A Study of ASP2215 in Combination With Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia.

NCT02310321 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 2215-CL-0104
• Study Type: interventional
• Target: 97
• Locations: 3 countries
• Sites: 55

Brief Summary

The purpose of phase 1 part in this study was to determine the maximum tolerated dose (MTD) and/or recommended expansion dose (RED) of ASP2215 concomitant with cytarabine/idarubicin as induction chemotherapy based on the status of the onset of dose-limiting toxicity (DLT) in newly diagnosed Acute Myeloid Leukemia (AML) subjects. Phase 1 part also evaluated safety and tolerability and characterized the pharmacokinetic (PK) parameters of ASP2215 concomitant with induction and consolidation chemotherapy as well as evaluated the PK parameters of cytarabine concomitant with ASP2215. The purpose of phase 2 part was to evaluate efficacy of ASP2215 in combination with induction therapy. Phase 2 cohort also evaluated safety and characterized the PK parameters of ASP2215 in combination with induction and consolidation therapy followed by maintenance therapy in newly diagnosed FLT3-mutated AML subjects.

Conditions

Acute Myeloid Leukemia; FLT3-mutated Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia; Cytarabine; Idarubicin; ASP2215

Outcome Measures

Primary Outcomes (5)

• Phase 1 Part: Maximum Tolerated Dose (MTD) of Gilteritinib

  The MTD was defined as the highest dose of gilteritinib at which the posterior mean of the DLT incidence during Cycle 1 of induction therapy was estimated to be closest to 33%.

  Day 1 up to the end of Induction period cycle 1 (up to 42 days)

• Phase 1 Part: Recommended Expansion Dose (RED) of Gilteritinib

  RED was the recommended dose used in Phase 2 of the study that was decided by the sponsor's responsible person by comprehensively assessing the data obtained from the study.

  Day 1 up to the end of Induction period cycle 1 (up to 42 days)

• Phase 1 Part: Number of Participants With Dose Limiting Toxicities (DLTs) of Gilteritinib

  DLTs were defined as: Any Grade ≥ 3 non-hematologic or extramedullary toxicity with the following exceptions: * Anorexia or fatigue * Grade 3 nausea and/or vomiting if participant did not require tube feeding or total parenteral nutrition, or diarrhea if the events did not require or prolong hospitalization that could be managed to grade ≤ 2 with standard antiemetic or antidiarrheal medications used at prescribed dose within 7 days of onset. * Grade 3 mucositis that resolved to Grade ≤ 2 within 7 days of onset, fever with neutropenia, with or without infection, infection * Grade 4 peripheral neutrophil count \< 500/cubic millimeters (mm\^3) * Platelet count \< 20,000/mm\^3 due to bone marrow hypoplasia * Grade ≥ 3 platelet count \< 50,000/mm\^3 accompanying bleeding * Grade 4 platelet count \< 25,000/mm\^3 requiring platelet transfusion DLT was assessed until cycle 1 of dose evaluation induction period and until cycle 1 of dose expansion consolidation period.

  Day 1 up to the end of Consolidation Cycle 1 (approximately up to 4 months)

• Phase 1 Part: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE could therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. TEAE included both serious and non-serious AEs. TEAE for Phase 1 was defined as an AE observed after the date of first dose until 30 days after the last dose.

  From the date of first dose up to 30 days after the last dose ( maximum duration up to approximately 4.1 years)

• Phase 2 Part: Complete Remission (CR) Rate: Induction Period

  Percentage of participants with CR was reported. CR was defined as a morphologically leukemia-free state at the post-baseline visit, having a neutrophil count of ≥ 1,000/mm3 and platelet count of ≥ 100,000/mm3, bone marrow blasts \< 5%. No evidence of Auer rods and no evidence of extramedullary leukemia. The blast counts in peripheral blood was ≤ 2%.

  From the date of first dose up to the start of Consolidation (approximately up to 4 months)

Secondary Outcomes (21)

• Phase 1 Part: Maximum Concentration (Cmax) of Gilteritinib Concomitant With Induction and Consolidation Chemotherapy

  Induction period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 4 Consolidation period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 1

• Phase 1 Part: Time to Attain Cmax (Tmax) of Gilteritinib Concomitant With Induction and Consolidation Chemotherapy

  Induction period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 4 Consolidation period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 1

• Phase 1 Part: Area Under Plasma Concentration-time Curve From Time 0 to 24 (AUC24) of Gilteritinib Concomitant With Induction and Consolidation Chemotherapy

  Induction period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 4 Consolidation period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 1

• Phase 1 Part: Area Under The Concentration-Time Curve From The Time Zero to The Last Measurable Concentration (AUClast) of Gilteritinib Concomitant With Induction and Consolidation Chemotherapy

  Induction period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 4 Consolidation period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 1

• Phase 1 Part: Plasma Trough Concentration (Ctrough) of Gilteritinib Concomitant With Induction and Consolidation Chemotherapy

  Induction period: Pre-dose on Cycle 1 Day 8, 11, and 17 Consolidation period: Pre-dose on Cycle 1 Day 6 and 15

Study Arms (3)

