Trial Review

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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/NCT02927262




Registration number
NCT02927262
Ethics application status
Date submitted
5/10/2016
Date registered
7/10/2016
Date last updated
27/10/2023

Titles & IDs
Public title
A Study of ASP2215 (Gilteritinib), Administered as Maintenance Therapy Following Induction/Consolidation Therapy for Subjects With FMS-like Tyrosine Kinase 3 (FLT3/ITD) Acute Myeloid Leukemia (AML) in First Complete Remission
Scientific title
A Phase 2 Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of the FLT3 Inhibitor Gilteritinib (ASP2215) Administered as Maintenance Therapy Following Induction/Consolidation Therapy for Subjects With FLT3/ITD AML in First Complete Remission
Secondary ID [1] 0 0
2016-001643-39
Secondary ID [2] 0 0
2215-CL-0302
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) / Internal Tandem Duplication (ITD) 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 - Placebo

Experimental: Gilteritinib - Participants received gilteritinib 120 mg (three tablets of 40 mg) orally, once daily (QD) for up to 2 years or until a protocol-specified discontinuation criterion was met.

Placebo Comparator: Placebo - Participants received gilteritinib matching placebo orally, QD for up to 2 years or until a protocol-specified discontinuation criterion was met.


Treatment: Drugs: Gilteritinib
Oral tablet

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

Outcomes
Primary outcome [1] 0 0
Relapse-free Survival (RFS) Per Independent Review Committee (IRC) Adjudication
Timepoint [1] 0 0
From the date of randomization until the date of documented relapse, or death; (Median time on study drug was 427 days for gilteritinib group and 212 days for placebo group)
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
From the date of randomization until the date of death from any cause; (Median time on study drug was 427 days for gilteritinib group and 212 days for placebo group)
Secondary outcome [2] 0 0
Event-Free Survival (EFS)
Timepoint [2] 0 0
From date of randomization until the date of documented relapse or discontinuation of the treatment, or initiation of other anti-leukemic treatment or death from any cause; (Median time on study drug was 427 days for gilteritinib and 212 days for Placebo)
Secondary outcome [3] 0 0
Change From Baseline in Quantitative Minimal Residual Disease Measured as Log10-transformed Overall FLT3/ITD Mutation Ratio at Months 3, 6, 12, 24/End of Treatment (EoT)
Timepoint [3] 0 0
Baseline and months 3, 6, 12, 24/EoT
Secondary outcome [4] 0 0
Number of Participants With Adverse Events (AE)
Timepoint [4] 0 0
From first dose date up to 30 days after last dose or data cut-off date 25-May 2021 (Maximum treatment duration was 744 days)
Secondary outcome [5] 0 0
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Score
Timepoint [5] 0 0
Months 1, 2, 3, 4, 5, 6, 8, 10. 12, 14, 16, 18, 20, 22 and 24/EoT

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

- Subject consents to allow access to subject's diagnostic bone marrow aspirate or
peripheral blood sample and/or the DNA derived from that sample, if available, that
may be used to validate a companion diagnostic test for gilteritinib.

- Subject has confirmed morphologically documented AML, excluding acute promyelocytic
leukemia (APL), in CR1 (including CRp and CRi). For the purposes of enrollment, CR
will be defined as < 5% blasts in the bone marrow with no morphologic characteristics
of acute leukemia (e.g., Auer rods) in the bone marrow with no evidence of
extramedullary disease such as central nervous system involvement or granulocytic
sarcoma.

- Subject will not proceed with transplantation as either a decision not to proceed with
transplantation has been made either on the recommendation of the treating physician
or by the patient or a suitable donor could not be identified.

- Subject is < 2 months from the start of the last cycle of consolidation and should
have completed the recommended number of consolidations per local practice.

- Subject has had no use of investigational agents, with the exception of FLT3
inhibiting agents during induction and/or consolidation therapy, within the prior 4
weeks.

- Subject has had presence of the FLT3/ITD activating mutation in the bone marrow or
peripheral blood as determined by the local institution at diagnosis.

- Subject has an ECOG performance status 0 to 2.

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

- Serum creatinine = 1.5 x institutional upper limit of normal (ULN), or if serum
creatinine outside normal range, then glomerular filtration rate (GFR) > 40
mL/min/1.73m^2 as calculated with the 4-parameter Modification of Diet in Renal
Disease (MDRD) equation.

- Serum total bilirubin = 2.5 mg/dL (43 µmol/L), except for subjects with Gilbert's
syndrome.

- Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x
ULN.

- Serum potassium and serum magnesium = institutional lower limit of normal (LLN).

- Absolute neutrophil count (ANC) = 500/µl and platelets = 20000/µl (unsupported by
transfusions).

- Subject is suitable for oral administration of study drug.

- Female subject must either:

- Be of nonchildbearing potential:

- Postmenopausal (defined as at least 1 year without any menses) prior to
screening, or

- Documented surgically sterile or status posthysterectomy (at least 1 month prior
to screening)

- Or, if of childbearing potential,

- Agree not to try to become pregnant during the study and for 6 months after the
final study drug administration

- And have a negative urine or serum pregnancy test at screening

- And, if heterosexually active, agree to consistently use highly effective
contraception per locally accepted standards (in addition to a barrier method)
starting at screening and throughout the study period and for 6 months after the
final study drug administration.

- Female subject must agree not to breastfeed starting at screening and throughout the
study period, and for 2 months and 1 week after the final study drug administration.

- Female subject must not donate ova starting at screening and throughout the study
period, and for 6 months after the final study drug administration.

- Male subject and subject's female partners who are of childbearing potential must be
using highly effective contraception per locally accepted standards (in addition to a
barrier method) starting at screening and continue throughout the study period and for
4 months and 1 week after the final study drug administration.

- Male subject must not donate sperm starting at screening and throughout the study
period and for 4 months and 1 week 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
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Subject has had prior allogeneic transplant.

- Subject has QTcF interval > 450 msec (average of triplicate determinations based on
central reading).

- Subject with Long QT Syndrome.

- Subject with hypokalemia and hypomagnesemia at screening (defined as values below
LLN).

- Subject has clinically active central nervous system leukemia.

- Subject is known to have human immunodeficiency virus infection.

- Subject has active hepatitis B or C.

- Subject has an uncontrolled infection. If a bacterial or viral infection is present,
the subject must be receiving definitive therapy and have no signs of progressing
infection for 72 hours prior to randomization. If a fungal infection is present, the
subject must be receiving definitive systemic anti-fungal therapy and have no signs of
progressing infection for 1 week prior to randomization.

- Subject has progressing infection defined as hemodynamic instability attributable to
sepsis or new symptoms, worsening physical signs or radiographic findings attributable
to infection. Persisting fever without other signs or symptoms will not be interpreted
as progressing infection.

- Subject has uncontrolled angina, severe uncontrolled ventricular arrhythmias,
electrocardiographic evidence of acute ischemia, congestive heart failure New York
Heart Association (NYHA) class 3 or 4 or subject has a history of congestive heart
failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multigated
acquisition (MUGA) scan performed within 1 month prior to study entry results in a
left ventricular ejection fraction that is = 45%.

- Subject requires treatment with concomitant drugs that are strong inducers of
cytochrome P450 (CYP) 3A.

- Subject requires treatment with concomitant drugs that are strong inhibitors or
inducers of P-glycoprotein (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 1 (5HT1R) or 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 a serious medical or psychiatric illness likely to interfere with
participation in this clinical study.

- Subject has prior malignancies, except resected basal cell carcinoma or treated
cervical carcinoma in situ. Cancer treated with curative intent = 5 years previously
will be allowed. Cancer treated with curative intent < 5 years previously will not be
allowed.

- Subject has any condition which makes the subject unsuitable for study participation.

