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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02752035




Registration number
NCT02752035
Ethics application status
Date submitted
22/04/2016
Date registered
26/04/2016
Date last updated
9/06/2021

Titles & IDs
Public title
A Study of ASP2215 (Gilteritinib) by Itself, ASP2215 Combined With Azacitidine or Azacitidine by Itself to Treat Adult Patients Who Have Recently Been Diagnosed With Acute Myeloid Leukemia With a FLT3 Gene Mutation and Who Cannot Receive Standard Chemotherapy
Scientific title
A Phase 3 Multicenter, Open-label, Randomized Study of ASP2215 (Gilteritinib), Combination of ASP2215 Plus Azacitidine and Azacitidine Alone in the Treatment of Newly Diagnosed Acute Myeloid Leukemia With FLT3 Mutation in Patients Not Eligible for Intensive Induction Chemotherapy
Secondary ID [1] 0 0
2015-001790-41
Secondary ID [2] 0 0
2215-CL-0201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia (AML) 0 0
Acute Myeloid Leukemia With FMS-like Tyrosine Kinase (FLT3) Mutation 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(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - gilteritinib
Treatment: Drugs - azacitidine

Experimental: Dose escalation of ASP2215 given with azacitidine - Subjects will be treated with ASP2215 daily (days 1-28) and azacitidine daily for 7 days (days 1-7).

Experimental: Arm A: ASP2215 - Subjects will be treated daily each 28-day cycle.

Experimental: Arm AC: ASP2215 + azacitidine - Subjects will be treated with ASP2215 daily and azacitidine daily for 7 days (days 1-7) each 28-day cycle.

Active Comparator: Arm C: azacitidine - Subjects will be treated with azacitidine for 7 days (days 1-7) each 28-day cycle.