Phase 1: Dose Evaluation (DEv)

EXPERIMENTAL

Induction period: Participants received 120 milligrams (mg) gilteritinib (3 tablets of 40 mg) orally, once daily from day 4 to 17 combined with chemotherapy (idarubicin: 12 mg per square meters per day \[mg/m\^2/day\] on days 1 to 3, cytarabine: 100 mg/m\^2/day on days 1 to 7) via intravenous (IV) infusion; in cycles (C) 1 and 2 (1 cycle= 42 days). Consolidation period: Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once daily from day 1 to 14 combined with chemotherapy (cytarabine: 1500 mg/m\^2, twice daily on days 1, 3, and 5) via IV infusion; in the consolidation period in C1 to 3 (1 cycle= 28 days). Duration of infusion was determined by site clinical practice and local package insert in both induction and consolidation periods.. Maintenance period: Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once daily from days 1 to 28 in the maintenance period in C1 to 26 or untill discontinuation criterion is met (1 cycle= 28 days).

Drug: Gilteritinib; Drug: Idarubicin; Drug: Cytarabine

Phase 1: Dose Expansion (DEx)

EXPERIMENTAL

Induction period: Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day from days 4 to 17 in combination with chemotherapy (idarubicin: 12 mg/m\^2/day on days 1 to 3, cytarabine: 100 mg/m\^2/day on days 1 to 7) via IV infusion; in the induction period in C1 and 2 (1 cycle= 42 days). Consolidation period: Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day from days 1 to 14 in combination with chemotherapy (cytarabine: 1500 mg/m\^2, twice daily on days 1, 3, and 5) via IV infusion; in the consolidation period in C1 to 3 (1 cycle= 28 days). Duration of infusion was determined based on site clinical practice and the local package insert in both induction and consolidation periods. Maintenance period: Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day from days 1 to 28 in the maintenance period in C1 to 26 or a discontinuation criterion is met (1 cycle= 28 days).

Drug: Gilteritinib; Drug: Idarubicin; Drug: Cytarabine

Phase 2: FLT3-mutated AML

EXPERIMENTAL

Induction period: Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once daily from days 8 until blood recovery combined with chemotherapy (idarubicin: 12 mg/m\^2/day on days 1 to 3, cytarabine: 100 mg/m\^2/day on days 1 to 7) via IV infusion; in C1 and 2. Each cycle was extended until blood recovery was observed. Consolidation period: Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once daily from days 1 until blood recovery combined with chemotherapy (cytarabine: 1500 mg/m\^2, twice daily on days 1, 3, and 5) via IV infusion; in C1 to 3. Each cycle was extended until blood recovery was observed. Duration of infusion was based on site clinical practice and the local package insert in both induction and consolidation periods. Maintenance period: Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once daily from days 1 to 28 in the maintenance period in C1 to 26 or a discontinuation criterion is met (1 cycle= 28 days).

Drug: Gilteritinib; Drug: Idarubicin; Drug: Cytarabine

Interventions

Gilteritinib DRUG

Once-daily oral administration on 14 consecutive days in every cycle in each period.

Also known as: Xospata, ASP2215

Phase 1: Dose Evaluation (DEv); Phase 1: Dose Expansion (DEx); Phase 2: FLT3-mutated AML

Idarubicin DRUG

Induction period: Once-daily intravenous injection of 12 mg/m\^2 idarubicin on 3 consecutive days.

Phase 1: Dose Evaluation (DEv); Phase 1: Dose Expansion (DEx); Phase 2: FLT3-mutated AML

Cytarabine DRUG

Induction period: Once-daily intravenous injection of 100 mg/m\^2 cytarabine on 7 consecutive days. Consolidation period: Twice-daily intravenous injection of 1.5 g/m\^2 cytarabine on Days 1, 3, and 5.

Phase 1: Dose Evaluation (DEv); Phase 1: Dose Expansion (DEx); Phase 2: FLT3-mutated AML

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \[Phase 1 part\]
• Subject is defined as having previously untreated de novo AML according to the World Health Organization (WHO) criteria (2008) within 28 days prior to study enrollment.
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• Subject must meet all of the following criteria in the laboratory test at screening:
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels of ≤ 2.5 × institutional upper limit of normal (ULN)
• Total serum bilirubin level of ≤ 1.5 × institutional ULN
• Serum creatinine level of ≤ 1.5 × institutional ULN or an estimated glomerular filtration rate (eGFR) of \> 50 mL/min
• Subject is suitable for oral administration of ASP2215.
• Female subject falls under the following:
• Of non-childbearing potential:
• ・Post-menopausal (defined as at least 1 year with no menses without a medical reason such as drug administration) at screening, or
• ・Documented surgically sterile or status post-hysterectomy (at least 1 month prior to screening)
• Of childbearing potential:
• ・Has a negative result for the pregnancy test at screening, and
• ・Agrees to use an appropriate contraception starting at screening and throughout the study period and for 60 days after the final study drug administration

You may not qualify if:

