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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02997202




Registration number
NCT02997202
Ethics application status
Date submitted
1/12/2016
Date registered
19/12/2016

Titles & IDs
Public title
A Trial of the FMS-like Tyrosine Kinase 3 (FLT3) Inhibitor Gilteritinib Administered as Maintenance Therapy Following Allogeneic Transplant for Patients With FLT3/Internal Tandem Duplication (ITD) Acute Myeloid Leukemia (AML)
Scientific title
A Multi-center, Randomized, Double-blind, Placebo-controlled Phase III Trial of the FLT3 Inhibitor Gilteritinib Administered as Maintenance Therapy Following Allogeneic Transplant for Patients With FLT3/ITD AML
Secondary ID [1] 0 0
2016-001061-83
Secondary ID [2] 0 0
2215-CL-0304
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia 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 will take gilteritinib once daily for continuous daily dosing.

Placebo comparator: Placebo - Participants will take placebo once daily for continuous daily dosing.


Treatment: Drugs: gilteritinib
oral

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

Outcomes
Primary outcome [1] 0 0
Relapse-free survival
Timepoint [1] 0 0
96 months
Secondary outcome [1] 0 0
Safety and tolerability assessed by incidence and severity of adverse events
Timepoint [1] 0 0
25 months (24 months + 30 days)
Secondary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
66 months (5.5 years)
Secondary outcome [3] 0 0
Non-relapse Mortality
Timepoint [3] 0 0
66 months (5.5 years)
Secondary outcome [4] 0 0
Event-free Survival (EFS) at 12 months
Timepoint [4] 0 0
12 months
Secondary outcome [5] 0 0
Event-free Survival (EFS) at 24 months
Timepoint [5] 0 0
24 months
Secondary outcome [6] 0 0
Cumulative Incidence of Acute Graft vs. Host Disease (GVHD)
Timepoint [6] 0 0
6 months
Secondary outcome [7] 0 0
Cumulative Incidence of Chronic GVHD at 12 months
Timepoint [7] 0 0
12 months
Secondary outcome [8] 0 0
Cumulative Incidence of Chronic GVHD at 24 months
Timepoint [8] 0 0
24 months
Secondary outcome [9] 0 0
The cumulative incidence of detection of FLT3/ITD MRD
Timepoint [9] 0 0
24 months
Secondary outcome [10] 0 0
Incidence of Severity of Infection
Timepoint [10] 0 0
25 months (24 months + 30 days)

Eligibility
Key inclusion criteria
Registration Inclusion Criteria

* Participant is considered a suitable candidate for HCT and has an acceptable source of allogeneic donor stem cells, as defined per institutional practice (allogeneic HCT for any donor source [matched sibling, unrelated donor (URD), mismatched URD, related haploidentical, or umbilical cord blood] and any graft source [umbilical cord, BM, peripheral blood (PB)], and any conditioning [myeloablative conditioning (MAC), reduced intensity conditioning (RIC), or non-myeloablative conditioning (NMA)] will be permitted).
* Participant is considered a legal adult by local regulation at the time of signing informed consent form (ICF).
* Participant consents to allow access to diagnostic BM aspirate or PB sample and/or the DNA derived from that sample, if available, that may be used to validate a companion diagnostic that is being developed in parallel with gilteritinib.
* Participant has confirmed, morphologically documented AML in CR1. For the purposes of registration, CR1 will be defined as < 5% blasts in the BM with no morphologic characteristics of acute leukemia (e.g., Auer Rods) in the BM with no evidence of extramedullary disease such as central nervous system involvement or granulocytic sarcoma.

