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

NCT03135054 | Unknown Phase 2 DMC

• 1 other identifier: AML005
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

AML; FLT3-ITD Mutation

Keywords

FLT3-ITD (+) AML; Quizartinib, Omacetaxine mepesuccinate

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)

Combination

EXPERIMENTAL

Quizartinib is a second generation FLT3 inhibitors.The starting dose of quizartinib will be 30 mg/day oral 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 28 or progressive disease at any time during the treatment. Omacetaxine Mepesuccinate will be given at 1.5 mg/m2/day (maximum dose 3 mg) for 7 days (concurrently with quizartinib) in 28-day cycle.

Drug: Quizartinib; Drug: Omacetaxine Mepesuccinate Injection

Interventions

Quizartinib DRUG

Quizartinib is an oral FLT3 receptor tyrosine kinase inhibitor

Also known as: AC220

Combination

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

Combination

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
• Discontinuation of prior AML treatment ≥ 2 weeks before the start of QUIZOM (except hydroxyurea or other treatment to control leukocytosis).
• 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.
• Uncontrolled or significant cardiovascular disease, including:
• i. QTcF interval \> 450 msec ii. Bradycardia of ≤ 50 BPM iii. Diagnosed or suspected long QT syndrome, or known family history of long QT syndrome iv. History of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or torsade de pointes v. History of second or third degree heart block. Candidates with a history of heart block may be eligible if they currently have pacemakers, and have no history of fainting or clinically relevant arrhythmia with pacemakers.
• vi. Myocardial infarction within 6 months prior to screening vii. Uncontrolled angina pectoris within 6 months prior to screening viii. New York Heart Association (NYHA) Class 3 or 4 congestive heart failure ix. Uncontrolled hypertension x. Complete left or right bundle branch block
• 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

quizartinib; Homoharringtonine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Harringtonines; Alkaloids; Heterocyclic Compounds; 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: April 26, 2017
• First Posted: May 1, 2017
• Study Start: October 1, 2017
• Primary Completion: October 1, 2020
• Study Completion: October 1, 2021
• Last Updated: December 10, 2020

Record last verified: 2020-12

Locations

HK (1)