Study to investigate the ability of AmBisome to prevent the development of serious invasive infections caused by fungi in patients diagnosed with acute lymphoblastic leukemia receiving the initial phase of their chemotherapy treatment.

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) - AmbiGUARD

Status

Active, not recruiting

Phases

Unknown

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2010-019562-91-AT

Enrollment

354

Registered

2010-11-16

Start date

2010-12-13

Completion date

Unknown

Last updated

2014-03-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Invasive fungal infections (IFI) in subjects with Acute Lymphoblastic Leukemia (ALL) undergoing remission induction chemotherapy MedDRA version: 14.1 Level: PT Classification code 10017533 Term: Fungal infection System Organ Class: 10021881 - Infections and infestations

Interventions

Trade Name: AmBisome Product Name: AmBisome Pharmaceutical Form: Powder for solution for infusion INN or Proposed INN: AMPHOTERICIN B CAS Number: 1397-89-3 Other descriptive name: AMPHOTERICIN B Conce

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Subjects must meet all of the following inclusion criteria to be eligible for participation in this study. • 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 Note: 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 no later than 5 days after the start of remission-induction chemotherapy Note: With respect to this timing, 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 biginning 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. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 344 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10

Exclusion criteria

Exclusion criteria: Subjects who meet any of the following exclusion criteria are not to be enrolled in this study. • 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 fungal causes have clearly been excluded, e.g. negative lung and sinus imaging, documented drug-fever, or response to anti-bacterial antibiotic treatment. • 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 (prior to starting remission induction chemotherapy): 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.

Design outcomes

Primary

Measure	Time frame
Main Objective: • To determine the prophylactic efficacy of AmBisome compared to placebo in preventing IFIs in subjects with ALL undergoing remission induction chemotherapy.;Secondary Objective: • To determine the safety and tolerability of prophylactic AmBisome in subjects with ALL undergoing remission induction chemotherapy. • To determine the impact of IFI prevention on the efficacy of remission induction chemotherapy in subjects with ALL. ;Primary end point(s): The primary objective of this study is to assess antifungal prophylaxis efficacy of AmBisome 5 mg/kg compared to placebo. The primary efficacy endpoint in support of this objective is the proportion of subjects with proven or probable IFIs during remission induction chemotherapy for ALL. ;Timepoint(s) of evaluation of this end point: Interim analysis for efficacy when 50% of subjects have completed the study. Final analysis when all subjects have completed the protocol defined last patient last visit.	—

Measure

Time frame

Main Objective: • To determine the prophylactic efficacy of AmBisome compared to placebo in preventing IFIs in subjects with ALL undergoing remission induction chemotherapy.;Secondary Objective: • To determine the safety and tolerability of prophylactic AmBisome in subjects with ALL undergoing remission induction chemotherapy. • To determine the impact of IFI prevention on the efficacy of remission induction chemotherapy in subjects with ALL. ;Primary end point(s): The primary objective of this study is to assess antifungal prophylaxis efficacy of AmBisome 5 mg/kg compared to placebo. The primary efficacy endpoint in support of this objective is the proportion of subjects with proven or probable IFIs during remission induction chemotherapy for ALL. ;Timepoint(s) of evaluation of this end point: Interim analysis for efficacy when 50% of subjects have completed the study. Final analysis when all subjects have completed the protocol defined last patient last visit.

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Secondary

Measure	Time frame
Secondary end point(s): Secondary efficacy endpoints to be assessed during remission induction chemotherapy for ALL are as follows: • The proportion of subjects with pulmonary infiltrates • The proportion of subjects diagnosed with proven or probable IFIs according to the EORTC/MSG criteria, as assessed by the investigator. • Time to diagnosis of proven or probable IFIs according to the EORTC/MSG criteria, as assessed by the IDRB • The proportion of subjects diagnosed with proven invasive fungal infections, according to the EORTC/MSG criteria as assessed by the IDRB. • The proportion of subjects diagnosed with probable invasive fungal infections, according to the EORTC/MSG criteria as assessed by the IDRB. • The proportion of subjects requiring antifungal treatment according to the protocol guidelines prior to starting consolidation chemotherapy. • The proportion of subjects who die due to fungal infection; causality as assessed by the IDRB. • The proportion of subjects who die due to fungal infection; causality as assessed by the investigator. Secondary endpoints to evaluate the potential impact of IFI prevention on the efficacy of remission induction chemotherapy for ALL are as follows: • The median duration of remission induction chemotherapy (i.e., the time from beginning of remission induction chemotherapy until the beginning of consolidation therapy) • The proportion of subjects with complete remission at the end of remission induction ;Timepoint(s) of evaluation of this end point: Final analysis when all subjects have completed the protocol defined last patient last visit.	—

Measure

Time frame

Secondary end point(s): Secondary efficacy endpoints to be assessed during remission induction chemotherapy for ALL are as follows: • The proportion of subjects with pulmonary infiltrates • The proportion of subjects diagnosed with proven or probable IFIs according to the EORTC/MSG criteria, as assessed by the investigator. • Time to diagnosis of proven or probable IFIs according to the EORTC/MSG criteria, as assessed by the IDRB • The proportion of subjects diagnosed with proven invasive fungal infections, according to the EORTC/MSG criteria as assessed by the IDRB. • The proportion of subjects diagnosed with probable invasive fungal infections, according to the EORTC/MSG criteria as assessed by the IDRB. • The proportion of subjects requiring antifungal treatment according to the protocol guidelines prior to starting consolidation chemotherapy. • The proportion of subjects who die due to fungal infection; causality as assessed by the IDRB. • The proportion of subjects who die due to fungal infection; causality as assessed by the investigator. Secondary endpoints to evaluate the potential impact of IFI prevention on the efficacy of remission induction chemotherapy for ALL are as follows: • The median duration of remission induction chemotherapy (i.e., the time from beginning of remission induction chemotherapy until the beginning of consolidation therapy) • The proportion of subjects with complete remission at the end of remission induction ;Timepoint(s) of evaluation of this end point: Final analysis when all subjects have completed the protocol defined last patient last visit.

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Countries

Argentina, Austria, Belgium, Brazil, France, Germany, Greece, Israel, Italy, Portugal, Spain, Switzerland, Turkey

Contacts

Public ContactClinical Trials Information

Gilead Sciences International Ltd

clinical.trials@gilead.com+4412238973004496

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026