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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02039726




Registration number
NCT02039726
Ethics application status
Date submitted
15/01/2014
Date registered
20/01/2014
Date last updated
24/02/2021

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
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United States of America
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Connecticut
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United States of America
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Georgia
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United States of America
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Illinois
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United States of America
State/province [5] 0 0
Indiana
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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
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Massachusetts
Country [10] 0 0
United States of America
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Michigan
Country [11] 0 0
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State/province [11] 0 0
Minnesota
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
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United States of America
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Nebraska
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United States of America
State/province [14] 0 0
New Jersey
Country [15] 0 0
United States of America
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New York
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North Carolina
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Ohio
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Oregon
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Pennsylvania
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United States of America
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South Dakota
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Tennessee
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United States of America
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Texas
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United States of America
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Washington
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Belgium
State/province [24] 0 0
BE
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Canada
State/province [25] 0 0
Alberta
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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
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Brno
Country [30] 0 0
Czechia
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Hradec Králové
Country [31] 0 0
Czechia
State/province [31] 0 0
Olomouc
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France
State/province [32] 0 0
Caen
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France
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Grenoble
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France
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Le Chesnay
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France
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Marseille
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France
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Nantes
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France
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Paris
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France
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Pessac
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France
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Rouen
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France
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Toulouse
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Germany
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Berlin
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Germany
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Braunschweig
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Germany
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Dresden
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Germany
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Frankfurt
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Germany
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Halle
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Germany
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Hanover
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Germany
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Heidelberg
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Germany
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Jena
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Germany
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Leipzig
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Germany
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Mainz
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Germany
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Marburg
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Germany
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Munchen
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Germany
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Münster
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Hong Kong
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Hong Kong
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Hungary
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Csongrad
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Hungary
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Hajdu Bihar
Country [57] 0 0
Hungary
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Pest
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Italy
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Bari
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Italy
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Bologna
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Italy
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Cagliari
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Italy
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Ferrara
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Italy
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Firenze
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Genova
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Italy
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Milan
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Italy
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Napoli
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Orbassano
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Rome
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Siena
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Varese
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Korea, Republic of
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Gyeonggi-do
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Korea, Republic of
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Daegu
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Korea, Republic of
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Seoul
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Netherlands
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Amsterdam
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Netherlands
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Groningen
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Netherlands
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Rotterdam
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Poland
State/province [76] 0 0
Bialystok
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Poland
State/province [77] 0 0
Katowice
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Poland
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Lublin
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Serbia
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Belgrade
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Serbia
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Novi Sad
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Singapore
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Singapore
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Spain
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De Mallorca
Country [83] 0 0
Spain
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SP
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Spain
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Barcelona
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Spain
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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
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02039726
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