Prevention of Invasive Fungal Infections (IFIs) in Subjec... | NCT01259713

NCT01259713

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

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No data is available for this block.

Document Section

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No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
2010-019562-91	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Liposomal amphotericin B	Experimental	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	Drug: Liposomal amphotericin B
Placebo	Placebo Comparator	Placebo to match liposomal amphotericin B 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	Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Liposomal amphotericin B	Drug	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 during induction chemotherapy

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Proven or Probable IFIs During Remission-induction Chemotherapy for Acute Lymphoblastic Leukemia (ALL)	Diagnoses of proven or probable invasive fungal infections (IFI) were assessed according to European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria by the independent data review board (IDRB) who were blinded to treatment assignment. The duration of remission-induction chemotherapy was defined as the period from the initiation of remission-induction chemotherapy administration to the start of consolidation or salvage therapy.	During remission-induction chemotherapy (average 7 weeks)

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Pulmonary Infiltrates According to the Central Image Reader		During remission-induction chemotherapy (average 7 weeks)
Percentage of Participants Diagnosed With Proven or Probable IFIs According to the EORTC/MSG Criteria, as Assessed by the Investigator

Eligibility Module

Eligibility 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 < 500 cells/mm^3 or 0.5 × 10^9 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
- Preremission induction treatment (ie, pre-phase) with a minimally or nonmyelosuppressive 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 European Organization for the Research and Treatment of Cancer/Mycoses Study Group (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 × the upper limit of the normal range (ULN)
Grade 3 Liver function test results: alanine aminotransferase or aspartate aminotransferase > 5 × 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.

Name	Affiliation	Role
Mike Hawkins, MD	Gilead Sciences	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Gilead Sciences		Cambridge		CB21 6GT	United Kingdom

ID	Title	Description
FG000	Liposomal Amphotericin B	Liposomal amphotericin B (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) during induction chemotherapy
FG001	Placebo	Placebo to match liposomal amphotericin B 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

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Liposomal Amphotericin B	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
BG001	Placebo

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With Proven or Probable IFIs During Remission-induction Chemotherapy for Acute Lymphoblastic Leukemia (ALL)

Diagnoses of proven or probable invasive fungal infections (IFI) were assessed according to European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria by the independent data review board (IDRB) who were blinded to treatment assignment.

The duration of remission-induction chemotherapy was defined as the period from the initiation of remission-induction chemotherapy administration to the start of consolidation or salvage therapy.

Intent-to-Treat (ITT) Analysis Set: participants in the safety analysis set who had no major violations of entrance criteria.

Posted

Number

percentage of participants

During remission-induction chemotherapy (average 7 weeks)

ID	Title	Description
OG000	Liposomal Amphotericin B	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

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Liposomal Amphotericin B	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

ID	Term
D009181	Mycoses
D001423	Bacterial Infections and Mycoses
D007239	Infections