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TerminatedNCT04240002Updated Jan 5, 2026Results posted

A 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)

A Phase 1/2 interventional study of gilteritinib and fludarabine in Acute Myeloid Leukemia (AML) and Acute Myeloid Leukemia With FMS-like Tyrosine Kinase 3 (FLT3) Mutation / Internal Tandem Duplication (ITD), sponsored by Astellas Pharma Global Development, Inc.. Terminated at 7 sites in 5 countries. Open to participants aged 6 Months to 21 Years. Per ClinicalTrials.gov, last updated 2026-01-05.

Sponsored by Astellas Pharma Global Development, Inc. · Phase 1/2, Interventional, and Treatment

Why this study was terminated
The study was terminated due to enrollment challenges.
Phase
Phase 1/2
Study type
Interventional
Enrollment
9
Allocation
Not applicable
Ages
6 Months to 21 Years
Sex
All
01

Study summary

The purpose of the phase 1 portion (dose escalation) of the study was 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) was to determine complete remission (CR) rates and composite complete remission (CRc) rates after two cycles of therapy. The study also assessed safety, tolerability and toxicities of gilteritinib in combination with FLAG, evaluated FLT3 inhibition, assessed pharmacokinetics (PK), performed serial measurements of minimal residual disease, obtained preliminary estimates of 1-year event free survival (EFS) and overall survival (OS) rate and assessed the acceptability as well as palatability of the formulation.

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

02

Conditions studied

  • Acute Myeloid Leukemia (AML)
  • Acute Myeloid Leukemia With FMS-like Tyrosine Kinase 3 (FLT3) Mutation / Internal Tandem Duplication (ITD)

Keywords

  • ASP2215
  • Acute Myeloid Leukemia
  • FLT3
  • AML
  • gilteritinib
03

In context

Leukemia, Myeloid, Acute

2,970 studies on the registry are indexed under Leukemia, Myeloid, Acute; 744 are open to participants now.

This study's enrollment of 9 is below the median of 41 across 2,508 interventional studies indexed under Leukemia, Myeloid, Acute.

Browse Leukemia, Myeloid, Acute studies →

Lead sponsor

Astellas Pharma Global Development, Inc. is the lead sponsor of 204 studies on the registry; 25 are open to participants now.

Of its 80 completed or terminated interventional studies of FDA-regulated products, 38 (48%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
6 Months to 21 Years
Sexes eligible
All
Accepts healthy volunteers
No

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 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).

    • 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).
    • 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).

  • Subject has fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

    • 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.

      • 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).

        • hydroxyurea,
        • low dose cytarabine (100 mg/m\^2 per dose once daily for 5 days) or
        • other low dose/maintenance therapies as per local site practice.
      • Subject who has received other FLT3 inhibitors (e.g., lestaurtinib, 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.
    • 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.

    • X-ray treatment (XRT):

      • 14 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.
  • For subject undergoing hematopoietic stem cell transplant (HSCT), at least 90 days must have elapsed since HSCT and subject must not have active graft-versus-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.

  • Subject must meet the following criteria as indicated on the clinical laboratory tests.

    • Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x upper limit normal (ULN) for age
    • Total serum bilirubin ≤ 1.5 x ULN for age
    • Estimated glomerular filtration rate of > 60 mL/min/1.73 m\^2.

  • A female subject is eligible to participate if she is not pregnant and at least 1 of the following conditions applies:

    • 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.
  • 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.
  • Female subject must not donate ova starting at Screening and throughout the study, and for 180 days after the final study drug administration.
  • 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.
  • 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.
  • Subject and subject's parent(s) or legal guardian agrees not to participate in another interventional study while on treatment.
  • 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)
  • 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.
  • Phase 2: Subject is positive for the FLT3 (ITD) mutation in bone marrow or blood as determined by the local institution.

Exclusion criteria

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
    • Prolonged Fridericia's Correction Formula (QTcF) interval on pre-entry electrocardiogram (ECG) (≥ 450 ms)
    • 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 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 is receiving or plans to receive concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
  • 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 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.

    • 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 must wait for at least 5 half-lives after stopping therapy with any investigational agent and before starting gilteritinib.
  • Subject has a known or suspected hypersensitivity to gilteritinib, cytarabine, fludarabine, granulocyte colony-stimulating factor (G-CSF) or any components of the formulation used.
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
9 participants (actual)

Study arms

  • Experimental
    Gilteritinib 2 mg/kg/day (Escalation Phase)

    Participants aged 2 years to less than 21 years with relapsed/refractory (R/R) FLT3 ITD and/or TKD Acute Myeloid Leukemia (AML) received 2 cycles (Cycle \[C\] 1 and C2) induction therapy with gilteritinib in combination with FLAG \[fludarabine, cytarabine and granulocyte colony-stimulating factor (G-CSF)\] chemotherapy. Gilteritinib tablet was administered at a starting dose of 2 milligrams/kilogram/day (mg/kg/day) (maximum 120 mg/day) orally once daily (QD) from days 8 to 21. FLAG regimen consisted of fludarabine: 30 milligrams per square meter (mg/m\^2) per day intravenously (IV) from day 1 to day 5; cytarabine: 2000 mg/m\^2 per day IV from day 1 to day 5; G-CSF (filgrastim): 5 micrograms per kilogram (μg/kg) per day subcutaneously (SC) or IV from day -1 to day 5. Each cycle = 28 days.

