Prevention of Invasive Fungal Infections in Subjects Receiving Chemotherapy for Acute Lymphoblastic Leukemia (AmBiGuard)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01259713
First received: December 10, 2010
Last updated: February 14, 2014
Last verified: November 2013
  Purpose

The study aims to investigate whether prophylaxis with AmBisome can reduce the incidence of invasive fungal infections (IFIs) in patients with Acute Lymphoblastic Leukemia (ALL) who are undergoing their first remission induction.


Condition Intervention Phase
Invasive Fungal Disease
Drug: Liposomal amphotericin B
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase 3, Double-Blind, Multicenter, Randomized, Placebo-Controlled Study to Assess the Efficacy, Safety and Tolerability of Prophylactic Liposomal Amphotericin B (AmBisome®) for the Prevention of Invasive Fungal Infections (IFIs) in Subjects Receiving Remission-Induction Chemotherapy for Acute Lymphoblastic Leukemia (ALL)

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • proportion of subjects with proven or probable invasive fungal infections [ Time Frame: during remission induction chemotherapy for ALL (up to 12 weeks) ] [ Designated as safety issue: No ]
    Proportion of subjects diagnosed with proven or probable IFIs during remission induction chemotherapy for ALL. Diagnoses of proven or probable IFIs will be assessed according to EORTC/MSG criteria by an independent data review board (IDRB) who will be blinded to subject treatment assignment.


Secondary Outcome Measures:
  • pulmonary infiltrates [ Time Frame: during remission-induction chemotherapy (up to 12 weeks) ] [ Designated as safety issue: No ]
    The proportion of subjects with pulmonary infiltrates

  • subjects requiring antifungal treatment [ Time Frame: during remission-induction chemotherapy (up to 12 weeks) ] [ Designated as safety issue: No ]
    The proportion of subjects requiring antifungal treatment according to the protocol guidelines prior to starting consolidation chemotherapy

  • subject death due to fungal infection [ Time Frame: during remission-induction chemotherapy (up to 12 weeks) ] [ Designated as safety issue: No ]
    The proportion of subjects who die due to fungal infection; causality as assessed by the IDRB or Investigator

  • proven or probable IFIs by investigator [ Time Frame: during remission-induction chemotherapy (up to 12 weeks) ] [ Designated as safety issue: No ]
    The proportion of subjects diagnosed with proven or probable IFIs, according to the European Organization for Research and Treatment of Cancer (EORTC)/Mycoses Study Group (MSG) criteria as assessed by the investigator.


Enrollment: 355
Study Start Date: April 2011
Study Completion Date: January 2014
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AmBisome
Blinded AmBisome 5 mg/kg twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week).
Drug: Liposomal amphotericin B
5 mg/kg twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week during induction chemotherapy
Other Name: AmBisome
Placebo Comparator: Placebo
Blinded placebo twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week).
Drug: Placebo
Blinded placebo twice weekly administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Newly diagnosed ALL receiving an ALL chemotherapy regimen that typically induces at least 10 days of neutropenia defined as an absolute neutrophil count (ANC) < 500 cells/mm3 or 0.5x109 cells/L

    • Subjects with lymphoblastic lymphoma or any malignancy other than ALL are NOT eligible for this study.
  • Age ≥ 18 years
  • Able to have all screening tests performed quickly to ensure results can be obtained and evaluated before randomization so that the first dose of randomized study drug for IFI prophylaxis can be administered within 5 days of first remission-induction chemotherapy

    • pre-remission induction treatment (i.e. pre-phase) with a minimally or non myelosuppressive regimen for up to one week is not considered to constitute the beginning of remission induction chemotherapy
  • Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of any study procedures

Exclusion Criteria:

  • Known hypersensitivity to amphotericin B or AmBisome, the metabolites or formulation excipients, in particular known history of anaphylactic reaction to amphotericin B or AmBisome or any of its metabolites or formulation excipients
  • Known hypersensitivity to the excipients of the placebo formulation
  • Current fever (≥38°C) unless explained by noninfectious causes
  • Subjects with proven, probable or possible IFI (according to EORTC/MSG criteria) at screening or in subject history
  • Pulmonary infiltrates
  • Concomitant or previous treatment with an antifungal drug within the previous 30 days unless the plasma level is below the limit of detection or at least 5 half-lives of the antifungal has elapsed since the treatment was given
  • Serum creatinine > 2 x the upper limit of the normal range (ULN)
  • Grade 3 Liver function test results: alanine aminotransferase or aspartate aminotransferase > 5 x ULN; total bilirubin > 2.5 x ULN
  • Any severe co morbidity other than underlying hematological disease (ALL), which in the investigator's judgment may interfere with study evaluations or affect the subject's safety
  • Subjects who have taken any investigational drug in the last 30 days prior to screening, with the exception of ALL chemotherapy investigational products being used as part of the subject's current ALL treatment protocol
  • Pregnant or nursing females
  • Subjects with a prior history of a malignancy that was treated with a myeloablative chemotherapy regimen are NOT eligible for this study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01259713

Locations
United Kingdom
Gilead Sciences
Cambridge, United Kingdom, CB21 6GT
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Mike Hawkins, MD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01259713     History of Changes
Other Study ID Numbers: GS-EU-131-0247, 2010-019562-91
Study First Received: December 10, 2010
Last Updated: February 14, 2014
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Austria : Federal Ministry for Labour, Health, and Social Affairs
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: Ministry of Health
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: Ministry of Health and Welfare
Israel: Ministry of Health
Italy: National Institute of Health
Portugal: National Pharmacy and Medicines Institute
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Switzerland: Swissmedic
Turkey: Ministry of Health

Keywords provided by Gilead Sciences:
Ambisome
ALL
invasive fungal infection
prophylaxis
liposomal amphotericin B
Invasive fungal infection prophylaxis

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Mycoses
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Amphotericin B
Liposomal amphotericin B
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on April 16, 2014