A Phase 1/2, Multicenter, Open-Label, Single Arm, Dose Escalation and Expansion Study of Gilteritinib (ASP2215) Combined With Chemotherapy in Children, Adolescents and Young Adults With FMS-like Tyrosine Kinase 3 (FLT3)/Internal Tandem Duplication (ITD) Positive Relapsed or Refractory Acute Myeloid Leukemia (AML)

  • End date
    Sep 30, 2026
  • participants needed
  • sponsor
    Astellas Pharma Global Development, Inc.
Updated on 22 October 2022
granulocyte colony stimulating factor
serum bilirubin level
refractory acute myeloid leukemia (aml)
blast cells
colony stimulating factor
hematopoietic growth factors


The purpose of the phase 1 portion (dose escalation) of the study will be to establish an optimally safe and biologically active recommended phase 2 dose (RP2D) and/or to determine maximum tolerated dose (MTD) for gilteritinib in sequential combination with fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG). The purpose of the phase 2 portion (dose expansion) is to determine complete remission (CR) rates and composite complete remission (CRc) rates after two cycles of therapy. The study will also assess safety, tolerability and toxicities of gilteritinib in combination with FLAG, evaluate FLT3 inhibition, assess pharmacokinetics (PK), perform serial measurements of minimal residual disease, obtain preliminary estimates of 1-year event free survival (EFS) and overall survival (OS) rate and assess the acceptability as well as palatability of the formulation.

One cycle is defined as 28 days of treatment. A participant completing 1 or 2 treatment cycles in phase 1 or 2 will have the option to participate in long term treatment (LTT) with gilteritinib (for up to 2 years).

Condition Acute Myeloid Leukemia (AML), Acute Myeloid Leukemia With FMS-like Tyrosine Kinase 3 (FLT3) Mutation / Internal Tandem Duplication (ITD)
Treatment cytarabine, Fludarabine, Gilteritinib, granulocyte colony-stimulating factor (G-CSF)
Clinical Study IdentifierNCT04240002
SponsorAstellas Pharma Global Development, Inc.
Last Modified on22 October 2022