    Drug: gilteritinib · Drug: fludarabine · Drug: cytarabine · Drug: granulocyte colony-stimulating factor (G-CSF)

Interventions

  • Druggilteritinib

    Administered orally.

    Also known as: ASP2215

  • Drugfludarabine

    Administered by intravenous (IV) infusion

  • Drugcytarabine

    Administered by intravenous (IV) infusion

  • Druggranulocyte colony-stimulating factor (G-CSF)

    Administered by subcutaneous injection

06

What researchers measure

Primary outcomes

  1. Phase 1: Maximum Tolerated Dose (MTD) of Gilteritinib

    MTD reflects the highest dose that did not cause a Dose Limiting Toxicity (DLT).DLT:any Grade ≥3 non-hematologic/extramedullary toxicity with the following exceptions that occurred during the DLT observations like alopecia, anorexia, or fatigue, grade 3 vomiting or diarrhea that resolved(with or without supportive care) to ≤ grade 2 within 48 hours, grade 3 nausea that resolved(with or without supportive care) to ≤ grade 2 within 7 days, grade 3 elevation in total bilirubin (TBL) that is asymptomatic and that returned to ≤ grade 2 elevation within 7 days, grade 3 elevation in hepatic transaminases\[alanine aminotransferase (ALT/SGPT) aspartate aminotransferase (AST/SGOT) and gammaglutamyl transferase (GGT)\] or Alkaline Phosphatase (ALP) level that returns to ≤ grade 2 elevation within 14 days, grade 3 fever with neutropenia, with/without infection, grade 3 infection/grade 4 infections expected as direct complication of cytopenia due to active underlying leukemia, grade 3 mucositis.

    Time frame: C1D1 up to day 28

  2. Phase 1: Recommended Phase 2 Dose (RP2D) of Gilteritinib

    The RP2D was a safe dose of gilteritinib that demonstrated sufficient activity.

    Time frame: C1D1 up to day 28

  3. Phase 2: Complete Remission (CR) Rate

    CR rate was defined as the number of participants with best response of CR divided by the number of participants in the analysis population. CR was defined as a morphologically leukemia-free state post-baseline and had absolute neutrophil count (ANC) \>= 1 x 10\^9/L, platelet count \>= 100 x 10\^9/L and normal marrow differential with \< 5% blasts. and were red blood cell (RBC) and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion). There should be no evidence of extramedullary leukemia and no evidence of Auer rods. The blast counts in peripheral blood must be \<= 2%. Derived and investigator-assessed responses are reported.

    Time frame: From date of randomization to end of induction (induction= 1-2 cycles, each cycle = 28 days)

  4. Phase 2: Composite CR (CRc) Rate

    CRc was defined as participants who achieved either CR, complete remission with incomplete platelet recovery (CRp) or complete remission with incomplete hematologic recovery (CRi) at the visit. CR was defined as a morphologically leukemia-free state post-baseline and had ANC \>= 1 x 10\^9/L, platelet count \>= 100 x 10\^9/L and normal marrow differential with \< 5% blasts. and were RBC and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion). There should be no evidence of extramedullary leukemia and no evidence of Auer rods. The blast counts in peripheral blood must be \<= 2%. CRp was defined as met all CR criteria except incomplete platelet recovery (\< 100x10\^9/L). CRi was defined as met all CR criteria, except for incomplete hematological recovery with residual neutropenia \< 1x10\^9/L with or without complete platelet recovery. Derived and investigator-assessed responses are reported.

    Time frame: From date of randomization to end of induction (induction= 1-2 cycles, each cycle = 28 days)

  5. Duration of CR

    Duration of CR was defined as the time from the date of first CR until the date of documented relapse for participants who achieved CR. CR was defined as a morphologically leukemia-free state post-baseline and had ANC \>= 1 x 10\^9/L, platelet count \>= 100 x 10\^9/L and normal marrow differential with \< 5% blasts, and were RBC and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion). There should be no evidence of extramedullary leukemia and no evidence of Auer rods. The blast counts in peripheral blood must be \<= 2%. Relapse was defined as a reappearance of leukemic blasts in the peripheral blood or \>= 5% blasts in the bone marrow aspirate (BMA) not attributable to any other cause or reappearance or new appearance of extramedullary leukemia. Duration of CR was estimated using the Kaplan-Meier method.