• \[Phase 1 part\]
• Subject was diagnosed with acute promyelocytic leukemia (APL).
• Subject has breakpoint cluster region-abelson (BCR-ABL)-positive leukemia (chronic myelogenous leukemia in blast crisis).
• Subject has active malignant tumors other than AML or myelodysplastic syndrome (MDS).
• Subject has received prior AML treatment except for the following:
• Urgent leukapheresis
• Hydroxyurea administration for emergency treatment of hyperleukocytosis (≤ 7 days)
• Administration of retinoic acid before the diagnosis to exclude APL (≤ 7 days)
• Supportive care using growth factors or cytokines
• Steroid administration to treat hypersensitivity or blood transfusion reactions
• Subject has clinically active central nervous system leukemia.
• Subject has disseminated intravascular coagulation (DIC).
• Subject has had major surgery within 28 days prior to the first study drug administration.
• Subject has had radiation therapy within 28 days prior to the first study drug administration.
• Subject has congestive heart failure of New York Heart Association (NYHA) class 3 or 4, or subject with a past history of congestive heart failure of NYHA class 3 or 4 and in whom echocardiogram (ECHO) or Multiple Gate Acquisition (MUGA) scan performed within 3 months prior to screening or at screening showed a left ventricular ejection fraction (LVEF) of \< 45%.

Sponsors & Collaborators

• Astellas Pharma Inc: lead

Study Sites (55)

Site JP81037

Anjo, Aichi-ken, Japan

Location

Site JP00003

Nagoya, Aichi-ken, Japan

Location

Site JP81003

Nagoya, Aichi-ken, Japan

Location

Site JP81027

Nagoya, Aichi-ken, Japan

Location

Site JP81038

Toyohashi, Aichi-ken, Japan

Location

Site JP81010

Narita, Chiba, Japan

Location

Site JP81039

Matsuyama, Ehime, Japan

Location

Site JP81007

Yoshida-gun, Fukui, Japan

Location

Site JP00002

Maebashi, Gunma, Japan

Location

Site JP81001

Maebashi, Gunma, Japan

Location

Site JP81026

Fukuyama, Hiroshima, Japan

Location

Site JP81018

Ōtake, Hiroshima, Japan

Location

Site JP81014

Sapporo, Hokkaido, Japan

Location

Site JP81015

Sapporo, Hokkaido, Japan

Location

Site JP81043

Himeji, Hyōgo, Japan

Location

Site JP00007

Kobe, Hyōgo, Japan

Location

Site JP81006

Kobe, Hyōgo, Japan

Location

Site JP81036

Mito, Ibaraki, Japan

Location

Site JP81023

Tsukuba, Ibaraki, Japan

Location

Site JP81020

Kanazawa, Ishikawa-ken, Japan

Location

Site JP81013

Isehara, Kanagawa, Japan

Location

Site JP00006

Yokohama, Kanagawa, Japan

Location

Site JP81005

Yokohama, Kanagawa, Japan

Location

Site JP81024

Yokohama, Kanagawa, Japan

Location

Site JP81035

Sendai, Miyagi, Japan

Location

SIte JP81011

Ōmura, Nagasaki, Japan

Location

Site JP81041

Tenri, Nara, Japan

Location

Site JP81022

Shimono, Tochigi, Japan

Location

Site JP81040

Bunkyo-ku, Tokyo, Japan

Location

Site JP00005

Shinagawa-ku, Tokyo, Japan

Location

Site JP81032

Shinagawa-ku, Tokyo, Japan

Location

Site JP81029

Akita, Japan

Location

Site JP81008

Chiba, Japan

Location

Site JP00001

Fukuoka, Japan

Location

Site JP81004

Fukuoka, Japan

Location

Site JP81025

Fukuoka, Japan

Location

Site JP81031

Fukushima, Japan

Location

Site JP81030

Gifu, Japan

Location

Site JP81033

Kochi, Japan

Location

Site JP81028

Kumamoto, Japan

Location

Site JP81016

Kyoto, Japan

Location

Site JP81012

Nagasaki, Japan

Location

Site JP81009

Okayama, Japan

Location

Site JP81019

Osaka, Japan

Location

Site JP81021

Osaka, Japan

Location

Site KR82005

Busan, South Korea

Location

Site KR82002

Incheon, South Korea

Location

Site KR82001

Seoul, South Korea

Location

Site KR82003

Seoul, South Korea

Location

Site KR82004

Seoul, South Korea

Location

Site KR82006

Seoul, South Korea

Location

Site TW88604

Kaohsiung City, Taiwan

Location

Site TW88602

Taichung, Taiwan

Location

Site TW88601

Tainan, Taiwan

Location

Site TW88603

Taoyuan District, Taiwan

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

gilteritinib; Idarubicin; Cytarabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Clinical Transparency
• Organization: Astellas Pharma Inc.

astellas.resultsdisclosure@astellas.com

800-888-7704

Study Officials

• Medical Director

  Astellas Pharma Inc

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2014
• First Posted: December 8, 2014
• Study Start: February 26, 2015
• Primary Completion: August 25, 2021
• Study Completion: July 9, 2024
• Last Updated: September 2, 2025
• Results First Posted: October 16, 2024

Record last verified: 2025-08

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

KR (6); TW (4); JP (45)