* Participant has not received more than 2 cycles of induction chemotherapy to achieve CR1. The induction cycles can be the same regimen or different regimens. The regimen(s) may contain conventional agents, investigational agents, or a combination of both.
* Participants with CR with incomplete count recovery (CRp or CRi) are allowed. Incomplete platelet recovery (CRp) is defined as CR with platelet count < 100 x 109/L. Incomplete blood count recovery (CRi) is defined as CR with residual neutropenia < 1 x 109/L with or without complete platelet recovery. Red blood cell count (RBC) and platelet transfusion independence is not required.
* The maximum time allowed from establishment of CR1 to registration is 12 months.
* Participant has presence of the FLT3/ITD activating mutation in the BM or PB as determined by the local institution at diagnosis.
* Participant must meet the following criteria as indicated on the clinical laboratory tests:

* Serum creatinine within normal range, or if serum creatinine outside normal range, then glomerular filtration rate (GFR) > 40 mL/min/1.73m2 as calculated with the Cockcroft-Gault equation with adjustment if total body weight is = 125% of ideal body weight.
* Total bilirubin (TBL) = 2.5 mg/dL, except for participants with Gilbert's syndrome.
* Serum AST and/or alanine aminotransferase (ALT) < 3 x institutional upper limit of normal (ULN).
* Participant has left ventricular ejection fraction at rest = 40%.
* Participant has diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) = 50% predicted and/or forced expiratory volume in 1 second (FEV1) = 50% predicted.
* Female participants must either:

* Be of non-childbearing potential:
* postmenopausal (defined as at least 1 year without menses) prior to screening or
* documented as surgically sterilized (at least 1 month prior to the screening visit)
* Or, if of childbearing potential,

* Agree not to try to become pregnant during the study for 6 months after the final study drug administration
* And have a negative 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.
* For United Kingdom sites:
* Highly effective forms of birth control include:
* Consistent and correct usage of established hormonal contraceptives that inhibit ovulation
* Established intrauterine device (IUD) or intrauterine system (IUS)
* Female participants must agree not to breastfeed or donate ova throughout the study drug treatment period and for 6 months after the final study drug administration.
* Male participants (even if surgically sterilized), and partners who are women of childbearing potential must be using highly effective contraception in addition to a barrier method throughout the study drug treatment period and for 127 days after the final study drug administration.

* For United Kingdom sites:
* Highly effective forms of birth control include:
* Consistent and correct usage of established hormonal contraceptives that inhibit ovulation
* Established IUD or IUS
* Vasectomy (A vasectomy is a highly effective contraception method provided the absence of sperm has been confirmed. If not, an additional highly effective method of contraception should be used.)
* Male is sterile due to a bilateral orchiectomy
* Male participants must not donate sperm throughout the study drug treatment period and for 127 days after the final study drug administration.
* Participant is able to take an oral medication.
* Participant agrees not to participate in another interventional study while on treatment.

Randomization Inclusion Criteria

* Participant is = 30 days and = 90 days from hematopoietic cell infusion.
* Participant has achieved engraftment. Engraftment is defined as ANC = 500 cells/µL and platelets = 20000/µL on 3 consecutive measurements (each occurring at least 1 day apart). The participant must not have had a platelet transfusion within 7 days prior to the first measurement.
* Participant has confirmed ongoing morphologically documented AML in CR1. For the purposes of randomization, CR1 will be defined as < 5% blasts with no morphologic characteristics of acute leukemia (e.g., Auer Rods) in the BM with no evidence of extramedullary disease such as central nervous system involvement or granulocytic sarcoma.
* Participant meets the following criteria as indicated on the clinical laboratory tests:

* Serum creatinine within normal range, or if serum creatinine outside normal range, then GFR > 40 mL/min/1.73m2 as calculated with the Cockcroft-Gault equation with adjustment if total body weight is = 125% of ideal body weight.
* TBL < 2.5 mg/dL, except for participants with Gilbert's syndrome.
* Serum AST and/or ALT < 3 x institutional ULN.
* Serum potassium and magnesium = the institutional lower limit of normal (LLN).
* If the participant has developed overall grades II-IV acute GVHD, the following criteria must be met to be randomized:

* No requirement of > 0.5 mg/kg of prednisone (or equivalent) daily dose within 1 week of randomization
* No escalation of systemic immunosuppression in terms of increase of corticosteroids or addition of new agent / modality within 2 weeks of randomization. (Note that increasing calcineurin inhibitors or sirolimus to achieve therapeutic trough levels is allowed.) Topical skin and topical gastrointestinal steroids are allowed.
* Participant is able to take oral medication.

