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

NCT ID: NCT02927262

Last Updated: 2024-11-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-10
• Study Completion Date: 2024-02-19

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.

Detailed Description

Participants in CR1 were approached for this study after induction/consolidation therapy was complete and a decision not to proceed with transplantation was made or a suitable donor could not be identified. Participants were randomized in a 2:1 ratio to receive gilteritinib or placebo. Participants entered the screening period up to 14 days prior to the start of treatment. Participants were administered treatment over continuous 28-day cycles. Gilteritinib or placebo was given daily for up to 2 years. After treatment discontinuation, participants had a 30-day follow-up visit for safety, after which the participants entered the long-term follow up period for collection of subsequent AML treatment, remission status, and survival (cause of death and date of death). Final database lock will occur when last subject last follow-up visit is reached, per protocol. Study drug was not provided during the follow-up period.

Conditions

Acute Myeloid Leukemia (AML); Acute Myeloid Leukemia With FMS-like Tyrosine Kinase (FLT3) / Internal Tandem Duplication (ITD) Mutation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Gilteritinib

Intervention Type: DRUG

Oral tablet

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Oral tablet

Interventions

Gilteritinib

Oral tablet

Intervention Type: DRUG

Placebo

Oral tablet

Intervention Type: DRUG

Other Intervention Names

ASP2215

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astellas Pharma Global Development, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Executive Medical Director

Role: STUDY_DIRECTOR

Astellas Pharma Global Development, Inc.

Locations

Site US10017

Gainesville, Florida, United States

Site US10030

Jacksonville, Florida, United States

Site US10012

Chicago, Illinois, United States

Site US10025

Syracuse, New York, United States

Site US10007

Portland, Oregon, United States

Site US10029

Greenville, South Carolina, United States

Site BR55002

Goiânia, Goiás, Brazil

Site CA15001

Halifax, Nova Scotia, Canada

Site CA15003

Toronto, Ontario, Canada

Site CZ42001

Ostrava-Poruba, , Czechia

Site DK45002

Aarhus, Central Jutland, Denmark

Site FR33004

Brest, Finistere, France

Site FR33002

Tours, Indre-et-Loire, France

Site FR33014

Vandœuvre-lès-Nancy, Meurthe-et-Moselle, France

Site FR33007

Pierre-Bénite, Rhone, France

Site FR33001

Bayonne, , France

Site FR33009

Mulhouse, , France

Site FR33008

Nice, , France

Site DE49001

Duisburg, North Rhine-Westphalia, Germany

Site DE49008

Stuttgart, , Germany

Site GR30010

Athens, Attica, Greece

Site GR30004

Thessaloniki, Central Macedonia, Greece

Site GR30009

Athens, , Greece

Site GR30007

Larissa, , Greece

Site HU36003

Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary

Site IL97205

Jerusalem, Jerusalem, Israel

Site IT39011

Milan, Lombardy, Italy

Site IT39004

Castelfranco Veneto (TV), Treviso, Italy

Site IT39008

Bergamo, , Italy

Site IT39005

Parma, , Italy

Site IT39010

Reggio Emilia, , Italy

Site IT39002

Roma, , Italy

Site JP81018

Nagoya, Aichi-ken, Japan

Site JP81025

Matsuyama, Ehime, Japan

Site JP81002

Yoshida-gun, Fukui, Japan

Site JP81024

Sapporo, Hokkaido, Japan

Site JP81012

Kobe, Hyōgo, Japan

Site JP81004

Kanazawa, Ishikawa-ken, Japan

Site JP81009

Yokohama, Kanagawa, Japan

Site JP81014

Sendai, Miyagi, Japan

Site JP81023

Shimotsuke, Tochigi, Japan

Site JP81011

Tachikawa, Tokyo, Japan

Site JP81010

Aomori, , Japan

Site JP81017

Okayama, , Japan

Site PL48001

Olsztyn, Warmian-Masurian Voivodeship, Poland

Site PL48002

Bydgoszcz, , Poland

Site PL48007

Poznan, , Poland

Site PT35106

Coimbra, , Portugal

Site PT35101

Porto, , Portugal

Site RO40005

Bucharest, , Romania

Site RS38102

Belgrade, , Serbia

Site KR82005

Suwon, Gyeonggi-do, South Korea

Site KR82014

Bucheon-si, Gyeonggido, South Korea

Site KR82013

Goyang, Gyeonggido, South Korea

Site KR82008

Namdong, Incheon Gwang'yeogsiv, South Korea

Site KR82003

Hwasungun, Jeonranamdo, South Korea

Site KR82012

Seoul, Seoul Teugbyeolsi, South Korea

Site KR82006

Busan, , South Korea

Site KR82009

Seoul, , South Korea

Site ES34009

Vitoria-Gasteiz, Alava, Spain

Site SE46003

Stockholm, Stockholm County, Sweden

Site SE46002

Lund, , Sweden

Site TW88605

Kaohsiung City, , Taiwan

Site TW88604

Kaohsiung City, , Taiwan

Site TW88603

Taipei, , Taiwan

Site GB44007

Exeter, Devon, United Kingdom

Site GB44019

Plymouth, Devon, United Kingdom

Site GB44006

Cottingham, East Riding Of Yorkshire, United Kingdom

Site GB44018

London, London, City of, United Kingdom

Site GB44002

Birmingham, , United Kingdom

Site GB44015

Cardiff, , United Kingdom

Site GB44020

Leeds, , United Kingdom

Site GB44004

Nottingham, , United Kingdom

Countries

United States; Brazil; Canada; Czechia; Denmark; France; Germany; Greece; Hungary; Israel; Italy; Japan; Poland; Portugal; Romania; Serbia; South Korea; Spain; Sweden; Taiwan; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-001643-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2215-CL-0302

Identifier Type: -

Identifier Source: org_study_id