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

NCT01615809 | Completed Phase 2 Results

• 1 other identifier: FSJD-ABELNEB-2010
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Invasive Pulmonary Aspergillosis; Lymphoblastic Leukaemia; Myeloblastic Leukaemia; Lymphoblastic Leukemia; Myeloblastic Leukemia

Keywords

Invasive pulmonary aspergillosis; IFI; Leukaemia; Leukemia; Pediatric; Paediatrics; Amphotericin B; Aspergillosis; Pulmonary Aspergillosis; Invasive Aspergillosis; Antifungal agents; Fungal infections; Invasive Fungal Infection

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events That Results in the Interruption of Treatment, as a Measure of Safety and Tolerability

  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).

  at the Baseline visit (week 1) and during the Last week of treatment, up to 6 weeks

Secondary Outcomes (2)

• Efficacy of Primary Prophylaxis With Nebulized Abelcet® on the Incidence of Invasive Pulmonary Aspergillosis

  at the Baseline visit (week 1) and at the end of the profilaxis treatment phase, up to 6 weeks

• Invasive Pulmonary Aspergillosis -Related Mortality During Primary Prophylaxis With Abelcet®.

  at the Baseline visit (week 1) and at the end of the profilaxis treatment phase, up to 6 weeks

Study Arms (1)

Amphotericin B (ABELCET®)

EXPERIMENTAL

Drug: AMPHOTERICIN B Dosage form: Abelcet® 5mg/ml administered by inhalation. Dosage: 10 ml (50 mg) for the first week with a frequency twice a week. Dosage: from the second week onwards 5 ml (25 mg) with a frequency of a minimum separation of 72 hours between doses, until the neutrophil count is greater than or equal to 1500 cells/mm3. Duration: 4-5 prophylaxis courses defined as each administration period during a neutropenia period, with a 4-6 weeks length considering the duration of neutropenia.

Drug: AMPHOTERICIN B

Interventions

AMPHOTERICIN B DRUG

The study drug will be administered by inhalation, to hospitalised patients or outpatients in the day hospital.

Also known as: Abelcet® 5 mg/ml

Amphotericin B (ABELCET®)

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• Probable or proven invasive pulmonary fungal infection before entering the trial.
• Previous chronic renal impairment or baseline serum creatinine \> 2.5 mg /dL
• Severe hepatic impairment.
• Moderate-severe asthma being treated pharmacologically.
• Antifungal treatment for filamentous fungi in the last 4 weeks.
• Participating or have participated in a clinical trial during the last 4 weeks.
• Mentally retarded
• Known allergy or hypersensitivity to the active ingredient of the study drug or to any of its excipients.
• 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.
• Pregnancy (in women of fertile age).
• 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.

Sponsors & Collaborators

• Fundació Sant Joan de Déu: lead
• Ministry of Health, Spain: collaborator

Study Sites (1)

Hospital Sant Joan de Déu

Esplugues de Llobregat, Barcelona, 08950, Spain

Location

Related Publications (15)

• Ascioglu S, Rex JH, de Pauw B, Bennett JE, Bille J, Crokaert F, Denning DW, Donnelly JP, Edwards JE, Erjavec Z, Fiere D, Lortholary O, Maertens J, Meis JF, Patterson TF, Ritter J, Selleslag D, Shah PM, Stevens DA, Walsh TJ; Invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer; Mycoses Study Group of the National Institute of Allergy and Infectious Diseases. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis. 2002 Jan 1;34(1):7-14. doi: 10.1086/323335. Epub 2001 Nov 26.

  PMID: 11731939 BACKGROUND

• Walsh TJ, Gonzalez C, Lyman CA, Chanock SJ, Pizzo PA. Invasive fungal infections in children: recent advances in diagnosis and treatment. Adv Pediatr Infect Dis. 1996;11:187-290. No abstract available.

  PMID: 8718464 BACKGROUND

• Blyth CC, Palasanthiran P, O'Brien TA. Antifungal therapy in children with invasive fungal infections: a systematic review. Pediatrics. 2007 Apr;119(4):772-84. doi: 10.1542/peds.2006-2931.

  PMID: 17403849 BACKGROUND

• Bodey GP, Anaissie EJ, Elting LS, Estey E, O'Brien S, Kantarjian H. Antifungal prophylaxis during remission induction therapy for acute leukemia fluconazole versus intravenous amphotericin B. Cancer. 1994 Apr 15;73(8):2099-106. doi: 10.1002/1097-0142(19940415)73:83.0.co;2-n.

