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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Ministry of Health, Spain
Information provided by (Responsible Party):
Fundació Sant Joan de Déu
ClinicalTrials.gov Identifier:
NCT01615809
First received: June 4, 2012
Last updated: December 3, 2013
Last verified: December 2013
  Purpose

The aim of this clinical trial is to assess 25-30 patients of both sexes, between the ages of 3 to 18 years, who are receiving intensive chemotherapy treatment for acute myeloblastic or lymphoblastic leukemia (AML, ALL) and will be treated with aerosolised (inhalation) amphotericin B lipid complex (Abelcet®) as a prophylactic for invasive pulmonary aspergillosis during prolonged neutropenia.

The trial will evaluate the overall tolerability of the drug and the efficacy of aerosolised ABLC for primary prophylaxis of invasive pulmonary aspergillosis (IPA). In the event that the working hypothesis is confirmed, aerosolised ABLC treatment would be an effective, safe and reliable prophylactic option for IPA. It would offer an alternative to the systemic administration of antifungal triazoles without affecting the antileukemic treatment in pediatric patients with AL.


Condition Intervention Phase
Invasive Pulmonary Aspergillosis
Lymphoblastic Leukaemia
Myeloblastic Leukaemia
Lymphoblastic Leukemia
Myeloblastic Leukemia
Drug: AMPHOTERICIN B
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II CT to Evaluate the Safety and Tolerability of Nebulised Amphotericin B Lipid Complex (ABELCET®) in the Prophylaxis of Invasive Pulmonary Aspergillosis During Prolonged Neutropenia in Paediatric Patients With Acute Leukaemia.

Resource links provided by NLM:


Further study details as provided by Fundació Sant Joan de Déu:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]
    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).


Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: Yes ]
    It will be assessed by: a) Mortality due to IPA; b)Percentage of deaths during the prophylactic treatment period and cause of death.


Estimated Enrollment: 30
Study Start Date: October 2011
Estimated Study Completion Date: January 2014
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Amphotericin B (ABELCET®)
Patients fulfilling inclusion criteria and those giving the general informed consent for the study will initiate nebulized Amphotericin B prophylaxis treatment, twice a week, during neutropenia periods (coincident with intensive chemotherapy treatment).
Drug: AMPHOTERICIN B
The study drug will be administered by inhalation, to hospitalised patients or outpatients in the day hospital.The administration regimen for each Abelcet® nebulization will be 10 ml (50 mg) twice a week for the first week, and then from the second week onwards it will be 5 ml (25 mg) with a minimum separation of 72 hours between doses, until the neutrophil count is greater than or equal to 1500 cells/mm3.
Other Name: Abelcet® 5 mg/ml

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   3 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age: patients between 3 and 18 years.
  2. Diagnosis of myeloblastic or lymphoblastic AL during intensive chemotherapy.
  3. Informed consent of parents/guardians and/or assent of the patient has been obtained.

Exclusion Criteria:

  1. Probable or proven invasive pulmonary fungal infection before entering the trial.
  2. Previous chronic renal impairment or baseline serum creatinine > 2.5 mg /dL
  3. Severe hepatic impairment.
  4. Moderate-severe asthma being treated pharmacologically.
  5. Antifungal treatment for filamentous fungi in the last 4 weeks.
  6. Participating or have participated in a clinical trial during the last 4 weeks.
  7. Mentally retarded
  8. Known allergy or hypersensitivity to the active ingredient of the study drug or to any of its excipients.
  9. Any serious concomitant disease that in the investigator's opinion could compromise the completion of the trial or affect the patient's tolerability to this treatment.
  10. Pregnancy (in women of fertile age).
  11. Breast-feeding.

Patients are defined as having probable IFI when their radiological image is suggestive of fungal infection and they have positive antigenemia for Aspergillus. IFI would be proven when the presence of Aspergillus is confirmed in aspirate culture or by lung biopsy.

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01615809

Locations
Spain
Hospital Sant Joan de Déu
Esplugues de Llobregat, Barcelona, Spain, 08950
Sponsors and Collaborators
Fundació Sant Joan de Déu
Ministry of Health, Spain
Investigators
Principal Investigator: Jesus Estella, PhMD Hospital Sant Joan de Deu
  More Information

Additional Information:
Publications:

Responsible Party: Fundació Sant Joan de Déu
ClinicalTrials.gov Identifier: NCT01615809     History of Changes
Other Study ID Numbers: FSJD-ABELNEB-2010
Study First Received: June 4, 2012
Last Updated: December 3, 2013
Health Authority: Spain: Spanish Agency of Medicines
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Spain: Ministry of Health

Keywords provided by Fundació Sant Joan de Déu:
Invasive pulmonary aspergillosis
IFI
Leukaemia
Leukemia
Pediatric
Paediatrics
Amphotericin B
Aspergillosis
Pulmonary Aspergillosis
Invasive Aspergillosis
Antifungal agents
Fungal infections
Invasive Fungal Infection

Additional relevant MeSH terms:
Aspergillosis
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid
Invasive Pulmonary Aspergillosis
Pulmonary Aspergillosis
Hyalohyphomycosis
Dermatomycoses
Skin Diseases, Infectious
Infection
Mycoses
Skin Diseases
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lung Diseases, Fungal
Lung Diseases
Respiratory Tract Diseases
Amphotericin B
Liposomal amphotericin B
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 27, 2014