    Time frame: From the date of first CR until the date of documented relapse for participants who achieved CR (Maximum duration: 28 months)

  6. Phase 1: Number of Participants With Dose Limiting Toxicity (DLT) of Gilteritinib

    DLT: any Grade \>=3 non-hematologic/extramedullary toxicity with the following exceptions that occurred during the DLT observation: Alopecia, anorexia, or fatigue. Grade 3 vomiting or diarrhea that resolved(with or without supportive care) to \<= grade 2 within 48 hours. Grade 3 nausea that resolved(with or without supportive care) to \<= grade 2 within 7 days. Grade 3 elevation in TBL that was asymptomatic and that returned to \<= grade 2 elevation within 7 days. Grade 3 elevation in hepatic transaminases (ALT/SGPT, AST/SGOT) and GGT) or ALP level that returns to \<= grade 2 elevation within 14 days. Grade 3 fever with neutropenia, with or without infection. Grade 3 infection or grade 4 infections expected as direct complication of cytopenia due to active underlying leukemia. Grade 3 mucositis.

    Time frame: C1D1 up to day 28

Secondary outcomes

  1. Percent Change of Phosphorylated FMS-like Tyrosine Kinase 3 (FLT3)

    Plasma inhibitory assay (PIA) of phosphorylated FLT3 was conducted by comparing baseline and post-treatment samples. Inhibition was summarized at each time point. PIA assay assesses the target inhibition in plasma. Plasma was incubated with a cell line expressing the drug target, and inhibition was reported as percent change from baseline (normalized to 100%).

    Time frame: Baseline, predose on C1D15, C1D21, C2D8, C2D15, C2D21 and 4 to 6 hours post-dose on C1D21

  2. Gilteritinib Plasma Concentration

    Plasma samples were used for pharmacokinetic assessments.

    Time frame: Predose on C1D8, C1D15, C1D21, C2D15, and 4 to 6 hours post-dose on C1D21

  3. Pharmacokinetics (PK) of Gilteritinib: Oral Clearance (CL/F)

    Time frame: Predose on C1D8, C1D15, C1D21, C2D15, and 4 and 6 hours post-dose on C1D21

  4. PK of Gilteritinib: Apparent Volume of Distribution (Vd/F)

    Time frame: Predose on C1D8, C1D15, C1D21, C2D15, and 4 and 6 hours post-dose on C1D21

  5. PK of Gilteritinib: Maximum Plasma Concentration (Cmax)

    Time frame: Predose on C1D8, C1D15, C1D21, C2D15, and 4 and 6 hours post-dose on C1D21

  6. PK of Gilteritinib: Time to Observed Cmax (Tmax)

    Time frame: Predose on C1D8, C1D15, C1D21, C2D15, and 4 and 6 hours post-dose on C1D21

  7. PK of Gilteritinib: Area Under the Concentration (AUC)

    Time frame: Predose on C1D8, C1D15, C1D21, C2D15, and 4 and 6 hours post-dose on C1D21

  8. 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 was defined as an adverse event observed after starting administration of the study drug until 28 days from the last study treatment.

    Time frame: From first dose up to 28 days after last dose (maximum duration approximately 55 months)

  9. Event Free Survival (EFS)

    EFS was defined as the time from first study drug dose to documented relapse or death, whichever occurred first. If none of these events occurred, EFS was censored at the last relapse-free assessment. Relapse was defined as a reappearance of leukemic blasts in the peripheral blood or \>= 5% blasts in the BMA not attributable to any other cause or reappearance or new appearance of extramedullary leukemia. EFS was estimated using the Kaplan-Meier method.

    Time frame: From first dose to documented relapse or death, whichever occurred first (maximum duration: 55 month)

  10. Overall Survival (OS)

    OS was defined as the time from the date of enrollment until the date of death from any cause (death date - enrollment date + 1). For a participant who was not known to have died by the end of study follow-up, OS was censored at the date of last contact (date of last contact - enrollment date + 1). OS was estimated using the Kaplan-Meier method.

    Time frame: From the date of enrollment until the date of death from any cause (maximum duration: 55 months)

  11. Number of Participants With Negative Minimal Residual Disease (MRD) Status

    MRD negative was defined as summed FLT3-ITD signal ratio of any post-baseline sample ≤10\^(-4).

    Time frame: From baseline up to approximately 55 months

  12. Percentage of Participants With MRD Negative Status in Relation to CR Rate

    MRD negative was defined as summed FLT3-ITD signal ratio of any post-baseline sample \<=10\^(-4). CR rate was defined as the number of participants with best response of CR divided by the number of participants in the analysis population. CR was defined as a morphologically leukemia-free state post-baseline and had ANC \>= 1 x 10\^9/L, platelet count \>= 100 x 10\^9/L and normal marrow differential with \< 5% blasts. and were RBC and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion). There should be no evidence of extramedullary leukemia and no evidence of Auer rods. The blast counts in peripheral blood must be \<= 2%. Derived and investigator-assessed responses are reported.