Treatment: Drugs: gilteritinib
Tablet, oral

Treatment: Drugs: azacitidine
Subcutaneous injection or intravenous infusion

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

Outcomes
Primary outcome [1] 0 0
Overall survival (OS) - OS is defined as the time from the date of randomization until the date of death from any cause.
Timepoint [1] 0 0
Up to 77 months
Secondary outcome [1] 0 0
Event free survival (EFS) - EFS is defined as the time from the date of randomization until the date of documented relapse from complete remission (CR), treatment failure or death from any cause, whichever occurs first.
Timepoint [1] 0 0
Up to 77 months
Secondary outcome [2] 0 0
Best response - Best response is defined as the best measured response (in the order of CR, CRp, Cri or treatment failure defined by lack of composite complete remission (CRc)) from all post-baseline visits.
Timepoint [2] 0 0
Up to 48 months
Secondary outcome [3] 0 0
Complete remission (CR) rate - Complete remission rate is defined as the number of patients with all complete CRs.
Timepoint [3] 0 0
Up to 48 months
Secondary outcome [4] 0 0
Composite complete remission (CRc) rate - CRc rate is defined as the number of patients with all complete and incomplete CRs (i.e., CR + Complete remission with incomplete platelet recovery (CRp) + Complete remission with incomplete hematologic recovery (Cri)).
Timepoint [4] 0 0
Up to 48 months
Secondary outcome [5] 0 0
Complete remission with partial hematologic recovery (CRh) rate - CRh rate is defined as the number of patients who achieve CRh at any of the post-baseline visits and do not have best response of CR divided by the number of patients in the analysis population.
Timepoint [5] 0 0
Up to 48 months
Secondary outcome [6] 0 0
Complete remission and complete remission with partial hematological recovery (CR/CRh) rate - CR/CRh rate is defined as the number of patients who achieve either CR or CRh at any of the post-baseline visits divided by the number of patients in the analysis population.
Timepoint [6] 0 0
Up to 48 months
Secondary outcome [7] 0 0
Transfusion conversion rate - Transfusion conversion rate is defined as the number of patients who were transfusion dependent at the baseline period but become transfusion independent at the post-baseline period divided by the total number of patients who were transfusion dependent at baseline period.
Timepoint [7] 0 0
Up to 49 months
Secondary outcome [8] 0 0
Transfusion maintenance rate - Transfusion maintenance rate is defined as the number of patients who were transfusion independent at the baseline period and still maintain transfusion independence at the post-baseline period divided by the number of patients who were transfusion independent at baseline period.
Timepoint [8] 0 0
Up to 49 months
Secondary outcome [9] 0 0
Leukemia free survival (LFS) - LFS is defined as the time from the date of first composite complete remission (CRc) until the date of documented relapse or death for subjects who achieve CRc.
Timepoint [9] 0 0
Up to 77 months
Secondary outcome [10] 0 0
Duration of remission - Duration of remission includes duration of CRc, CR, Cri, CRp and response (CRc + partial response [PR]). Duration of CRc is defined as the time from the date of first CRc until the date of documented relapse for subjects who achieve CRc. Duration of remission is similarly defined for CR, Cri and CRp.
Timepoint [10] 0 0
Up to 48 months
Secondary outcome [11] 0 0
Participant reported fatigue from Brief Fatigue Inventory (BFI) - The BFI was developed to assess the severity of fatigue and the impact of fatigue on daily functioning in subjects with fatigue due to cancer and cancer treatment The BFI inventory has 9 items and a 24-hour recall. A global fatigue score is computed by averaging the 9 items.
Timepoint [11] 0 0
Up to 48 months
Secondary outcome [12] 0 0
Safety assessed by adverse events (AEs)
Timepoint [12] 0 0
Up to 49 months
Secondary outcome [13] 0 0
Number of participants with abnormal laboratory values and/or adverse events related to treatment
Timepoint [13] 0 0
Up to 48 months
Secondary outcome [14] 0 0
Number of participants with abnormal vital signs and/or adverse events related to treatment
Timepoint [14] 0 0
Up to 48 months
Secondary outcome [15] 0 0
Number of participants with Physical Exam abnormalities and/or adverse events - Number of participants with potentially clinically significant physical exam values.
Timepoint [15] 0 0
Up to 48 months
Secondary outcome [16] 0 0
Safety assessed by electrocardiograms (ECGs) - The 12-lead ECGs will be recorded in triplicate (3 separate ECGs) and transmitted electronically for central reading. The mean of the triplicate ECG from central read will be used for all final treatment decisions and adverse event reporting.
Timepoint [16] 0 0
Up to 48 months
Secondary outcome [17] 0 0
Eastern Cooperative Oncology Group (ECOG) performance status score - ECOG performance status measured on 6 point scale to assess participant's performance status. 0=Fully active, able to carry on all pre-disease activities without restriction; 1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; 2= Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3=Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4=Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair; 5=Dead. 0=Best status; 5=Worst status.
Timepoint [17] 0 0
Up to 48 months

Eligibility
Key inclusion criteria
- Subject is considered an adult according to local regulation at the time of obtaining
informed consent.

- Subject has a diagnosis of previously-untreated AML according to World Health
Organization (WHO) classification [Swerdlow et al, 2008] as determined by pathology
review at the treating institution.

- Subject is positive for FLT3 mutation (internal tandem duplication [ITD] or tyrosine
kinase domain [TKD] [D835/I836] mutation) (or for Korea only: ITD alone or ITD with
concurrent TKD activating mutation) in bone marrow or whole blood as determined by
central laboratory. Note: Only requirement of FLT3 mutation assessment by central
laboratory is only applicable to the randomization portion of the study.

- Subject is ineligible for intensive induction chemotherapy by meeting at least 1 of
the following criteria:

- Subject is = 65 years of age and ineligible for intensive induction chemotherapy.

