Study aiming at proving the efficacy, safety and tolerability of inhaled Itraconazole in the prevention of Invasive Mould Disease (infections of the lungs by fungi) in patients with Acute Leukaemia and Neutropaenia (abnormally low concentration of neutrophils in the blood)
- Conditions
- prevention of invasive mould diseaseMedDRA version: 20.0Level: LLTClassification code 10003488Term: AspergillosisSystem Organ Class: 100000004862Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2019-002408-42-PL
- Lead Sponsor
- ABORATOIRES SMB S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 462
1.Male or female patients =12 years of age
2.Patients with new or relapsed ALL or AML who cannot receive posaconazole for any reason and who are to undergo remission-induction chemotherapy
3.Current neutropaenia resulting from the diagnosis of new or relapsed acute leukaemia or patients with expected neutropaenia for at least 10 days (an absolute neutrophil count <500 cell/mm3 or 0.5 x 109 cell/L) following remission-induction chemotherapy
4.Able to have all Screening tests performed quickly to ensure results can be obtained and evaluated before randomisation, so that the first dose of study drug for the prevention of IMD can be administered as soon as possible within 5 days of the start of remission-induction chemotherapy. In ALL patients, as soon as possible within 5 days of the start of remission-induction chemotherapy means as soon as possible within 5 days of the start of high-dose steroid therapy.
5.Able to comply with all study procedures, including the use of inhalers
6.If patient is a female of childbearing potential (FOCP), patient must agree to abstain from sexual intercourse or to use an effective means of birth control (oral contraceptives, intrauterine device [IUD], condoms and spermicides, vaginal ring, hormonal patch, implants), as determined by the Investigator from the first dose of study drug until 100 days following the last dose of study drug. A female patient is considered to be of childbearing potential if she has reached menarche and a) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries), or b) has not been postmenopausal for 12 consecutive months (i.e., has had menses at any time during the preceding 12 months). Female patients of childbearing potential must also provide a negative blood pregnancy test at the Screening Visit. Male patients must be vasectomised, abstain from sexual intercourse, or agree to use barrier contraception (condom with spermicide), and also agree not to donate sperm from the first dose of study drug until 100 days following the last dose of study drug.
7.Patients (and/or the patient’s parents or legally authorised representatives) must give written informed consent to participate in the study by signing and dating the Informed Consent Form (ICF)/Adolescent Assent Form (to be obtained prior to initiation of any study procedure)
Are the trial subjects under 18? yes
Number of subjects for this age range: 23
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 339
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100
1.Proven, probable, or possible IMD (according to 2019 European Organisation for Research and Treatment of Cancer/Mycoses Study Group Education and Research Consortium [EORTC/MSGERC] criteria at Screening or in the patient's medical history
2.Pulmonary complications or active infiltrates associated with an ongoing pulmonary disease assessed by a chest CT
3.Patients with ventricular dysfunction defined as ejection fraction <55% at Screening
4.Concomitant or previous treatment with a mould-active antifungal drug within 30 days, unless the plasma level is below the limit of detection or =5 half-lives of the antifungal has elapsed since the treatment was given.
5.Participating in another clinical trial with exposure to any investigational drug within 30 days prior to Screening, with the exception of the current anti-leukemic treatment
6.Pregnant or nursing females
7.Any severe co-morbidity other than underlying haematological disease that may interfere with study procedures or affect the patient’s safety
8.Grade 3 aspartate aminotransferase (ASAT >5 × upper limit of normal (ULN), alanine aminotransferase (ALAT >5 × ULN, or total bilirubin >3 × ULN.
9.Any contraindication or hypersensitivity to the use of fluconazole or ITZ or the excipient (mannitol) in the study drug and placebo formulations
10.Co-administration of astemizole, atorvastatin, bepridil, cisapride, dihydroergotamine, dofetilide, eletriptan, ergometrine (erginovine), ergotamine, erythromycin, levacetylmethadol (levomethadyl), lovastatin, methylergometrine (methylergonovine), midazolam, mizolastine, nisoldipine, pimozide, quinidine, sertindole, simvastatin, terfenadine and triazolam.
11.Abnormal QT interval corrected by Fridericia (QTcF): males >450 ms and females >470 ms
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Timepoint(s) of evaluation of this end point: End of treatment;Main Objective: To investigate whether prophylaxis with ITZ DPI can reduce the incidence rate of IMD in patients with acute leukaemia undergoing remission-induction chemotherapy;Secondary Objective: -To investigate the safety and tolerability of ITZ DPI in patients with acute leukaemia undergoing remission-induction chemotherapy<br>-To evaluate the PK of ITZ DPI in patients with acute leukaemia undergoing remission-induction chemotherapy<br>;Primary end point(s): The primary efficacy endpoint is the:<br>•Proportion of patients with proven or probable IMD at EOT. Diagnoses of proven or probable IMD will be evaluated according to 2019 EORTC/MSGERC criteria, as assessed by the Independent Data Review Board (IDRB) that will be blinded to treatment assignment.<br>
- Secondary Outcome Measures
Name Time Method