Clinical Trial: Nebulized Amphotericin B Lipid Complex in Invasive Pulmonary Aspergillosis in Paediatric Patients With Acute Leukaemia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase II Trial to Evaluate the Safety and Tolerability of Nebulised Amphotericin B Lipid Complex (ABELCET®) in the Prophylaxis of Invasive Pulmonary Aspergillosis D

Brief Summary: The trial evaluates the overall tolerability of the drug and the efficacy of aerosolised amphotericin B as a lipid complex (ABLC) for primary prophylaxis of invasive pulmonary aspergillosis (IPA) in pediatric patients with acute leukemia undergoing intensive chemotherapy.

Detailed Summary:

In recent years the incidence of invasive fungal infection (IFI) especially when caused by filamentous fungi has increased in patients with haematological malignancies and there exists an international consensus on diagnostic criteria. Despite diagnostic and therapeutic progress, invasive aspergillosis remains a major clinical problem of haematological patients, given the still high mortality rates and the huge economic cost of hospitalization of patients, which is attributable to aspergillosis. In addition to the morbidity and mortality rates, these infections interfere with the chemotherapy treatment plan with the risk of compromising the outcome of the antileukemic treatment.

In a few uncontrolled studies inhaled amphotericin B deoxycholate showed some benefit in haematological patients, however it was not effective in a large multicenter study with neutropenic patients. Based on the outcome of that clinical trial, the use of aerosolised amphotericin B deoxycholate in neutropenic patients was abandoned for nearly a decade. During this time the use of azole agents as drugs of choice for antifungal prophylaxis in high risk patients was consolidated. However, one of the main problems in the use of triazoles with activity against filamentous fungi (itraconazole, voriconazole, posaconazole) is drug-drug interactions due to their CYP3A4 inhibitory activity. One of the most serious interactions is that which occurs with vincristine, used throughout the treatment of acute lymphoblastic leukemia, and which has lead to reports of neurotoxicity due to metabolic inhibition.

ABLC (Abelcet®) belongs to the group of polyenes with antifungal activity against a broad spectrum of fungal species, including Aspergillus spp. The active component of ABELCET®, amphotericin B, acts by binding to sterols in the cell membrane of suscep
Sponsor: Fundació Sant Joan de Déu

Current Primary Outcome: Number of Participants With Adverse Events That Results in the Interruption of Treatment, as a Measure of Safety and Tolerability [ Time Frame: at the Baseline visit (week 1) and during the Last week of treatment, up to 6 weeks ]

is assessed by the proportion of patients who discontinue prophylactic treatment with Abelcet® due to an adverse event that is related or not to the study drug or for intolerability to it. The last week of treatment will have a different calendar for each participant, depending on the number of cicles needed by each patient (it has been anticipated up to 5 cicles of 2-6 weeks each).


Original Primary Outcome: Number of Participants With Adverse Events That Results in the Interruption of Treatment, as a Measure of Safety and Tolerability [ Time Frame: Baseline (week 1) and Last week of treatment (the number of the last week is variable by each patient, depending of the number of cicles needed by each patient) ]

The primary efficacy variable will be the proportion of patients who discontinue prophylactic treatment with Abelcet® due to an adverse event that is related or not to the study drug or for intolerability to it. The last week of treatment will have a different calendar for each participant, depending on the number of cicles needed by each patient (it has been anticipated up to 5 cicles of 2-6 weeks each).


Current Secondary Outcome:

  • Efficacy of Primary Prophylaxis With Nebulized Abelcet® on the Incidence of Invasive Pulmonary Aspergillosis (IPA) in Paediatric Patients With Acute Leukaemia (AL) Undergoing Intensive Chemotherapy [ Time Frame: at the Baseline visit (week 1) and at the end of the profilaxis treatment phase, up to 6 weeks ]
    The Incidence of IPA during the Abelcet® prophylactic treatment period was assessed by the relation between the number of patients with IPA and the number of patients on prophylaxis.
  • Invasive Pulmonary Aspergillosis (IPA)-Related Mortality During Primary Prophylaxis With Abelcet® in Paediatric Patients With (AL) Undergoing Intensive Chemotherapy. [ Time Frame: at the Baseline visit (week 1) and at the end of the profilaxis treatment phase, up to 6 weeks ]
    Percentage of deaths related to API during the prophylactic treatment period with Abelcet® in paediatric patients with (AL) undergoing intensive chemotherapy


Original Secondary Outcome:

  • Efficacy of Primary Prophylaxis With Nebulized Abelcet® on the Incidence of Invasive Pulmonary Aspergillosis (IPA) in Paediatric Patients With Acute Leukaemia (AL) Undergoing Intensive Chemotherapy [ Time Frame: Baseline (week 1) to end of profilaxis treatment phase (after 4-5 cycles=each cycle will have 2-6 weeks of duration) ]
    Will be assessed by: a) Proportion of discontinued drug administrations due to a treatment related adverse event or intolerability to treatment (number of discontinued administrations/ number of administrations started; b) Total number of IPA cases; c) Incidence of IPA during the Abelcet® prophylactic treatment period (number of patients with IPA/number of patients on prophylaxis); d) IPA incidence rate during the ABLC prophylactic treatment period.
  • Invasive Pulmonary Aspergillosis (IPA)-Related Mortality During Primary Prophylaxis With Abelcet® in Paediatric Patients With (AL) Undergoing Intensive Chemotherapy. [ Time Frame: Baseline (week 1) to end of profilaxis treatment phase (after 4-5 cycles=each cycle will have 2-6 weeks of duration) ]
    It will be assessed by: a) Mortality due to IPA; b)Percentage of deaths during the prophylactic treatment period and cause of death.


Information By: Fundació Sant Joan de Déu

Dates:
Date Received: June 4, 2012
Date Started: October 2011
Date Completion:
Last Updated: November 4, 2015
Last Verified: November 2015