- Subject is = 18 to 64 years of age and has any of the following comorbidities:
[Ex-US Only]: Congestive heart failure (New York Heart Association {NYHA} class =
3) or ejection fraction (Ef) = 50%; [US Only]: Severe cardiac disorder e.g.
congestive heart failure (New York Heart Association [NYHA] class = 3) requiring
treatment, ejection fraction = 50%, or chronic stable angina; [Ex-US Only]:
Creatinine > 2 mg/dL (177 µmol/L), dialysis or prior renal transplant; [US Only]:
Creatinine clearance < 45 mL/min; ECOG performance status = 2;

- [Ex-US Only]: Known pulmonary disease with decreased diffusion capacity of lung
for carbon monoxide (DLCO) and/or requiring oxygen = 2 liters per minute; [US
Only] Severe pulmonary disorder (e.g., diffusion capacity of lung for carbon
monoxide [DLCO] = 65% or forced expiratory volume in the first second [FEV1] =
65%); Prior or current malignancy that does not require concurrent treatment;
Subject has received a cumulative anthracycline dose above 400 mg/m2 of
doxorubicin (or cumulative maximum dose of another anthracycline). Any other
comorbidity incompatible with intensive chemotherapy must be reviewed and
approved by the Medical Monitor during screening and before randomization.

- Subject must meet the following criteria as indicated on the clinical laboratory
tests:

- Serum AST and ALT = 3.0 x Institutional upper limit of normal (ULN)

- Serum total bilirubin = 1.5 x Institutional ULN

- Serum potassium = Institutional lower limit of normal (LLN)

- Serum magnesium = Institutional LLN Repletion of potassium and magnesium levels
during the screening period is allowed.

- Subject is suitable for oral administration of study drug.

- Female subject is eligible to participate if female subject is not pregnant and at
least one of the following conditions applies:

- Not a woman of childbearing potential (WOCBP); OR

- WOCBP agrees to follow the contraceptive guidance starting at screening and
continue throughout the study period, and for at least 180 days after the final
study drug administration.

- Female subject must agree not to breastfeed starting at screening and throughout the
study period, and for 60 days after the final study drug administration.

- Female subject must not donate ova starting at screening and throughout the study
period, and for 180 days after the final study drug administration.

- Male subject with female partners of childbearing potential must agree to use
contraception as detailed in Contraception Requirements, starting at screening and
continue throughout the study period, and for 120 days after the final study drug
administration.

- Male subject must not donate sperm starting at screening and throughout the study
period and for 120 days after the final study drug administration.

- Subject agrees not to participate in another interventional study while on treatment.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Subject was diagnosed as acute promyelocytic leukemia (APL).

- Subject has BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).

- Subject has received previous therapy for AML, with the exception of the following:

- Emergency leukapheresis

- Hydroxyurea

- Preemptive treatment with retinoic acid prior to exclusion of APL = 7 days

- Growth factor or cytokine support

- Steroids

- Subject has clinically active central nervous system leukemia.

- Subject has been diagnosed with another malignancy that requires concurrent treatment
(with the exception of hormone therapy limited to those therapies that prevent
recurrence and/or spread of cancer) or hepatic malignancy regardless of need for
treatment.

- Subject requires treatment with concomitant drugs that are strong inducers of
cytochrome P450 CYP3A/P-glycoprotein (P-gp).

- Subject requires treatment with concomitant drugs that are strong inhibitors or
inducers of P-gp with the exception of drugs that are considered absolutely essential
for the care of the subject.

- Subject requires treatment with concomitant drugs that target serotonin
5-hydroxytryptamine receptor 2B (5HT2BR) or sigma nonspecific receptor with the
exception of drugs that are considered absolutely essential for the care of the
subject.

- Subject has congestive heart failure classified as New York Heart Association Class
IV.

- Subject with mean Fridericia-corrected QT interval (QTcF) > 480 ms at screening based
on central reading.

- Subject with a history of Long QT Syndrome at screening.

- [Ex-US Only]: Subject has known pulmonary function tests with diffusion capacity of
lung for carbon monoxide (DLCO) = 50%, forced expiratory volume in the first second
(FEV1) = 60%, dyspnea at rest or requiring oxygen or any pleural neoplasm (Transient
use of supplemental oxygen is allowed.)

- Subject has active hepatitis B or C or other active hepatic disorder.

- Subjects with positive hepatitis B surface antigen (HBsAg) or detectable
hepatitis B DNA are not eligible.

- Subjects with negative HBsAg, positive hepatitis B core antibody and negative
hepatitis B surface antibody will be eligible if hepatitis B DNA is undetectable.

- Subjects with antibodies to hepatitis C virus will be eligible if hepatitis C RNA
is undetectable

- Subject has any condition which makes the subject unsuitable for study participation,
including any contraindications of azacitidine.

