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

NCT02927262 | Completed Phase 2 Results DMC

• 2 other identifiers: 2215-CL-03022016-001643-39
• Study Type: interventional
• Target: 98
• Locations: 20 countries
• Sites: 72

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.

Conditions

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

Keywords

Acute myeloid leukemia; First Complete Remission; gilteritinib; FLT3/ITD; AML; ASP2215

Outcome Measures

Primary Outcomes (1)

• Relapse-free Survival (RFS) Per Independent Review Committee (IRC) Adjudication

  RFS was defined as the time from the date of randomization until the date of documented relapse or death from any cause, whichever occurred first. Relapse after complete remission (CR) \[including complete remission with incomplete platelet recovery (CRp) and Complete remission with incomplete hematologic recovery (CRi)\], was defined as bone marrow blasts 5% or higher (not attributable to regenerating bone marrow), any circulating blasts, any extra-medullary blast foci as per Revised International Working Group (IWG) criteria. Participants were classified as: CRi, if they fulfilled all the criteria for CR except for incomplete hematological recovery with residual neutropenia \< 1 × 10\^9/L with or without complete platelet recovery. RBC and platelet transfusion independence was not required. CRp, if they achieved CR except for incomplete platelet recovery (\< 100 × 10\^9/L). RFS was estimated using Kaplan-Meier estimates. hazard ratio (HR), cox proportional hazards model (CHM)

  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 Outcomes (5)

• Overall Survival (OS)

  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)

• Event-Free Survival (EFS)

  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)

• 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)

  Baseline and months 3, 6, 12, 24/EoT

• Number of Participants With Adverse Events (AE)

  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)

• Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Score

  Months 1, 2, 3, 4, 5, 6, 8, 10. 12, 14, 16, 18, 20, 22 and 24/EoT

Study Arms (2)

Gilteritinib

EXPERIMENTAL

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.

Drug: Gilteritinib

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Gilteritinib DRUG

Oral tablet

Also known as: ASP2215

Gilteritinib

Placebo DRUG

Oral tablet

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (73)

