NCT03135054

Combination of Quizartinib and Omacetaxine Mepesuccinate for AML Carrying FLT3-ITD

A Phase II Single-arm Open-labeled Study Evaluating Combination of Quizartinib and Omacetaxine Mepesuccinate (QUIZOM) in Newly Diagnosed or Relapsed/Refractory AML Carrying FLT3-ITD

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: The University of Hong Kong · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The study aims to test if combination of quizartinib (AC220) and omacetaxine mepesuccinate (OM, also known as homoharringtonine) results in durable composite complete remission (CRc) in patients with newly diagnosed or relapsed/refractory (R/R) acute myeloid leukemia (AML) carrying FLT3-ITD (Fms-Like Tyrosine Kinase 3 - Internal Tandem Duplication).

Detailed description

The type of AML being studied in this clinical trial is known as FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) positive AML. This type of AML has an alteration (or mutation) in genes, which may associated with high risk of relapse after conventional chemotherapy and hence an extremely poor clinical outcome. Second generation FLT3 inhibitors including quizartinib are effective in inducing remission. However, their effects are only transient. There is an unmet clinic need to enhance their effectiveness, hence clinical application. This is a Phase II single-arm open-labeled study. A total of 40 eligible patients with consent will be recruited, including 20 patients with newly diagnosed and 20 with R/R FLT3-ITD AML. For newly diagnosed patients, diagnostic bone marrow (BM) and/or peripheral blood (PB) will be evaluated by next generation sequencing (NGS) based on myeloid panel that comprises 54 myeloid genes as well as their in vitro response to QUIZOM based on an in-house platform that was established in our laboratory. FLT3-ITD allelic burden will also be evaluated. For R/R patients, FLT3-ITD status and allelic burden will be confirmed before QUIZOM treatment. Both groups of patients will receive quizartinib 30 mg daily continuously and OM 1.5 mg/m2 daily for 7 days every 28 days until progression or allogeneic hematopoietic stem cell transplantation (HSCT). BM examination will be performed on day 21 to document morphological response and FLT3-ITD allelic burden. At leukemia progression, BM and/or PB samples will be collected and their in vitro response to QUIZOM examined. The tyrosine kinase domain (TKD) of FLT3 will also be sequenced and FLT3-ITD allelic burden will be evaluated. Eligible patients will receive QUIZOM comprising quizartinib and OM. The starting dose of quizartinib will be 30 mg/day unless the patients are taking a strong CYP3A4 inhibitor in which case the dose will be 20 mg /day. Quizartinib should be taken continuously throughout the treatment period unless there is no evidence of response at first assessment on day 21 or progressive disease at any time during the treatment. OM will be given at 1.5 mg/m2/day (maximum dose 3 mg) for 7 days (concurrently with quizartinib) in 28-day cycle. QUIZOM will be continued until leukemia progression or allogeneic HSCT. Thereafter, patients will be followed up and information about disease status and survival will be collected.

Conditions

• AML
• FLT3-ITD Mutation

Interventions

Type	Name	Description
DRUG	Quizartinib	Quizartinib is an oral FLT3 receptor tyrosine kinase inhibitor
DRUG	Omacetaxine Mepesuccinate Injection	Omacetaxine Mepesuccinate is a pharmaceutical drug substance that is indicated for treatment of chronic myeloid leukemia (CML)

Timeline

• Start date: 2017-10-01
• Primary completion: 2020-10-01
• Completion: 2021-10-01
• First posted: 2017-05-01
• Last updated: 2020-12-10

Locations

1 site across 1 country: Hong Kong