Registration
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

* Participant has had a prior allogeneic transplant.
* Participant has Karnofsky performance status score < 70% .
* Participant requires treatment with concomitant drugs that are strong inducers of CYP3A within 14 days of start of study drug.
* Participant 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 participant.
* Participant has a Fridericia-corrected QT interval (QTcF) > 450 msec (average of triplicate determinations) per central read.
* Participant has long QT Syndrome at screening.
* Participant has a known infection with human immunodeficiency virus (HIV).
* Participant has active hepatitis B infection as determined by NAAT or surface antigen assay. Participants who have acquired immunity from past exposure (HBcAb positive / HBsAb positive / HBsAg negative) are eligible.
* Participant has active hepatitis C infection as determined by NAAT. NAAT must be performed if the participant has positive serology for hepatitis C. Participants who have had past exposure and have no detectable virus either through spontaneous clearance or treatment are eligible.
* Participant has an uncontrolled infection. If a bacterial or viral infection is present, the participant must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to registration. If a fungal infection is present, the participant must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to registration.

* Progressing infection is 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.
* Participant has had a myocardial infarction within 6 months prior to registration or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia.
* Participant has a serious medical or psychiatric illness likely to interfere with participation in this clinical study.
* Participant is breast feeding or pregnant.
* Participant has prior malignancies, except lobular breast carcinoma in situ, fully resected basal cell or squamous cell carcinoma of skin 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.

Randomization Exclusion Criteria

* Participant requires treatment with concomitant drugs that are strong inducers of CYP3A within 14 days of starting study drug.
* Participant requires treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR or sigma nonspecific receptor with the exception of drugs that are considered by the investigator to be absolutely essential for the care of the participant and for which no acceptable alternative exists.
* Participant has a QTcF interval > 450 msec (average of triplicate determinations) by central read.
* Participant has a need for supplemental oxygen with the exception of using previously existing non-invasive continuous positive airway pressure (CPAP) at night.
* Participant has used investigational agents within 4 weeks of randomization.
* Participant has used experimental therapy for acute GVHD within 4 weeks of randomization. If unsure of the definition of "experimental", discussion with one of the protocol chairs is recommended.
* Participant has an uncontrolled infection. If a bacterial or viral infection is present, the participant 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 participant must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to randomization.

* Progressing infection is 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.

