FMS-like Tyrosine Kinase 3 (FLT3)/Internal Tandem Duplication (ITD) Positive Relapsed or Refractory Acute Myeloid Leukemia (AML) MedDRA version: 21.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 100000004864
Conditions
Interventions
Product Name: Gilteritinib
Product Code: ASP12215
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: GILTERITINIB
CAS Number: 1254053-43-4
Current Sponsor code: ASP2215
Concentration unit: m
Sponsors
Astellas Pharma Global Development, Inc. (APGD)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved informed consent and privacy language as required per national regulations (e.g., Health Insurance Portability and Accountability Act Authorization for US sites) must be obtained from the subject or subject’s parent or legal guardian and if required child assent prior to any study-related procedures (including withdrawal of prohibited medication, if applicable). 2. Subject is positive for the FLT3/ITD mutation in bone marrow or blood as determined by the local institution. 3. Subject is aged = 6 months and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subject has active CNS leukemia. 2. Subject has uncontrolled or significant cardiovascular disease 3. 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. 5. Subject is receiving or plans to receive concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol. 6. Subject has active clinically significant GVHD or is on treatment with systemic corticosteroids and is receiving > 0.5 mg/kg of prednisone (or equivalent) daily dose for GVHD. 7. Subject has active malignant tumors other than AML. 8. 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. 9. Subject requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP)3A. 10. Subject must wait for at least 5 half-lives after stopping therapy with any investigational agent and before starting gilteritinib.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1 (Dose Escalation Phase): To determine the maximum tolerated dose (MTD) and/or optimally safe and biologically active recommended phase 2 dose (RP2D) of gilteritinib given in sequential combination with fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG) in children, adolescents and young adults with relapsed/refractory (R/R) FMS like tyrosine kinase 3 (FLT3)/internal tandem duplication (ITD) acute myeloid leukemia (AML). Phase 2 (Dose Expansion Phase): To determine complete remission (CR) rates and composite complete remission (CRc) rates after 2 cycles of gilteritinib in sequential combination with FLAG in children, adolescents and young adults in R/R FLT3/ITD AML. ;Secondary Objective: The secondary objectives are: ? To assess the safety, tolerability and toxicities of gilteritinib when given in sequential combination with FLAG in children, adolescents, and young adults with R/R FLT3/ITD AML. ? To evaluate FLT3 inhibition due to gilteritinib treatment ? To characterize gilteritinib (and active metabolites if warranted) pharmacokinetics. ? To perform serial measurements of minimal residual disease (MRD) and examine the relationship with study endpoints. ? To obtain preliminary estimates of 1-year event-free survival (EFS) and overall survival (OS) rate. ? To assess the acceptability and palatability of the formulation.;Primary end point(s): Phase 1: Determination of MTD and/or RP2D based on the DLT and biologic activity according to PIA. Phase 2: o CRc rates (overall best response) after 2 cycles of therapy. o CR rates after 2 cycles of therapy ;Timepoint(s) of evaluation of this end point: Phase 1: DLT observation period will be 28 days from the start of cycle 1 day 1; for the first cycle only. Phase 2: CRc and CR rates after 2 cycles of therapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: After 2 cycles of therapy;Secondary end point(s): -Inhibition of phosphorylated FLT3 (pFLT3) measured by PIA assay -Gilteritinib plasma concentration -Pharmacokinetic parameters (e.g., CL/F, Vd/F) of gilteritinib (and active metabolites if warranted) -Safety, tolerability and toxicity assessments of gilteritinib when given in combination with FLAG-DNX and FLAG -EFS rate -OS rate -MRD assessment -Acceptability and palatability assessment of the liquid formulation | — |
Countries
Canada, Germany, Italy, Japan, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Unit Reg. Affairs
Astellas Pharma Europe B.V.
Outcome results
None listed