  PMID: 8156515 BACKGROUND

• Lin SJ, Schranz J, Teutsch SM. Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis. 2001 Feb 1;32(3):358-66. doi: 10.1086/318483. Epub 2001 Jan 26.

  PMID: 11170942 BACKGROUND

• Perfect JR, Klotman ME, Gilbert CC, Crawford DD, Rosner GL, Wright KA, Peters WP. Prophylactic intravenous amphotericin B in neutropenic autologous bone marrow transplant recipients. J Infect Dis. 1992 May;165(5):891-7. doi: 10.1093/infdis/165.5.891.

  PMID: 1569339 BACKGROUND

• Walsh TJ, Hiemenz J, Pizzo PA. Evolving risk factors for invasive fungal infections--all neutropenic patients are not the same. Clin Infect Dis. 1994 May;18(5):793-8. doi: 10.1093/clinids/18.5.793. No abstract available.

  PMID: 8075273 BACKGROUND

• Walsh TJ, Hiemenz JW, Anaissie E. Recent progress and current problems in treatment of invasive fungal infections in neutropenic patients. Infect Dis Clin North Am. 1996 Jun;10(2):365-400. doi: 10.1016/s0891-5520(05)70303-2.

  PMID: 8803625 BACKGROUND

• Walsh TJ, Finberg RW, Arndt C, Hiemenz J, Schwartz C, Bodensteiner D, Pappas P, Seibel N, Greenberg RN, Dummer S, Schuster M, Holcenberg JS. Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. National Institute of Allergy and Infectious Diseases Mycoses Study Group. N Engl J Med. 1999 Mar 11;340(10):764-71. doi: 10.1056/NEJM199903113401004.

  PMID: 10072411 BACKGROUND

• Herbrecht R. The changing epidemiology of fungal infections: are the lipid-forms of amphotericin B an advance? Eur J Haematol Suppl. 1996;57:12-7. doi: 10.1111/j.1600-0609.1996.tb01347.x.

  PMID: 8706811 BACKGROUND

• Herbrecht R. Improving the outcome of invasive aspergillosis: new diagnostic tools and new therapeutic strategies. Ann Hematol. 2002;81 Suppl 2:S52-3. No abstract available.

  PMID: 12611078 BACKGROUND

• Nakagawa Y. [Prophylactic administration of fluconazole and itraconazole in febrile neutropenia associated with hematopoietic malignancy]. Jpn J Antibiot. 2006 Oct;59(5):407-9. No abstract available. Japanese.

  PMID: 17205660 BACKGROUND

• Boettcher H, Bewig B, Hirt SW, Moller F, Cremer J. Topical amphotericin B application in severe bronchial aspergillosis after lung transplantation: report of experiences in 3 cases. J Heart Lung Transplant. 2000 Dec;19(12):1224-7. doi: 10.1016/s1053-2498(00)00154-6.

  PMID: 11124494 BACKGROUND

• Alexander BD, Dodds Ashley ES, Addison RM, Alspaugh JA, Chao NJ, Perfect JR. Non-comparative evaluation of the safety of aerosolized amphotericin B lipid complex in patients undergoing allogeneic hematopoietic stem cell transplantation. Transpl Infect Dis. 2006 Mar;8(1):13-20. doi: 10.1111/j.1399-3062.2006.00125.x.

  PMID: 16623816 BACKGROUND

• Rijnders BJ, Cornelissen JJ, Slobbe L, Becker MJ, Doorduijn JK, Hop WC, Ruijgrok EJ, Lowenberg B, Vulto A, Lugtenburg PJ, de Marie S. Aerosolized liposomal amphotericin B for the prevention of invasive pulmonary aspergillosis during prolonged neutropenia: a randomized, placebo-controlled trial. Clin Infect Dis. 2008 May 1;46(9):1401-8. doi: 10.1086/586739.

  PMID: 18419443 BACKGROUND

MeSH Terms

Conditions

Invasive Pulmonary Aspergillosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelomonocytic, Acute; Leukemia; Aspergillosis; Pulmonary Aspergillosis; Mycoses; Invasive Fungal Infections

Interventions

Amphotericin B; liposomal amphotericin B

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections; Lung Diseases, Fungal; Lung Diseases; Respiratory Tract Diseases; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Rosa Maria morales Palau
• Organization: Fundaciò per la Recerca i la Docencia sant Joan de Deu

rmorales@fsjd.org

936009751

Study Officials

• Jesus Estella, PhMD

  Hospital Sant Joan de Deu

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2012
• First Posted: June 11, 2012
• Study Start: October 1, 2011
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: March 29, 2018
• Results First Posted: October 23, 2015

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will share

Locations

ES (1)