18] 0 0
United States of America
State/province [18] 0 0
Oregon
Country [19] 0 0
United States of America
State/province [19] 0 0
Pennsylvania
Country [20] 0 0
United States of America
State/province [20] 0 0
South Dakota
Country [21] 0 0
United States of America
State/province [21] 0 0
Tennessee
Country [22] 0 0
United States of America
State/province [22] 0 0
Texas
Country [23] 0 0
United States of America
State/province [23] 0 0
Washington
Country [24] 0 0
Belgium
State/province [24] 0 0
BE
Country [25] 0 0
Canada
State/province [25] 0 0
Alberta
Country [26] 0 0
Canada
State/province [26] 0 0
British Columbia
Country [27] 0 0
Canada
State/province [27] 0 0
Ontario
Country [28] 0 0
Croatia
State/province [28] 0 0
Zagreb
Country [29] 0 0
Czechia
State/province [29] 0 0
Brno
Country [30] 0 0
Czechia
State/province [30] 0 0
Hradec Králové
Country [31] 0 0
Czechia
State/province [31] 0 0
Olomouc
Country [32] 0 0
France
State/province [32] 0 0
Caen
Country [33] 0 0
France
State/province [33] 0 0
Grenoble
Country [34] 0 0
France
State/province [34] 0 0
Le Chesnay
Country [35] 0 0
France
State/province [35] 0 0
Marseille
Country [36] 0 0
France
State/province [36] 0 0
Nantes
Country [37] 0 0
France
State/province [37] 0 0
Paris
Country [38] 0 0
France
State/province [38] 0 0
Pessac
Country [39] 0 0
France
State/province [39] 0 0
Rouen
Country [40] 0 0
France
State/province [40] 0 0
Toulouse
Country [41] 0 0
Germany
State/province [41] 0 0
Berlin
Country [42] 0 0
Germany
State/province [42] 0 0
Braunschweig
Country [43] 0 0
Germany
State/province [43] 0 0
Dresden
Country [44] 0 0
Germany
State/province [44] 0 0
Frankfurt
Country [45] 0 0
Germany
State/province [45] 0 0
Halle
Country [46] 0 0
Germany
State/province [46] 0 0
Hanover
Country [47] 0 0
Germany
State/province [47] 0 0
Heidelberg
Country [48] 0 0
Germany
State/province [48] 0 0
Jena
Country [49] 0 0
Germany
State/province [49] 0 0
Leipzig
Country [50] 0 0
Germany
State/province [50] 0 0
Mainz
Country [51] 0 0
Germany
State/province [51] 0 0
Marburg
Country [52] 0 0
Germany
State/province [52] 0 0
Munchen
Country [53] 0 0
Germany
State/province [53] 0 0
Münster
Country [54] 0 0
Hong Kong
State/province [54] 0 0
Hong Kong
Country [55] 0 0
Hungary
State/province [55] 0 0
Csongrad
Country [56] 0 0
Hungary
State/province [56] 0 0
Hajdu Bihar
Country [57] 0 0
Hungary
State/province [57] 0 0
Pest
Country [58] 0 0
Italy
State/province [58] 0 0
Bari
Country [59] 0 0
Italy
State/province [59] 0 0
Bologna
Country [60] 0 0
Italy
State/province [60] 0 0
Cagliari
Country [61] 0 0
Italy
State/province [61] 0 0
Ferrara
Country [62] 0 0
Italy
State/province [62] 0 0
Firenze
Country [63] 0 0
Italy
State/province [63] 0 0
Genova
Country [64] 0 0
Italy
State/province [64] 0 0
Milan
Country [65] 0 0
Italy
State/province [65] 0 0
Napoli
Country [66] 0 0
Italy
State/province [66] 0 0
Orbassano
Country [67] 0 0
Italy
State/province [67] 0 0
Rome
Country [68] 0 0
Italy
State/province [68] 0 0
Siena
Country [69] 0 0
Italy
State/province [69] 0 0
Varese
Country [70] 0 0
Korea, Republic of
State/province [70] 0 0
Gyeonggi-do
Country [71] 0 0
Korea, Republic of
State/province [71] 0 0
Daegu
Country [72] 0 0
Korea, Republic of
State/province [72] 0 0
Seoul
Country [73] 0 0
Netherlands
State/province [73] 0 0
Amsterdam
Country [74] 0 0
Netherlands
State/province [74] 0 0
Groningen
Country [75] 0 0
Netherlands
State/province [75] 0 0
Rotterdam
Country [76] 0 0
Poland
State/province [76] 0 0
Bialystok
Country [77] 0 0
Poland
State/province [77] 0 0
Katowice
Country [78] 0 0
Poland
State/province [78] 0 0
Lublin
Country [79] 0 0
Serbia
State/province [79] 0 0
Belgrade
Country [80] 0 0
Serbia
State/province [80] 0 0
Novi Sad
Country [81] 0 0
Singapore
State/province [81] 0 0
Singapore
Country [82] 0 0
Spain
State/province [82] 0 0
De Mallorca
Country [83] 0 0
Spain
State/province [83] 0 0
SP
Country [84] 0 0
Spain
State/province [84] 0 0
Barcelona
Country [85] 0 0
Spain
State/province [85] 0 0
Madrid
Country [86] 0 0
Spain
State/province [86] 0 0
Pamplona
Country [87] 0 0
Spain
State/province [87] 0 0
Salamanca
Country [88] 0 0
Spain
State/province [88] 0 0
Sevilla
Country [89] 0 0
Taiwan
State/province [89] 0 0
Taichung
Country [90] 0 0
Taiwan
State/province [90] 0 0
Tainan
Country [91] 0 0
Taiwan
State/province [91] 0 0
Taipei
Country [92] 0 0
United Kingdom
State/province [92] 0 0
England
Country [93] 0 0
United Kingdom
State/province [93] 0 0
Scotland
Country [94] 0 0
United Kingdom
State/province [94] 0 0
South Glamorgan

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Daiichi Sankyo
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jorge E. Cortes, MD
Address 0 0
M.D. Anderson Cancer Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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/

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/ourmember/daiichi-sankyo/


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02039726