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)
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).
Timeline
- Start
- 2020-09-04
- Primary completion
- 2025-03-11
- Completion
- 2025-03-17
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.
- 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.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Gilteritinib | Small molecule | 2 mg/kg | Oral |
| Background | Cytarabine | Small molecule | 2000 mg/m2 | Intravenous |
| Background | Fludarabine | Small molecule | 30 mg/m2 | Intravenous |
| Background | filgrastim | Protein / enzyme biologic | 5 ug/kg | Subcutaneous |