    Time frame: From baseline up to approximately 55 months

  13. Percentage of Participants With MRD Negative Status in Relation to CRc Rate

    MRD negative: summed FLT3-ITD signal ratio of any post-baseline sample \<=10\^(-4). CRc: participants who achieved either CR, complete remission with CRp or CRi at the visit. CR: morphologically leukemia-free state post-baseline and had ANC \>= 1 x 10\^9/L, platelet count \>= 100 x 10\^9/L and normal marrow differential with \< 5% blasts. and were RBC and platelet transfusion independent. There should be no evidence of extramedullary leukemia and no evidence of Auer rods. The blast counts in peripheral blood must be \<= 2%. CRp: all CR criteria except incomplete platelet recovery (\< 100x10\^9/L). CRi: met all CR criteria, except for incomplete hematological recovery with residual neutropenia \< 1x10\^9/L with or without complete platelet recovery. CRc rate: as number of participants with best response of CR divided by the number of participants in the analysis population. Derived and investigator-assessed responses are reported.

    Time frame: From baseline up to approximately 55 months

  14. Number of Participants With MRD Negative Status in Relation to OS

    MRD negative: summed FLT3-ITD signal ratio of any post-baseline sample ≤10\^(-4). OS was defined as the time from the date of enrollment until the date of death from any cause (death date - enrollment date + 1). For a participant who was not known to have died by the end of study follow-up, OS was censored at the date of last contact (date of last contact - enrollment date + 1).

    Time frame: From baseline up to approximately 55 months

  15. Number of Participants With Gilteritinib Acceptability and Palatability for Tablet

    Participants evaluated the taste of the study drug/tablets and indicated whether they would be willing (feeling) to take the study drug/tablets again by selecting one of the following categories: 'Like a lot,' 'Like a little,' 'Neither like nor dislike,' 'Dislike a little,' or 'Dislike a lot.'

    Time frame: C1D1, C1D8

07

Results

Posted Jan 5, 2026
Limitations and caveats
The study was terminated because of enrollment challenges due to the rarity of R/R AML in children and not related to any safety or efficacy issues.

Participant flow

Participants positive for FMS-like tyrosine kinase 3 (FLT3) \[internal tandem duplication (ITD) and/or tyrosine kinase domain (TKD)\] mutation in bone marrow or blood and positive for the FLT3 (ITD) mutation in bone marrow or blood were enrolled for phase 1 and phase 2 respectively.

Participant flow — Overall Study
MilestoneGilteritinib 2 mg/kg/Day (Escalation Phase)
Started9
Completed9
Not completed0

Outcome measures

PrimaryPhase 1: Maximum Tolerated Dose (MTD) of Gilteritinib

MTD reflects the highest dose that did not cause a Dose Limiting Toxicity (DLT).DLT:any Grade ≥3 non-hematologic/extramedullary toxicity with the following exceptions that occurred during the DLT observations like alopecia, anorexia, or fatigue, grade 3 vomiting or diarrhea that resolved(with or without supportive care) to ≤ grade 2 within 48 hours, grade 3 nausea that resolved(with or without supportive care) to ≤ grade 2 within 7 days, grade 3 elevation in total bilirubin (TBL) that is asymptomatic and that returned to ≤ grade 2 elevation within 7 days, grade 3 elevation in hepatic transaminases\[alanine aminotransferase (ALT/SGPT) aspartate aminotransferase (AST/SGOT) and gammaglutamyl transferase (GGT)\] or Alkaline Phosphatase (ALP) level that returns to ≤ grade 2 elevation within 14 days, grade 3 fever with neutropenia, with/without infection, grade 3 infection/grade 4 infections expected as direct complication of cytopenia due to active underlying leukemia, grade 3 mucositis.

Time frame:
C1D1 up to day 28
Reported as:
Number · mg/kg/day
Phase 1: Maximum Tolerated Dose (MTD) of Gilteritinib
mg/kg/dayGilteritinib 2 mg/kg/Day (Escalation Phase)
Phase 1: Maximum Tolerated Dose (MTD) of Gilteritinib2
PrimaryPhase 1: Recommended Phase 2 Dose (RP2D) of Gilteritinib

The RP2D was a safe dose of gilteritinib that demonstrated sufficient activity.