Yes No Not Sure

Inclusion Criteria

Subject is aged ≥ 6 months and < 21 years of age at the time of signing informed consent and/or assent, as applicable
For phase 2: Enrollment of subjects from 6 months to less than 1 year and 1 year to less than 2 years will be dependent on the establishment of recommended phase 2 dose (RP2D) in the respective age groups during phase 1
Subject has a diagnosis of acute myeloid leukemia (AML) according to The
In the phase 1 portion of the study, subject must be in first or greater relapse or refractory to induction therapy with no more than 1 attempt at remission induction (up to 2 induction cycles)
French-American-British (FAB) classification with ≥ 5% blasts in the bone
marrow, with or without extramedullary disease (except subjects with active
central nervous system [CNS] leukemia)
Myelosuppressive chemotherapy
For subject who relapses while receiving cytotoxic therapy, at least 21 days must have elapsed since the completion of cytotoxic therapy and prior to screening, unless the subject has recovered earlier than 21 days
For the phase 2 portion of the study, subject must be in refractory to or at the first hematologic relapse after first-line remission induction AML therapy (up to 2 induction cycles)
Cytoreduction with the following can be initiated and continued for up to 24 hours prior to the start of systemic protocol therapy (cycle 1 day -1)
Subject has fully recovered from the acute toxic effects of all prior chemotherapy
immunotherapy, or radiotherapy prior to entering this study
low dose cytarabine (100 mg/m^2 per dose once daily for 5 days) or
Biologic (anti-neoplastic agent): at least 7 days must have elapsed since the completion of therapy with a biologic agent and prior to screening. For agents that have known adverse events (AEs) occurring beyond 7 days after administration, this period must be extended beyond the time during which AEs are known to occur
other low dose/maintenance therapies as per local site practice
X-ray treatment (XRT)
days must have elapsed for local palliative XRT for CNS chloromas and prior to screening; no washout period is necessary for other chloromas
Prior to screening, 90 days must have elapsed if the subject had a prior traumatic brain injury or has received craniospinal XRT
Subject who has received other FLT3 inhibitors (e.g., lestaurtinib
Subject must meet the following criteria as indicated on the clinical laboratory tests
sorafenib, etc) is eligible for this study
Hematopoietic growth factors: at least 7 days must have elapsed since the
completion of therapy with a growth factor and prior to screening
Not a woman of childbearing potential (WOCBP) OR
WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 180 days after the final study drug administration
For subject undergoing hematopoietic stem cell transplant (HSCT), at least 90 days
Female subject must not donate ova starting at Screening and throughout the study, and for 180 days after the final study drug administration
must have elapsed since HSCT and subject must not have active graft-versus-
A male subject with female partner(s) of childbearing potential must agree to use contraception during the treatment period and for at least 180 days after the final study drug administration
host disease (GVHD)
Subject has Karnofsky score ≥ 50 (if the subject is of ≥ 16 years of age) or Lansky score of ≥ 50 (if the subject is < 16 years of age). A score < 50 is acceptable if related to the subject's leukemia
A male subject must not donate sperm during the treatment period and for at least 120 days after the final study drug administration
Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 180 days after the final study drug administration
Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x upper limit normal (ULN) for age
Live Vaccines - At least 6 weeks must have elapsed since the administration of the last dose of a live vaccine and prior to the initiation of study treatment (cycle 1, day -1)
Total serum bilirubin ≤ 1.5 x ULN for age
Subject and subject's parent(s) or legal guardian agrees not to participate in another interventional study while on treatment
Estimated glomerular filtration rate of > 60 mL/min/1.73 m^2
Phase 2: Subject is positive for the FLT3 (ITD) mutation in bone marrow or blood as determined by the local institution
A female subject is eligible to participate if she is not pregnant and at least 1 of
the following conditions applies
Phase 1: Subject is positive for FLT3 (ITD and/or tyrosine kinase domain [TKD]) mutation in bone marrow or blood as determined by the local institution
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

Exclusion Criteria

Subject has active CNS leukemia
Subject has uncontrolled or significant cardiovascular disease, including
Diagnosed or suspected congenital long QT syndrome or any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes (TdP)); any history of arrhythmia will be discussed with the sponsor prior to subject's entry into the study
Any history of second or third degree heart block (may be eligible if the subject currently has a pacemaker)
Heart rate < 50 beats/minute on pre-entry ECG
Uncontrolled hypertension
Complete left bundle branch block
Subject is receiving or plans to receive concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol
Subject has active malignant tumors other than AML
Subject has any significant concurrent disease, illness, psychiatric disorder or social issue that would compromise subject safety or compliance; interfere with consent, study participation, follow-up or interpretation of study results
Subject has hypokalemia and/or hypomagnesemia at Screening (defined as values below institutional lower limit of normal [LLN]). Repletion of potassium and magnesium levels during the screening period is allowed
Subject requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP)3A/P-glycoprotein (P-gp)
Subject is known to have human immunodeficiency virus infection
Subject has active hepatitis B or C, or other active hepatic disorder
Prolonged Fridericia's Correction Formula (QTcF) interval on pre-entry electrocardiogram (ECG) (≥ 450 ms)
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 a known or suspected hypersensitivity to gilteritinib, cytarabine, fludarabine, granulocyte colony-stimulating factor (G-CSF) or any components of the formulation used
Subject has systemic fungal, bacterial, viral or other infection that is exhibiting
ongoing signs/symptoms related to the infection without improvement despite
appropriate antibiotics or other treatment. The subject needs to be off
pressors and have negative blood cultures for 48 hours
Subject has active clinically significant GVHD or is on treatment with immunosuppressive drugs for treatment of active GVHD, with the exception of subjects being weaned from systemic corticosteroids where the subject is receiving ≤ 0.5 mg/kg of prednisone (or equivalent) daily dose for prior GVHD. Subject has received calcineurin inhibitors within 4 weeks prior to screening, unless used as GVHD prophylaxis
Subject must wait for at least 5 half-lives after stopping therapy with any
investigational agent and before starting gilteritinib
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