NCT05330377

GM-CLAG in Relapsed/Refractory FLT3-mutated AML

Phase Ib Trial of Gilteritinib in Combination With Mitoxantrone, Cladribine, Cytarabine and Filgrastim (GM-CLAG) for Relapsed/Refractory FLT3-mutated Acute Myeloid Leukemia

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Ayman H Qasrawi · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate the dose-limiting toxicities (DLT) and define the maximum tolerated dose (MTD) and the recommended phase II study dose of gilteritinib when combined with mitoxantrone, cladribine, cytarabine and filgrastim (GM-CLAG) in participants with FLT3- mutated relapsed or refractory (R/R) acute myeloid leukemia (AML).

Detailed description

The treatment of FLT3- mutated relapsed or refractory (R/R) is challenging. Gilteritinib, as a single agent, is the first FLT3 inhibitor to be FDA approved in the R/R setting. This phase I clinical trial will evaluate DLT/MTD and the recommended phase II study dose of gilteritinib when combined with mitoxantrone, cladribine, cytarabine and filgrastim (CLAG-M) in patients with FLT3- mutated R/R AML. This study will also evaluate the pharmacodynamics and pharmacokinetics of gilteritinib when combined with CLAG-M at specific time points. Although this combination has not been established to have superior clinical benefit in comparison to single-agent gilteritinib, the objective of this trial is to provide a possible therapeutic benefit in addition to safety and tolerability.

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Gilteritinib 40 MG Oral Tablet	Gilteritinib is an oral FLT3 inhibitor, and is active against both FLT3-ITD and FLT3-TKD mutations. Gilteritinib will be given orally according to the assigned phase I dose cohort starting day 6 until day 19. Participants will be given the daily dose with water as at the same time each morning. Gilteritinib should be taken at least 2 hours after or 1 hour before consuming food.
DRUG	Cladribine	Cladribine is given intravenously at a dose of 5 mg/m2 I.V. over 2 hours once per day on days 1 to 5.
DRUG	Cytarabine	Cytarabine is given intravenously at a dose of 2,000 mg/m2 I.V. over 4 hours once per day on days 1 to 5, given second, 2 hours after cladribine.
DRUG	Filgrastim	Filgrastim (GCSF) or biosimilar, will be given at a dose of 300 mcg S.C. once per day on days 0 to 5, started 24 hours prior to chemotherapy. If WBC is \> 20 × 109/L on day 0, the filgrastim dose on day 0 will be omitted.
DRUG	Mitoxantrone	Mitoxantrone is given intravenously at a dose of 10 mg/m2 I.V. over 2 hours once per day on days 1 to 3.

Timeline

• Start date: 2023-03-01
• Primary completion: 2027-05-30
• Completion: 2032-05-30
• First posted: 2022-04-15
• Last updated: 2023-04-25

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study