Time frame:
C1D1 up to day 28
Reported as:
Number · mg/kg/day
Phase 1: Recommended Phase 2 Dose (RP2D) of Gilteritinib
mg/kg/dayGilteritinib 2 mg/kg/Day (Escalation Phase)
Phase 1: Recommended Phase 2 Dose (RP2D) of Gilteritinib2
PrimaryPhase 2: Complete Remission (CR) Rate

CR rate was defined as the number of participants with best response of CR divided by the number of participants in the analysis population. CR was defined as a morphologically leukemia-free state post-baseline and had absolute neutrophil count (ANC) \>= 1 x 10\^9/L, platelet count \>= 100 x 10\^9/L and normal marrow differential with \< 5% blasts. and were red blood cell (RBC) and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion). There should be no evidence of extramedullary leukemia and no evidence of Auer rods. The blast counts in peripheral blood must be \<= 2%. Derived and investigator-assessed responses are reported.

Time frame:
From date of randomization to end of induction (induction= 1-2 cycles, each cycle = 28 days)
Reported as:
Number · Percentage of Participants
Phase 2: Complete Remission (CR) Rate
Percentage of ParticipantsGilteritinib 2 mg/kg/Day (Escalation Phase)
Derived33.3 (7.5 to 70.1)
Investigator33.3 (7.5 to 70.1)
PrimaryPhase 2: Composite CR (CRc) Rate

CRc was defined as participants who achieved either CR, complete remission with incomplete platelet recovery (CRp) or complete remission with incomplete hematologic recovery (CRi) at the visit. CR was defined as a morphologically leukemia-free state post-baseline and had ANC \>= 1 x 10\^9/L, platelet count \>= 100 x 10\^9/L and normal marrow differential with \< 5% blasts. and were RBC and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion). There should be no evidence of extramedullary leukemia and no evidence of Auer rods. The blast counts in peripheral blood must be \<= 2%. CRp was defined as met all CR criteria except incomplete platelet recovery (\< 100x10\^9/L). CRi was defined as met all CR criteria, except for incomplete hematological recovery with residual neutropenia \< 1x10\^9/L with or without complete platelet recovery. Derived and investigator-assessed responses are reported.

Time frame:
From date of randomization to end of induction (induction= 1-2 cycles, each cycle = 28 days)
Reported as:
Number · Percentage of Participants
Phase 2: Composite CR (CRc) Rate
Percentage of ParticipantsGilteritinib 2 mg/kg/Day (Escalation Phase)
Derived66.7 (29.9 to 92.5)
Investigator55.6 (21.2 to 86.3)
PrimaryDuration of CR

Duration of CR was defined as the time from the date of first CR until the date of documented relapse for participants who achieved CR. CR was defined as a morphologically leukemia-free state post-baseline and had ANC \>= 1 x 10\^9/L, platelet count \>= 100 x 10\^9/L and normal marrow differential with \< 5% blasts, and were RBC and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion). There should be no evidence of extramedullary leukemia and no evidence of Auer rods. The blast counts in peripheral blood must be \<= 2%. Relapse was defined as a reappearance of leukemic blasts in the peripheral blood or \>= 5% blasts in the bone marrow aspirate (BMA) not attributable to any other cause or reappearance or new appearance of extramedullary leukemia. Duration of CR was estimated using the Kaplan-Meier method.

Time frame:
From the date of first CR until the date of documented relapse for participants who achieved CR (Maximum duration: 28 months)
Reported as:
Median · days
Duration of CR
daysGilteritinib 2 mg/kg/Day (Escalation Phase)
Duration of CRNA (55.00 to NA)
PrimaryPhase 1: Number of Participants With Dose Limiting Toxicity (DLT) of Gilteritinib

DLT: any Grade \>=3 non-hematologic/extramedullary toxicity with the following exceptions that occurred during the DLT observation: Alopecia, anorexia, or fatigue. Grade 3 vomiting or diarrhea that resolved(with or without supportive care) to \<= grade 2 within 48 hours. Grade 3 nausea that resolved(with or without supportive care) to \<= grade 2 within 7 days. Grade 3 elevation in TBL that was asymptomatic and that returned to \<= grade 2 elevation within 7 days. Grade 3 elevation in hepatic transaminases (ALT/SGPT, AST/SGOT) and GGT) or ALP level that returns to \<= grade 2 elevation within 14 days. Grade 3 fever with neutropenia, with or without infection. Grade 3 infection or grade 4 infections expected as direct complication of cytopenia due to active underlying leukemia. Grade 3 mucositis.

Time frame:
C1D1 up to day 28
Reported as:
Number · Participants
Phase 1: Number of Participants With Dose Limiting Toxicity (DLT) of Gilteritinib
ParticipantsGilteritinib 2 mg/kg/Day (Escalation Phase)
Phase 1: Number of Participants With Dose Limiting Toxicity (DLT) of Gilteritinib0
SecondaryPercent Change of Phosphorylated FMS-like Tyrosine Kinase 3 (FLT3)

Plasma inhibitory assay (PIA) of phosphorylated FLT3 was conducted by comparing baseline and post-treatment samples. Inhibition was summarized at each time point. PIA assay assesses the target inhibition in plasma. Plasma was incubated with a cell line expressing the drug target, and inhibition was reported as percent change from baseline (normalized to 100%).

