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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02752035
Ethics application status
Date submitted
22/04/2016
Date registered
26/04/2016

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)
Timepoint [1] 0 0
Up to 77 months
Secondary outcome [1] 0 0
Event free survival (EFS)
Timepoint [1] 0 0
Up to 77 months
Secondary outcome [2] 0 0
Best response
Timepoint [2] 0 0
Up to 48 months
Secondary outcome [3] 0 0
Complete remission (CR) rate
Timepoint [3] 0 0
Up to 48 months
Secondary outcome [4] 0 0
Composite complete remission (CRc) rate
Timepoint [4] 0 0
Up to 48 months
Secondary outcome [5] 0 0
Complete remission with partial hematologic recovery (CRh) rate
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
Timepoint [6] 0 0
Up to 48 months
Secondary outcome [7] 0 0
Transfusion conversion rate
Timepoint [7] 0 0
Up to 49 months
Secondary outcome [8] 0 0
Transfusion maintenance rate
Timepoint [8] 0 0
Up to 49 months
Secondary outcome [9] 0 0
Leukemia free survival (LFS)
Timepoint [9] 0 0
Up to 77 months
Secondary outcome [10] 0 0
Duration of remission
Timepoint [10] 0 0
Up to 48 months
Secondary outcome [11] 0 0
Participant reported fatigue from Brief Fatigue Inventory (BFI)
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
Timepoint [15] 0 0
Up to 48 months
Secondary outcome [16] 0 0
Safety assessed by electrocardiograms (ECGs)
Timepoint [16] 0 0
Up to 48 months
Secondary outcome [17] 0 0
Eastern Cooperative Oncology Group (ECOG) performance status score
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
Sex
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
1/08/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2024
Actual
Sample size
Target
Accrual to date
Final
183
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
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
Available to whom?
Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.clinicalstudydatarequest.com/


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02752035