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
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
10/01/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
29/02/2024
Actual
Sample size
Target
Accrual to date
Final
98
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
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
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Oregon
Country [5] 0 0
United States of America
State/province [5] 0 0
South Carolina
Country [6] 0 0
Brazil
State/province [6] 0 0
Goias
Country [7] 0 0
Canada
State/province [7] 0 0
Nova Scotia
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
Czechia
State/province [9] 0 0
Ostrava-Poruba
Country [10] 0 0
Denmark
State/province [10] 0 0
Region Midtjylland
Country [11] 0 0
France
State/province [11] 0 0
Finistere
Country [12] 0 0
France
State/province [12] 0 0
Indre-et-Loire
Country [13] 0 0
France
State/province [13] 0 0
Meurthe-et-Moselle
Country [14] 0 0
France
State/province [14] 0 0
Rhone
Country [15] 0 0
France
State/province [15] 0 0
Bayonne
Country [16] 0 0
France
State/province [16] 0 0
Mulhouse
Country [17] 0 0
France
State/province [17] 0 0
Nice Cedex 2
Country [18] 0 0
Germany
State/province [18] 0 0
Nordrhein-Westfalen
Country [19] 0 0
Germany
State/province [19] 0 0
Stuttgart
Country [20] 0 0
Greece
State/province [20] 0 0
Attiki
Country [21] 0 0
Greece
State/province [21] 0 0
Kentriki Makedonia
Country [22] 0 0
Greece
State/province [22] 0 0
Athens
Country [23] 0 0
Greece
State/province [23] 0 0
Larissa
Country [24] 0 0
Hungary
State/province [24] 0 0
Szabolcs-Szatmar-Bereg
Country [25] 0 0
Israel
State/province [25] 0 0
Yerushalayim
Country [26] 0 0
Italy
State/province [26] 0 0
Lombardia
Country [27] 0 0
Italy
State/province [27] 0 0
Treviso
Country [28] 0 0
Italy
State/province [28] 0 0
Bergamo
Country [29] 0 0
Italy
State/province [29] 0 0
Parma
Country [30] 0 0
Italy
State/province [30] 0 0
Reggio Emilia
Country [31] 0 0
Italy
State/province [31] 0 0
Roma
Country [32] 0 0
Japan
State/province [32] 0 0
Aichi
Country [33] 0 0
Japan
State/province [33] 0 0
Ehime
Country [34] 0 0
Japan
State/province [34] 0 0
Fukui
Country [35] 0 0
Japan
State/province [35] 0 0
Hokkaido
Country [36] 0 0
Japan
State/province [36] 0 0
Hyogo
Country [37] 0 0
Japan
State/province [37] 0 0
Ishikawa
Country [38] 0 0
Japan
State/province [38] 0 0
Kanagawa
Country [39] 0 0
Japan
State/province [39] 0 0
Miyagi
Country [40] 0 0
Japan
State/province [40] 0 0
Tochigi
Country [41] 0 0
Japan
State/province [41] 0 0
Tokyo
Country [42] 0 0
Japan
State/province [42] 0 0
Aomori
Country [43] 0 0
Japan
State/province [43] 0 0
Okayama
Country [44] 0 0
Korea, Republic of
State/province [44] 0 0
Gyeonggi-do
Country [45] 0 0
Korea, Republic of
State/province [45] 0 0
Gyeonggido
Country [46] 0 0
Korea, Republic of
State/province [46] 0 0
Incheon Gwang'yeogsiv
Country [47] 0 0
Korea, Republic of
State/province [47] 0 0
Jeonranamdo
Country [48] 0 0
Korea, Republic of
State/province [48] 0 0
Seoul Teugbyeolsi
Country [49] 0 0
Korea, Republic of
State/province [49] 0 0
Busan
Country [50] 0 0
Korea, Republic of
State/province [50] 0 0
Seoul
Country [51] 0 0
Poland
State/province [51] 0 0
Warminsko-mazurskie
Country [52] 0 0
Poland
State/province [52] 0 0
Bydgoszcz
Country [53] 0 0
Poland
State/province [53] 0 0
Poznan
Country [54] 0 0
Portugal
State/province [54] 0 0
Coimbra
Country [55] 0 0
Portugal
State/province [55] 0 0
Porto
Country [56] 0 0
Romania
State/province [56] 0 0
Bucure?ti
Country [57] 0 0
Serbia
State/province [57] 0 0
Belgrade
Country [58] 0 0
Spain
State/province [58] 0 0
Alava
Country [59] 0 0
Sweden
State/province [59] 0 0
Stockholms Lan
Country [60] 0 0
Sweden
State/province [60] 0 0
Lund
Country [61] 0 0
Taiwan
State/province [61] 0 0
Kaohsiung
Country [62] 0 0
Taiwan
State/province [62] 0 0
Taipei
Country [63] 0 0
United Kingdom
State/province [63] 0 0
Devon
Country [64] 0 0
United Kingdom
State/province [64] 0 0
East Riding Of Yorkshire
Country [65] 0 0
United Kingdom
State/province [65] 0 0
London, City Of
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Birmingham
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Cardiff
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Leeds
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Nottingham

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

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study was to compare relapse-free survival (RFS) between participants
with FMS-like tyrosine kinase 3 (FLT3) / internal tandem duplication (ITD) acute myeloid
leukemia (AML) in first complete remission (CR1) and who were randomized to receive
gilteritinib or placebo beginning after completion of induction/consolidation chemotherapy
for a two-year period.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02927262
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Executive 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

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02927262