Time frame:
Baseline, predose on C1D15, C1D21, C2D8, C2D15, C2D21 and 4 to 6 hours post-dose on C1D21
Reported as:
Mean · Percent Change of pFLT3
Percent Change of Phosphorylated FMS-like Tyrosine Kinase 3 (FLT3)
Percent Change of pFLT3Gilteritinib 2 mg/kg/Day (Escalation Phase)
Cycle 1 Day 15 Pre-Dose15.00 ± 14.41
Cycle 1 Day 21 Pre-Dose11.96 ± 11.85
Cycle 1 Day 21 4-6 Hours Post-Dose7.32 ± 9.14
Cycle 2 Day 8 Pre-Dose63.97 ± 25.40
Cycle 2 Day 15 Pre-Dose9.90 ± 2.95
Cycle 2 Day 21 Pre-Dose6.03 ± 8.72
SecondaryGilteritinib Plasma Concentration

Plasma samples were used for pharmacokinetic assessments.

Time frame:
Predose on C1D8, C1D15, C1D21, C2D15, and 4 to 6 hours post-dose on C1D21
Reported as:
Mean · nanogram (ng)/mL
Gilteritinib Plasma Concentration
nanogram (ng)/mLGilteritinib 2 mg/kg/Day (Escalation Phase)
Cycle 1 Day 8 Pre-Dose0 ± 0
Cycle 1 Day 15 Pre-Dose251.93 ± 202.55
Cycle 1 Day 21 Pre-Dose225.25 ± 135.18
Cycle 1 Day 21 4-6 Hours Post-Dose439.00 ± 209.62
Cycle 2 Day 15 Pre-Dose145.07 ± 67.09
SecondaryPharmacokinetics (PK) of Gilteritinib: Oral Clearance (CL/F)
Time frame:
Predose on C1D8, C1D15, C1D21, C2D15, and 4 and 6 hours post-dose on C1D21

Results for this outcome have not been posted.

SecondaryPK of Gilteritinib: Apparent Volume of Distribution (Vd/F)
Time frame:
Predose on C1D8, C1D15, C1D21, C2D15, and 4 and 6 hours post-dose on C1D21

Results for this outcome have not been posted.

SecondaryPK of Gilteritinib: Maximum Plasma Concentration (Cmax)
Time frame:
Predose on C1D8, C1D15, C1D21, C2D15, and 4 and 6 hours post-dose on C1D21

Results for this outcome have not been posted.

SecondaryPK of Gilteritinib: Time to Observed Cmax (Tmax)
Time frame:
Predose on C1D8, C1D15, C1D21, C2D15, and 4 and 6 hours post-dose on C1D21

Results for this outcome have not been posted.

SecondaryPK of Gilteritinib: Area Under the Concentration (AUC)
Time frame:
Predose on C1D8, C1D15, C1D21, C2D15, and 4 and 6 hours post-dose on C1D21

Results for this outcome have not been posted.

SecondaryNumber 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 was defined as an adverse event observed after starting administration of the study drug until 28 days from the last study treatment.

Time frame:
From first dose up to 28 days after last dose (maximum duration approximately 55 months)
Reported as:
Number · Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
ParticipantsGilteritinib 2 mg/kg/Day (Escalation Phase)
Number of Participants With Treatment Emergent Adverse Events (TEAEs)9
SecondaryEvent Free Survival (EFS)

EFS was defined as the time from first study drug dose to documented relapse or death, whichever occurred first. If none of these events occurred, EFS was censored at the last relapse-free assessment. Relapse was defined as a reappearance of leukemic blasts in the peripheral blood or \>= 5% blasts in the BMA not attributable to any other cause or reappearance or new appearance of extramedullary leukemia. EFS was estimated using the Kaplan-Meier method.

Time frame:
From first dose to documented relapse or death, whichever occurred first (maximum duration: 55 month)
Reported as:
Median · days
Event Free Survival (EFS)
daysGilteritinib 2 mg/kg/Day (Escalation Phase)
Event Free Survival (EFS)123.00 (1.00 to NA)
SecondaryOverall Survival (OS)

OS was defined as the time from the date of enrollment until the date of death from any cause (death date - enrollment date + 1). For a participant who was not known to have died by the end of study follow-up, OS was censored at the date of last contact (date of last contact - enrollment date + 1). OS was estimated using the Kaplan-Meier method.

Time frame:
From the date of enrollment until the date of death from any cause (maximum duration: 55 months)
Reported as:
Median · months
Overall Survival (OS)
monthsGilteritinib 2 mg/kg/Day (Escalation Phase)
Overall Survival (OS)NA (4.80 to NA)
SecondaryNumber of Participants With Negative Minimal Residual Disease (MRD) Status

MRD negative was defined as summed FLT3-ITD signal ratio of any post-baseline sample ≤10\^(-4).