Site US10017

Gainesville, Florida, 32610-0278, United States

Location

Site US10030

Jacksonville, Florida, 32204, United States

Location

Site US10012

Chicago, Illinois, 60612, United States

Location

Site US10025

Syracuse, New York, 13210, United States

Location

Site US10007

Portland, Oregon, 97239, United States

Location

Site US10029

Greenville, South Carolina, 26615, United States

Location

Site BR55002

Goiânia, Goiás, 74605-020, Brazil

Location

Site CA15001

Halifax, Nova Scotia, B3H2Y9, Canada

Location

Site CA15003

Toronto, Ontario, M5G 2M9, Canada

Location

Site CZ42001

Ostrava-Poruba, 70852, Czechia

Location

Site DK45002

Aarhus, Central Jutland, DK 8000, Denmark

Location

Site FR33004

Brest, Finistere, 29609, France

Location

Site FR33002

Tours, Indre-et-Loire, 37044, France

Location

Site FR33014

Vandœuvre-lès-Nancy, Meurthe-et-Moselle, 54511, France

Location

Site FR33007

Pierre-Bénite, Rhone, 69310, France

Location

Site FR33001

Bayonne, 64100, France

Location

Site FR33009

Mulhouse, 68070, France

Location

Site FR33008

Nice, 06189, France

Location

Site DE49001

Duisburg, North Rhine-Westphalia, 47166, Germany

Location

Site DE49008

Stuttgart, 70376, Germany

Location

Site GR30010

Athens, Attica, 10676, Greece

Location

Site GR30004

Thessaloniki, Central Macedonia, 57010, Greece

Location

Site GR30009

Athens, Greece

Location

Site GR30007

Larissa, Greece

Location

Site HU36003

Nyíregyháza, Szabolcs-Szatmár-Bereg, H-4400, Hungary

Location

Site IL97205

Jerusalem, Jerusalem, 91031, Israel

Location

Site IT39011

Milan, Lombardy, 20141, Italy

Location

Site IT39004

Castelfranco Veneto (TV), Treviso, 31033, Italy

Location

Site IT39008

Bergamo, 24127, Italy

Location

Site IT39005

Parma, Italy

Location

Site IT39010

Reggio Emilia, 42100, Italy

Location

Site IT39002

Roma, 161, Italy

Location

Site JP81018

Nagoya, Aichi-ken, Japan

Location

Site JP81025

Matsuyama, Ehime, Japan

Location

Site JP81002

Yoshida-gun, Fukui, Japan

Location

Site JP81024

Sapporo, Hokkaido, Japan

Location

Site JP81012

Kobe, Hyōgo, Japan

Location

Site JP81004

Kanazawa, Ishikawa-ken, Japan

Location

Site JP81009

Yokohama, Kanagawa, Japan

Location

Site JP81014

Sendai, Miyagi, Japan

Location

Site JP81023

Shimotsuke, Tochigi, Japan

Location

Site JP81011

Tachikawa, Tokyo, Japan

Location

Site JP81010

Aomori, Japan

Location

Site JP81017

Okayama, Japan

Location

Site PL48001

Olsztyn, Warmian-Masurian Voivodeship, 10-228, Poland

Location

Site PL48002

Bydgoszcz, 85-168, Poland

Location

Site PL48007

Poznan, Poland

Location

Site PT35106

Coimbra, 3000, Portugal

Location

Site PT35101

Porto, 4200-072, Portugal

Location

Site RO40005

Bucharest, Romania

Location

Site RS38102

Belgrade, 11000, Serbia

Location

Site KR82005

Suwon, Gyeonggi-do, 16499, South Korea

Location

Site KR82014

Bucheon-si, Gyeonggido, 14584, South Korea

Location

Site KR82013

Goyang, Gyeonggido, 10408, South Korea

Location

Site KR82008

Namdong, Incheon Gwang'yeogsiv, 405 760, South Korea

Location

Site KR82003

Hwasungun, Jeonranamdo, 58128, South Korea

Location

Site KR82012

Seoul, Seoul Teugbyeolsi, 06351, South Korea

Location

Site KR82006

Busan, 49241, South Korea

Location

Site KR82009

Seoul, 120-752, South Korea

Location

Site ES34009

Vitoria-Gasteiz, Alava, 01009, Spain

Location

Site SE46003

Stockholm, Stockholm County, 171 76, Sweden

Location

Site SE46002

Lund, 221 85, Sweden

Location

Site TW88605

Kaohsiung City, 112, Taiwan

Location

Site TW88604

Kaohsiung City, 83301, Taiwan

Location

Site TW88603

Taipei, 114, Taiwan

Location

Site GB44007

Exeter, Devon, EX2 5DW, United Kingdom

Location

Site GB44019

Plymouth, Devon, PL6 8DH, United Kingdom

Location

Site GB44006

Cottingham, East Riding Of Yorkshire, HU165JQ, United Kingdom

Location

Site GB44018

London, London, City of, WC1E 6BT, United Kingdom

Location

Site GB44002

Birmingham, B95SS, United Kingdom

Location

Site GB44015

Cardiff, CF4 4XN, United Kingdom

Location

Site GB44020

Leeds, LS9 7TF, United Kingdom

Location

Site GB44004

Nottingham, NG5 1PB, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

gilteritinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Clinical trial Disclosure
• Organization: Astellas Pharma Global Development, Inc

astellas.resultsdisclosure@astellas.com

800-888-7704

Study Officials

• Executive Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: October 5, 2016
• First Posted: October 7, 2016
• Study Start: January 10, 2017
• Primary Completion: May 25, 2021
• Study Completion: February 19, 2024
• Last Updated: November 26, 2024
• Results First Posted: June 27, 2022

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: 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.
• Access Criteria: 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.

Locations

DE (2); ES (1); TW (3); RO (1); SE (2); US (6); CZ (1); DK (1); PT (2); IL (1); KR (8); CA (2); GB (8); IT (6); PL (3); FR (7); JP (12); BR (1); GR (4); HU (1)