NCT03170895

Combination of Sorafenib and Omacetaxine Mepesuccinate in Newly Diagnosed or Relapsed/Refractory AML Carrying FLT3-ITD

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 5 (actual)
• 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 sorafenib 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. FLT3 inhibitors including sorafenib 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 sorafenib and omacetaxine mepesuccinate (OM) 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 treatment. Both groups of patients will receive sorafenib 400 mg twice daily continuously and OM 1.5 mg/m2 daily for 7 days every 28 days until progression or allogeneic hematopoietic stem cell transplantation (HSCT). Thereafter, patients will be followed up and information about disease status and survival will be collected. BM examination will be performed on day 28 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 sorafenib and OM examined. The tyrosine kinase domain (TKD) of FLT3 will also be sequenced and FLT3-ITD allelic burden will be evaluated.

Conditions

• AML
• FLT3-ITD Mutation

Interventions

Type	Name	Description
DRUG	Sorafenib	Sorafenib a kinase inhibitor indicated for the treatment of Unresectable hepatocellular carcinoma; Advanced renal cell carcinoma
DRUG	Omacetaxine Mepesuccinate Injection	Omacetaxine Mepesuccinate is a pharmaceutical drug substance that is indicated for treatment of chronic myeloid leukemia (CML)

Timeline

• Start date: 2017-07-01
• Primary completion: 2020-02-01
• Completion: 2020-03-01
• First posted: 2017-05-31
• Last updated: 2020-03-30

Locations

1 site across 1 country: Hong Kong