Time frame:
From baseline up to approximately 55 months
Reported as:
Number · Participants
Number of Participants With Negative Minimal Residual Disease (MRD) Status
ParticipantsGilteritinib 2 mg/kg/Day (Escalation Phase)
Number of Participants With Negative Minimal Residual Disease (MRD) Status4
SecondaryPercentage of Participants With MRD Negative Status in Relation to CR Rate

MRD negative was defined as summed FLT3-ITD signal ratio of any post-baseline sample \<=10\^(-4). CR rate was defined as the number of participants with best response of CR divided by the number of participants in the analysis population. CR was defined as a morphologically leukemia-free state post-baseline and had ANC \>= 1 x 10\^9/L, platelet count \>= 100 x 10\^9/L and normal marrow differential with \< 5% blasts. and were RBC and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion). There should be no evidence of extramedullary leukemia and no evidence of Auer rods. The blast counts in peripheral blood must be \<= 2%. Derived and investigator-assessed responses are reported.

Time frame:
From baseline up to approximately 55 months
Reported as:
Number · percentage of participants
Percentage of Participants With MRD Negative Status in Relation to CR Rate
percentage of participantsGilteritinib 2 mg/kg/Day (Escalation Phase)
Derived75.0 (19.4 to 99.4)
Investigator75.0 (19.4 to 99.4)
SecondaryPercentage of Participants With MRD Negative Status in Relation to CRc Rate

MRD negative: summed FLT3-ITD signal ratio of any post-baseline sample \<=10\^(-4). CRc: participants who achieved either CR, complete remission with CRp or CRi at the visit. CR: morphologically leukemia-free state post-baseline and had ANC \>= 1 x 10\^9/L, platelet count \>= 100 x 10\^9/L and normal marrow differential with \< 5% blasts. and were RBC and platelet transfusion independent. There should be no evidence of extramedullary leukemia and no evidence of Auer rods. The blast counts in peripheral blood must be \<= 2%. CRp: all CR criteria except incomplete platelet recovery (\< 100x10\^9/L). CRi: met all CR criteria, except for incomplete hematological recovery with residual neutropenia \< 1x10\^9/L with or without complete platelet recovery. CRc rate: as number of participants with best response of CR divided by the number of participants in the analysis population. Derived and investigator-assessed responses are reported.

Time frame:
From baseline up to approximately 55 months
Reported as:
Number · percentage of participants
Percentage of Participants With MRD Negative Status in Relation to CRc Rate
percentage of participantsGilteritinib 2 mg/kg/Day (Escalation Phase)
Derived100.0 (39.8 to 100.0)
Investigator100.0 (39.8 to 100.0)
SecondaryNumber of Participants With MRD Negative Status in Relation to OS

MRD negative: summed FLT3-ITD signal ratio of any post-baseline sample ≤10\^(-4). OS was defined as the time from the date of enrollment until the date of death from any cause (death date - enrollment date + 1). For a participant who was not known to have died by the end of study follow-up, OS was censored at the date of last contact (date of last contact - enrollment date + 1).

Time frame:
From baseline up to approximately 55 months
Reported as:
Number · participants
Number of Participants With MRD Negative Status in Relation to OS
participantsGilteritinib 2 mg/kg/Day (Escalation Phase)
Number of Participants With MRD Negative Status in Relation to OS1
SecondaryNumber of Participants With Gilteritinib Acceptability and Palatability for Tablet

Participants evaluated the taste of the study drug/tablets and indicated whether they would be willing (feeling) to take the study drug/tablets again by selecting one of the following categories: 'Like a lot,' 'Like a little,' 'Neither like nor dislike,' 'Dislike a little,' or 'Dislike a lot.'

Time frame:
C1D1, C1D8
Reported as:
Number · Participants
Number of Participants With Gilteritinib Acceptability and Palatability for Tablet
ParticipantsGilteritinib 2 mg/kg/Day (Escalation Phase)
C1D8 Tastes: Like a lot1
C1D8 Tastes: Like a little2
C1D8 Tastes: Neither like or dislike3
C1D8 Tastes: Dislike a little0
C1D8 Tastes: Dislike a lot0
C1D8 Feeling: Like a lot3
C1D8 Feeling: Like a little1
C1D8 Feeling: Neither like or dislike2
C1D8 Feeling: Dislike a little0
C1D8 Feeling: Dislike a lot0
C1D21 Tastes: Like a lot1
C1D21 Tastes: Like a little1
C1D21 Tastes: Neither like or dislike5
C1D21 Tastes: Dislike a little0
C1D21 Tastes: Dislike a lot0
C1D21 Feeling: Like a lot3
C1D21 Feeling: Like a little1
C1D21 Feeling: Neither like or dislike3
C1D21 Feeling: Dislike a little0
C1D21 Feeling: Dislike a lot0

