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)

Official Title

A Phase 1/2, Multicentre, 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)

Summary:

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 2 cycles in phase 1 or 2 will have the option to participate in long term treatment (LTT) with gilteritinib (for up to 2 years).

Trial Description

Primary Outcome:

  • Number of participants with dose limiting toxicity (DLT) (phase 1/dose escalation)
  • Complete Remission (CR) rate after 2 cycles of therapy (phase 2)
  • Composite complete remission (CRc) rate after 2 cycles of therapy (phase 2)
Secondary Outcome:
  • Number of participants with Adverse Events (AEs)
  • Number of participants with vital sign abnormalities and /or adverse events (AEs)
  • Number of participants with laboratory value abnormalities and/or adverse events (AEs)
  • Number of participants with electrocardiogram (ECG) abnormalities and/or adverse events (AEs)
  • Percentage of inhibition of phosphorylated FLT3 in participants.
  • Pharmacokinetics (PK) of gilteritinib: oral clearance (CL/F)
  • PK of gilteritinib: apparent volume of distribution (Vd/F)
  • PK of gilteritinib: Maximum Concentration (Cmax)
  • PK of gilteritinib: Time of Maximum Concentration (tmax)
  • PK of gilteritinib: Area Under the Concentration (AUC)
  • Duration of Event Free Survival (EFS)
  • Duration of Overall survival (OS)
  • The number of participants with negative minimal residual disease (MRD) status
  • Number of participants with MRD negative status in relation to CR rate
  • Number of participants with MRD negative status in relation to CRc rate
  • Number of participants with MRD negative status in relation to Overall survival (OS)
  • Clinical Outcome Assessment of Taste

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society