Investigating the role of targeted therapy Sorafenib - the Fms-like tyrosine kinase 3 (FLT3) inhibitor, in combination with intensive chemotherapy, for previously untreated adult patients with Acute Myeloid Leukaemia (AML) with FLT3 mutations. A Phase II randomised placebo-controlled multi-centre study

Phase 2

Completed

• Conditions: Previously untreated adult acute myeloid leukaemia (AML) with FLT3-ITD mutation.; Cancer - Leukaemia - Acute leukaemia

• Registration Number: ACTRN12611001112954
• Lead Sponsor: eukaemia Foundation of Australia

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-10-25
• Study Completion: 2020-09-08
• Last Update Posted: 21 August 2023

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 98

Inclusion Criteria

A morphological diagnosis of AML by WHO 2008 criteria, confirmed by special stains, immunophenotyping and, if available, cytogenetics. All clinico-pathological subtypes will be eligible, except for AML with t(15;17) or variants.

Patients with secondary and therapy related AML are eligible

FLT3-ITD mutation with an allelic mutant:wild-type ratio of = 0.05

Age 15 to 65 years inclusive.

ECOG performance status 0 to 2 inclusive

Absence of serious cardiac, pulmonary, hepatic or renal disease. A serum creatinine <1.5 times the upper limit of normal (ULN) and serum bilirubin < 2.5 times the upper limit of normal, is required for eligibility

Normal left ventricular ejection fraction, according to institutional criteria.

No previous treatment for AML or history of cancer (other than basal cell skin cancer or carcinoma of the cervix in situ, or other localised cancer treated by surgical excision only more than 5 years earlier without evidence of recurrence in the intervening period)

No contraindication to the use of the study drugs

Treatment must be given at an affiliated ALLG centre, with approval of the protocol by the institution’s Human Research Ethics Committee, or equivalent body

Written informed consent must be obtained from each patient prior to registration and start of treatment

Exclusion Criteria

Clinically active CNS leukaemia

Prior chemotherapy for AML (other than hydroxyurea ceased at least 24 hrs prior)

Known HIV positive

Known active hepatitis B or C, or any other active liver disease

Patients with parenchymal abnormality on screening chest x-ray must have no evidence of pulmonary infection on chest tomography (CT) prior to starting remission induction therapy

Any major surgery or radiation therapy within 4 weeks prior to study entry

Serious concomitant illnesses (for example, pulmonary infiltrate, unstable angina or myocardial infarction or stroke within 3 months prior to study entry, congestive heart failure AHA class 2 or greater, uncontrolled hypertension, uncontrolled diabetes, actively bleeding gastric ulcer, etc.), which in the investigator’s opinion would not make the patient a good candidate for the trial

Pregnant or breastfeeding

Any other known condition (e.g., familial, sociological, or geographical) or behaviour (including substance dependence or abuse, psychological or psychiatric illness), which in the investigator’s opinion would make the patient a poor candidate for the trial.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To determine 2 year event-free survival (EFS) in untreated adult AML (age 15-65) with FLT3 ITD mutation administered the FLT3 inhibitor Sorafenib compared to a placebo control group not receiving Sorafenib.<br><br>The primary endpoint will be the Event-free survival (EFS), measured from the date of randomisation until the date of death from any cause, AML relapse or treatment failure. If the patient does not achieve a CR, EFS is defined as the point of progression or death, whichever comes first. Patients with none of these events at the close-out date will have their EFS censored at the close-out date. The atients with none of these events and who were also deemed to be lost to follow-up before the close-out date, will have their EFS censored at the date they were last known to be alive.[Event-free survival after 2 years from registration.]