Adverse events

Collected over All Cause: From randomization up to end of study (maximum duration approximately 55 months) AE: From first dose up to 28 days after last dose (maximum duration approximately 55 months). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Gilteritinib 2 mg/kg/Day (Escalation Phase)4/9 (44.4%)7/9 (77.8%)9/9 (100%)
Most frequent serious events
Showing 10 of 22
Most frequent serious events
EventGilteritinib 2 mg/kg/Day (Escalation Phase)
Febrile neutropeniaBlood and lymphatic system disorders2/9
Graft versus host disease in liverImmune system disorders2/9
SepsisInfections and infestations2/9
PyrexiaGeneral disorders1/9
Graft versus host disease in eyeImmune system disorders1/9
Graft versus host disease oralImmune system disorders1/9
Bacterial sepsisInfections and infestations1/9
CellulitisInfections and infestations1/9
Device related bacteraemiaInfections and infestations1/9
Device related infectionInfections and infestations1/9
Most frequent other events
Showing 10 of 103
Most frequent other events
EventGilteritinib 2 mg/kg/Day (Escalation Phase)
PyrexiaGeneral disorders6/9
Alanine aminotransferase increasedInvestigations6/9
Aspartate aminotransferase increasedInvestigations6/9
AnaemiaBlood and lymphatic system disorders5/9
NauseaGastrointestinal disorders5/9
DiarrhoeaGastrointestinal disorders4/9
VomitingGastrointestinal disorders4/9
CoughRespiratory, thoracic and mediastinal disorders4/9
RashSkin and subcutaneous tissue disorders4/9
Febrile neutropeniaBlood and lymphatic system disorders3/9

Baseline characteristics

Full Analysis Set (FAS) included all enrolled participants who received at least one dose of treatment regimen.

Age, Continuous
Age, Continuous(Years)Gilteritinib 2 mg/kg/Day (Escalation Phase)
Mean11.9 ± 2.4
Sex: Female, Male
Sex: Female, Male(Participants)Gilteritinib 2 mg/kg/Day (Escalation Phase)
Female3
Male6
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Gilteritinib 2 mg/kg/Day (Escalation Phase)
Hispanic or Latino1
Not Hispanic or Latino8
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Gilteritinib 2 mg/kg/Day (Escalation Phase)
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White9
More than one race0
Unknown or Not Reported0
Percent Inhibition of Phosphorylated FMS-like Tyrosine Kinase 3 (FLT3)
Percent Inhibition of Phosphorylated FMS-like Tyrosine Kinase 3 (FLT3)(Percentage of pFLT3)Gilteritinib 2 mg/kg/Day (Escalation Phase)
Mean100.00 ± 0.00
08

Study locations

7 sites
  • St. Jude Children's Research Hospital
    Memphis, Tennessee 38105, United States
  • Site DE49004
    Essen, North Rhine-Westphalia 45147, Germany
  • SIte IT39001
    Roma, 165, Italy
  • Site ES34001
    Barcelona, 08950, Spain
  • Site GB44001
    Birmingham, B4 6NH, United Kingdom
  • Site GB44005
    Cardiff, CF14 4XW, United Kingdom
  • Site UK44007
    Sutton, United Kingdom
09

References and documents

Publications

  • Connor P, Ribeiro R, Catala A, Norton A, Schundeln MM, Hasabou N, Delgado D, Heinloth A, Hill J, Gill S, Bigirumurame T, Tasian SK, Locatelli F. Gilteritinib and chemotherapy in children with relapsed/refractory FLT3-ITD AML: results from the phase 1/2 SKIPPER trial. Blood Adv. 2026 Jul 14;10(13):4786-4793. doi: 10.1182/bloodadvances.2026020144. PubMed 42101908 ↗
  • Abematsu T, Nishikawa T, Shiba N, Iijima-Yamashita Y, Inaba Y, Takahashi Y, Nakagawa S, Kodama Y, Okamoto Y, Kawano Y. Pediatric acute myeloid leukemia co-expressing FLT3/ITD and NUP98/NSD1 treated with gilteritinib plus allogenic peripheral blood stem cell transplantation: A case report. Pediatr Blood Cancer. 2021 Nov;68(11):e29216. doi: 10.1002/pbc.29216. Epub 2021 Jul 10. No abstract available. PubMed 34245496 ↗

Study documents

  • Study protocol · Jul 22, 2022
  • Statistical analysis plan · Mar 7, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No — Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 5, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04240002
Lead sponsor
Astellas Pharma Global Development, Inc.
Responsible party
Sponsor
First posted
Jan 27, 2020
Start date
Sep 4, 2020
Primary completion
Mar 11, 2025
Completion
Mar 17, 2025
Results posted
Jan 5, 2026
Last update
Jan 5, 2026

Study contacts

Medical Director
study director · Astellas Pharma Global Development

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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