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

NCT03170895 | Completed Phase 2 DMC

• 1 other identifier: AML008
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

AML; FLT3-ITD Mutation

Keywords

FLT3-ITD (+) Acute Myeloid Leukemia (AML)

Outcome Measures

Primary Outcomes (1)

• Complete remission

  No increase in blasts in BM or PB (\<5% of total nucleated cells), with absolute neutrophil count ≥ 1x109/L and platelet count ≥ 100 x109/L

  up to 16 weeks

Study Arms (1)

sorafenib and Omacetaxine Mepesuccinate

EXPERIMENTAL

The starting dose of sorafenib will be 400 mg twice daily. Sorafenib should be taken continuously throughout the treatment period unless there is no evidence of response at first assessment on day 28 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 sorafenib) in 28-day cycle. Sorafenib and OM 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.

Drug: Sorafenib; Drug: Omacetaxine Mepesuccinate Injection

Interventions

Sorafenib DRUG

Sorafenib a kinase inhibitor indicated for the treatment of Unresectable hepatocellular carcinoma; Advanced renal cell carcinoma

Also known as: NEXAVAR

sorafenib and Omacetaxine Mepesuccinate

Omacetaxine Mepesuccinate Injection DRUG

Omacetaxine Mepesuccinate is a pharmaceutical drug substance that is indicated for treatment of chronic myeloid leukemia (CML)

Also known as: homoharringtonine

sorafenib and Omacetaxine Mepesuccinate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of written informed consent approved by the Institutional Review Board (IRB).
• Age ≥18 years
• Documented primary AML or AML secondary to myelodysplastic syndrome (MDS), as defined by World Health Organization criteria
• At diagnosis or in morphological relapse after an initial remission or refractory after induction chemotherapy, with or without HSCT
• Documentation of FLT3-ITD in BM or blood with allelic burden of ≥ 20% as determined by the study site laboratory
• ECOG performance score 0-2
• Serum creatinine ≤1.5×upper limit of normal (ULN), or glomerular filtration rate \>25 mL/min, as calculated with the Cockcroft-Gault formula.
• Serum potassium, magnesium, and calcium (corrected for albumin) within institutional normal limits. Subjects with electrolytes outside the normal range will be eligible if these values are corrected upon retesting following any necessary supplementation.
• Total serum bilirubin ≤1.5×ULN.
• Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤ 2.5×ULN.

You may not qualify if:

• Acute promyelocytic leukemia (AML subtype M3)
• Prior treatment with any FLT3 inhibitors
• Known infection with human immunodeficiency virus, or active hepatitis B or C infection.
• Refusal of blood product transfusion.
• In a man whose sexual partner is a woman of childbearing potential, unwillingness or inability of the man or woman to use an acceptable contraceptive method for the entire study treatment period and for at least 3 months after study treatment completion
• In a heterosexually active woman of childbearing potential, unwillingness or inability to use an acceptable contraceptive method for the entire study treatment period and for at least 3 months after study treatment completion
• Pregnancy
• Female subjects must agree not to breastfeed at screening and throughout the study period, and for 45 days after the final study drug administration.

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

The University of Hong Kong

Hong Kong, Hong Kong

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Sorafenib; Homoharringtonine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Harringtonines; Alkaloids; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 4 or More Rings

Study Officials

• Anskar Leung, Professor

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: May 26, 2017
• First Posted: May 31, 2017
• Study Start: July 1, 2017
• Primary Completion: February 1, 2020
• Study Completion: March 1, 2020
• Last Updated: March 30, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)