- Subject has a known or suspected hypersensitivity to ASP2215, azacitidine or any
components of the formulations used.

- [US Only]: Subject is = 65 to 74 years of age, suitable for and willing to receive
intensive induction chemotherapy.

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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Site AU61004 - Liverpool
Recruitment hospital [2] 0 0
Site AU61008 - Adelaide
Recruitment hospital [3] 0 0
Site AU61007 - Geelong
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
SA 5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3220 - Geelong
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
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
New Jersey
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
South Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Utah
Country [8] 0 0
Belgium
State/province [8] 0 0
Bruxelles-Capitale, Region De
Country [9] 0 0
Belgium
State/province [9] 0 0
Bruxelles
Country [10] 0 0
Belgium
State/province [10] 0 0
Gent
Country [11] 0 0
Canada
State/province [11] 0 0
Alberta
Country [12] 0 0
Canada
State/province [12] 0 0
Ontario
Country [13] 0 0
Canada
State/province [13] 0 0
Quebec
Country [14] 0 0
France
State/province [14] 0 0
Gard
Country [15] 0 0
France
State/province [15] 0 0
Gironde
Country [16] 0 0
France
State/province [16] 0 0
Haute-Normandie
Country [17] 0 0
France
State/province [17] 0 0
Herault
Country [18] 0 0
France
State/province [18] 0 0
Ille-et-Vilaine
Country [19] 0 0
France
State/province [19] 0 0
Loire-Atlantique
Country [20] 0 0
France
State/province [20] 0 0
Nord
Country [21] 0 0
France
State/province [21] 0 0
Rhone
Country [22] 0 0
France
State/province [22] 0 0
Sarthe
Country [23] 0 0
France
State/province [23] 0 0
Vienne
Country [24] 0 0
France
State/province [24] 0 0
Angers
Country [25] 0 0
France
State/province [25] 0 0
Bayonne
Country [26] 0 0
France
State/province [26] 0 0
Lille cedex
Country [27] 0 0
France
State/province [27] 0 0
Lille
Country [28] 0 0
Germany
State/province [28] 0 0
Baden-Wurttemberg
Country [29] 0 0
Germany
State/province [29] 0 0
Bayern
Country [30] 0 0
Germany
State/province [30] 0 0
Hessen
Country [31] 0 0
Germany
State/province [31] 0 0
Mecklenburg-Vorpommern
Country [32] 0 0
Germany
State/province [32] 0 0
Niedersachsen
Country [33] 0 0
Germany
State/province [33] 0 0
Sachsen-Anhalt
Country [34] 0 0
Germany
State/province [34] 0 0
Berlin
Country [35] 0 0
Germany
State/province [35] 0 0
Stuttgart
Country [36] 0 0
Italy
State/province [36] 0 0
Ancona
Country [37] 0 0
Italy
State/province [37] 0 0
Bologna
Country [38] 0 0
Italy
State/province [38] 0 0
Firenze
Country [39] 0 0
Italy
State/province [39] 0 0
Milano
Country [40] 0 0
Italy
State/province [40] 0 0
Monza
Country [41] 0 0
Italy
State/province [41] 0 0
Napoli
Country [42] 0 0
Italy
State/province [42] 0 0
Novara
Country [43] 0 0
Italy
State/province [43] 0 0
Palermo
Country [44] 0 0
Italy
State/province [44] 0 0
Pavia
Country [45] 0 0
Italy
State/province [45] 0 0
San Giovanni Rotondo
Country [46] 0 0
Japan
State/province [46] 0 0
Aichi
Country [47] 0 0
Japan
State/province [47] 0 0
Ehime
Country [48] 0 0
Japan
State/province [48] 0 0
Hiroshima
Country [49] 0 0
Japan
State/province [49] 0 0
Hokkaido
Country [50] 0 0
Japan
State/province [50] 0 0
Hyogo
Country [51] 0 0
Japan
State/province [51] 0 0
Ibaraki
Country [52] 0 0
Japan
State/province [52] 0 0
Ishikawa
Country [53] 0 0
Japan
State/province [53] 0 0
Kanagawa
Country [54] 0 0
Japan
State/province [54] 0 0
Miyagi
Country [55] 0 0
Japan
