A Phase 1 Open-label, Dose-escalation Study Investigating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ASP2215 in Japanese Patients With Relapsed or Refractory Acute Myeloid Leukemia
Overview
- Phase
- Phase 1
- Intervention
- Gilteritinib
- Conditions
- Acute Myeloid Leukemia (AML)
- Sponsor
- Astellas Pharma Inc
- Enrollment
- 24
- Locations
- 5
- Primary Endpoint
- Safety and Tolerability assessed through adverse events to determine maximum tolerated dose
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The objectives of this study are to determine the safety and tolerability of ASP2215 as well as the maximum tolerated dose (MTD) based on the onset of dose limiting toxicity (DLT) and/or determine the recommended dose (RD) of ASP2215 for the next phase in subjects with relapsed or treatment-refractory acute myeloid leukemia (AML).
Detailed Description
This study will be conducted to determine the safety, tolerability, PK, PD, and efficacy of single and repeated oral dosing of ASP2215 once daily in patients with relapsed or refractory AML. After the determination of the MTD and/or RD, an expansion cohort might be set to further investigate the safety and efficacy of ASP2215. This study will consist of a single-dose period (Cycle 0, 2 days) and a repeated-dose period (Cycle 1 and subsequent cycles, each cycle consisting of 28 days). The enrolled subjects will orally receive their assigned single dose in Cycle 0 (Day -2), followed by a 2-day observation period (dosing day inclusive). In Cycle 1 and subsequent cycles (one cycle is defined as 28 days), the subjects will receive oral ASP2215 once daily repeatedly until one of the discontinuation criteria is met. Another dosing regimen may be considered such as dosing twice daily based on the safety and PK data that will become available. In this study, the Bayesian-Continual Reassessment Method (hereinafter, Bayesian-CRM) will be used as a reference for dose-escalation procedures, and based on the onset of DLTs, the RD level of the subsequent cohort will be set higher or lower. DLTs will be assessed during Cycle 0 and Cycle 1 (30 days). ASP2215 may be escalated by one dose level if the subject meets the criteria at the end of each cycle after Cycle 1 and the investigator/sub-investigator judges escalation of ASP2215 is of clinical benefit. Dose reduction of ASP2215 will be considered if study drug-related toxicities are observed in a subject.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject is defined as morphologically documented primary or secondary acute myeloid leukemia (AML) according to the World Health Organization (WHO) criteria (2008) and fulfills one of the following:
- •Refractory to prior induction chemotherapy
- •Relapsed after achieving remission with prior therapy
- •Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
- •Subject's interval from prior treatment to the time of study drug administration is at least 14 days for antineoplastic agents other than ASP2215 (except for hydroxyurea, which is given to control blast cells).
- •Subject's interval from prior treatment to the time of study drug (ASP2215) administration is at least 5 half-lives (if the half-life is unknown, 14 days) for other investigational products or drugs used for immunosuppressive therapy posthematopoietic stem cell transplantation (HSCT).
Exclusion Criteria
- •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 persistent non-hematological toxicities of ≥ Grade 2 (CTCAE v4), with symptoms and objective findings, due to prior AML treatment (including chemotherapy, kinase inhibitors, immunotherapy, investigational products, radiation therapy, and surgery)
- •Subject has received hematopoietic stem cell transplant (HSCT) and falls under either of the following:
- •Is within 2 months of transplant
- •Has persistent and clinically significant graft-versus-host disease requiring treatment
- •Has persistent non-hematological toxicities of ≥ Grade 2 related to the transplant
- •Subject has clinically active central nervous system leukemia
- •Subject has disseminated intravascular coagulation (DIC)
Arms & Interventions
Dose Escalation Cohort
ASP2215
Intervention: Gilteritinib
Outcomes
Primary Outcomes
Safety and Tolerability assessed through adverse events to determine maximum tolerated dose
Time Frame: Up to 17 months
Secondary Outcomes
- Pharmacokinetics of ASP2215: tmax(Cycle 0 Day -2 through Cycle 1 Day 1 and Cycle 1 Day 28)
- Pharmacokinetics of ASP2215 in plasma: Rac(AUC)(Cycle 1 Day 28)
- Pharmacokinetics of ASP2215 in urine: Ae48(Cycle 0 Day -2 through Cycle 1 Day 1)
- Pharmacokinetics of ASP2215 in plasma: Cmax(Cycle 0 Day -2 through Cycle 1 Day 1 and Cycle 1 Day 28)
- Pharmacokinetics of ASP2215 in plasma: C24(Cycle 0 Day -2 through Cycle 1 Day 1 and Cycle 1 Day 28)
- Pharmacokinetics of ASP2215 in plasma: t1/2(Cycle 0 Day -2 through Cycle 1 Day 1)
- Pharmacokinetics of ASP2215 in plasma: Rac(Cmax)(Cycle 1 Day 28)
- Pharmacokinetics of ASP2215 in plasma: Rac derived t1/2(Cycle 1 Day 28)
- Pharmacokinetics of ASP2215 in urine: Ae24(Cycle 0 Day -2 through Cycle 1 Day 1)
- Pharmacokinetics of ASP2215 in urine: Ae48%(Cycle 0 Day -2 through Cycle 1 Day 1)
- Pharmacokinetics of ASP2215 in urine: Aetau(Cycle 1 Day 28)
- Pharmacokinetics of ASP2215 in urine: Ae24%(Cycle 0 Day -2 through Cycle 1 Day 1)
- Response Rate(Up to 16 months)
- Pharmacokinetics of ASP2215 in plasma: AUCinf(Cycle 0 Day -2 through Cycle 1 Day 1)
- Pharmacokinetics of ASP2215 in plasma: AUC24(Cycle 0 Day -2 through Cycle 1 Day 1)
- Pharmacokinetics of ASP2215 in plasma: AUC48(Cycle 0 Day -2 through Cycle 1 Day 1)
- Pharmacokinetics of ASP2215 in plasma: Lambda z(Cycle 0 Day -2 through Cycle 1 Day 1)
- Pharmacokinetics of ASP2215 in plasma: Vz/F(Cycle 0 Day -2 through Cycle 1 Day 1)
- Pharmacokinetics of ASP2215 in plasma: AUCtau(Cycle 1 Day 28)
- Pharmacokinetics of ASP2215 in plasma: PTR(Cycle 1 Day 28)
- Pharmacokinetics of ASP2215 in plasma: Ctrough(Cycle 1 Day 8, Day 15, Day 22, Day 28 and Day 29)
- Pharmacokinetics of ASP2215 in urine: CLR(Cycle 0 Day -2 through Cycle 1 Day 1 and Cycle 1 Day 28)
- Pharmacokinetics of ASP2215 in urine: Aetau %(Cycle 1 Day 28)
- Pharmacokinetics of ASP2215 in plasma: CLF(Cycle 0 Day -2 through Cycle 1 Day 1 and Cycle 1 Day 28)
- Pharmacokinetics of ASP2215 in plasma: AUClast(Cycle 0 Day -2 through Cycle 1 Day 1)