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 administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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
16/08/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/05/2023
Sample size
Target
Accrual to date
Final
356
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Site AU61001 - Liverpool
Recruitment hospital [2] 0 0
Site AU61002 - Melbourne
Recruitment hospital [3] 0 0
Site AU61004 - Westmead
Recruitment postcode(s) [1] 0 0
- Liverpool
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment postcode(s) [3] 0 0
- Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
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Indiana
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United States of America
State/province [9] 0 0
Kansas
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United States of America
State/province [10] 0 0
Maryland
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United States of America
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Massachusetts
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United States of America
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Michigan
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Minnesota
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United States of America
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Missouri
Country [15] 0 0
United States of America
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Nebraska
Country [16] 0 0
United States of America
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New York
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United States of America
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North Carolina
Country [18] 0 0
United States of America
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Ohio
Country [19] 0 0
United States of America
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Oregon
Country [20] 0 0
United States of America
State/province [20] 0 0
Pennsylvania
Country [21] 0 0
United States of America
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Tennessee
Country [22] 0 0
United States of America
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Texas
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United States of America
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Utah
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United States of America
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Washington
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United States of America
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West Virginia
Country [26] 0 0
United States of America
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Wisconsin
Country [27] 0 0
Belgium
State/province [27] 0 0
Bruxelles
Country [28] 0 0
Belgium
State/province [28] 0 0
Gent
Country [29] 0 0
Canada
State/province [29] 0 0
Hamilton
Country [30] 0 0
Canada
State/province [30] 0 0
Montreal
Country [31] 0 0
Denmark
State/province [31] 0 0
Arhus
Country [32] 0 0
Denmark
State/province [32] 0 0
Copenhagen
Country [33] 0 0
France
State/province [33] 0 0
Lille
Country [34] 0 0
France
State/province [34] 0 0
Lyon
Country [35] 0 0
France
State/province [35] 0 0
Paris
Country [36] 0 0
France
State/province [36] 0 0
Pessac
Country [37] 0 0
France
State/province [37] 0 0
Vandoeuvre-Les-Nancy
Country [38] 0 0
Germany
State/province [38] 0 0
Düsseldorf
Country [39] 0 0
Germany
State/province [39] 0 0
Halle (Saale)
Country [40] 0 0
Germany
State/province [40] 0 0
Hamburg
Country [41] 0 0
Germany
State/province [41] 0 0
Köln
Country [42] 0 0
Germany
State/province [42] 0 0
Mainz
Country [43] 0 0
Germany
State/province [43] 0 0
Münster
Country [44] 0 0
Greece
State/province [44] 0 0
Athens
Country [45] 0 0
Greece
State/province [45] 0 0
Rio
Country [46] 0 0
Greece
State/province [46] 0 0
Thessaloniki
Country [47] 0 0
Italy
State/province [47] 0 0
Bergamo
Country [48] 0 0
Italy
State/province [48] 0 0
Bologna
Country [49] 0 0
Italy
State/province [49] 0 0
Genova
Country [50] 0 0
Italy
State/province [50] 0 0
Milano
Country [51] 0 0
Italy
State/province [51] 0 0
Pescara
Country [52] 0 0
Italy
State/province [52] 0 0
Roma
Country [53] 0 0
Italy
State/province [53] 0 0
Udine
Country [54] 0 0
Japan
State/province [54] 0 0
Aichi
Country [55] 0 0
Japan
State/province [55] 0 0
Hokkaido
Country [56] 0 0
Japan
State/province [56] 0 0
Hyogo
Country [57] 0 0
Japan
State/province [57] 0 0
Kanagawa
Country [58] 0 0
Japan
State/province [58] 0 0
Miyagi
Country [59] 0 0
Japan
State/province [59] 0 0
Osaka
Country [60] 0 0
Japan
State/province [60] 0 0
Tochigi
Country [61] 0 0
Japan
State/province [61] 0 0
Tokyo
Country [62] 0 0
Japan
State/province [62] 0 0
Fukuoka
Country [63] 0 0
Japan
State/province [63] 0 0
Kyoto
Country [64] 0 0
Japan
State/province [64] 0 0
Okayama
Country [65] 0 0
Korea, Republic of
State/province [65] 0 0
Seoul
Country [66] 0 0
New Zealand
State/province [66] 0 0
Christchurch
Country [67] 0 0
New Zealand
State/province [67] 0 0
Grafton
Country [68] 0 0
Poland
State/province [68] 0 0
Warszawa
Country [69] 0 0
Spain
State/province [69] 0 0
Barcelona
Country [70] 0 0
Spain
State/province [70] 0 0
Salamanca
Country [71] 0 0
Spain
State/province [71] 0 0
Santander
Country [72] 0 0
Spain
State/province [72] 0 0
Valencia
Country [73] 0 0
Taiwan
State/province [73] 0 0
Taichung
Country [74] 0 0
Taiwan
State/province [74] 0 0
Taipei
Country [75] 0 0
Taiwan
State/province [75] 0 0
Taoyuan
Country [76] 0 0
United Kingdom
State/province [76] 0 0
Birmingham
Country [77] 0 0
United Kingdom
State/province [77] 0 0
Bristol
Country [78] 0 0
United Kingdom
State/province [78] 0 0
Glasgow
Country [79] 0 0
United Kingdom
State/province [79] 0 0
London
Country [80] 0 0
United Kingdom
State/province [80] 0 0
Manchester
Country [81] 0 0
United Kingdom
State/province [81] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Astellas Pharma Global Development, Inc.
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Heart, Lung, and Blood Institute (NHLBI)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Blood and Marrow Transplant Clinical Trials Network
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Senior 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: http://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 are available at https://clinicaltrials.gov/study/NCT02997202