State/province [55] 0 0
Okayama
Country [56] 0 0
Japan
State/province [56] 0 0
Tokyo
Country [57] 0 0
Japan
State/province [57] 0 0
Chiba
Country [58] 0 0
Japan
State/province [58] 0 0
Fukuoka
Country [59] 0 0
Japan
State/province [59] 0 0
Gifu
Country [60] 0 0
Japan
State/province [60] 0 0
Kumamoto
Country [61] 0 0
Japan
State/province [61] 0 0
Kyoto
Country [62] 0 0
Japan
State/province [62] 0 0
Nagasaki
Country [63] 0 0
Japan
State/province [63] 0 0
Osaka
Country [64] 0 0
Japan
State/province [64] 0 0
Tokushima
Country [65] 0 0
Japan
State/province [65] 0 0
Toyama
Country [66] 0 0
Korea, Republic of
State/province [66] 0 0
Incheon Gwang'yeogsiv
Country [67] 0 0
Korea, Republic of
State/province [67] 0 0
Seoul Teugbyeolsi
Country [68] 0 0
Korea, Republic of
State/province [68] 0 0
Ulsan Gwang'yeogsi
Country [69] 0 0
Korea, Republic of
State/province [69] 0 0
Busan
Country [70] 0 0
Korea, Republic of
State/province [70] 0 0
Hwasun-gun
Country [71] 0 0
Korea, Republic of
State/province [71] 0 0
Seongnam-si
Country [72] 0 0
Korea, Republic of
State/province [72] 0 0
Seoul
Country [73] 0 0
Poland
State/province [73] 0 0
Lubelskie
Country [74] 0 0
Poland
State/province [74] 0 0
Mazowieckie
Country [75] 0 0
Poland
State/province [75] 0 0
Opolskie
Country [76] 0 0
Poland
State/province [76] 0 0
Warminsko-mazurskie
Country [77] 0 0
Spain
State/province [77] 0 0
Asturias
Country [78] 0 0
Spain
State/province [78] 0 0
Baleares
Country [79] 0 0
Spain
State/province [79] 0 0
Barcelona
Country [80] 0 0
Spain
State/province [80] 0 0
Caceres
Country [81] 0 0
Spain
State/province [81] 0 0
Madrid
Country [82] 0 0
Spain
State/province [82] 0 0
Valencia
Country [83] 0 0
Taiwan
State/province [83] 0 0
Kaohsiung
Country [84] 0 0
Taiwan
State/province [84] 0 0
Kwei Shan Hsiang
Country [85] 0 0
Taiwan
State/province [85] 0 0
Tainan
Country [86] 0 0
Taiwan
State/province [86] 0 0
Taipei
Country [87] 0 0
United Kingdom
State/province [87] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Astellas Pharma Global Development, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a clinical study for adult patients who have recently been diagnosed with acute
myeloid leukemia or AML. AML is a type of cancer. It is when bone marrow makes white blood
cells that are not normal. These are called leukemia cells. Some patients with AML have a
mutation, or change, in the FLT3 gene. This gene helps leukemia cells make a protein called
FLT3. This protein causes the leukemia cells to grow faster.

For patients with AML who cannot receive standard chemotherapy, azacitidine (also known as
Vidaza®) is a current standard of care treatment option in the United States. This clinical
study is testing an experimental medicine called ASP2215, also known as gilteritinib.
Gilteritinib works by stopping the leukemia cells from making the FLT3 protein. This can help
stop the leukemia cells from growing faster.

This study will compare two different treatments. Patients are assigned to one of these two
groups by chance: a medicine called azacitidine, also known as Vidaza®, or an experimental
medicine gilteritinib in combination with azacitidine. There is a twice as much chance to
receive both medicines combined than azacitidine alone. The clinical study may help show
which treatment helps patients live longer.
Trial website
https://clinicaltrials.gov/show/NCT02752035
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Astellas Pharma Global Development, Inc.
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

Summary results
Other publications