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Anti-Infective Agents

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Amphotericin B

Liposomal amphotericin B

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Antifungal Agents

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

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

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

Placebo to match liposomal amphotericin B administered by IV route over 2 hours twice weekly (each dose separated alternately by 2 and 3 days each week) during induction chemotherapy

Placebo

Mike Hawkins, MD

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

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

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)

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.

Time to diagnosis of proven or probable IFIs is presented as the median (Q1,Q3) days to diagnosis of those participants who experienced a proven or probable IFI. Median was not reached if \< 50% of participants had an event; Q1 was not reached if \< 25% of participants had an event; Q3 was not reached if \< 75% of participants had an event.

This endpoint was to evaluate the potential impact of IFI prevention on the efficacy of remission-induction chemotherapy for ALL.

Gilead Sciences

Safety Analysis Set; participants who were randomized and received at least 1 dose of study drug.

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.

Liposomal Amphotericin B

Total

Age, Continuous

≤ 25 years

> 25 to ≤ 60 years

> 60 years

Age, Customized

Sex: Female, Male

Asian

Black

White

Not Permitted

Other

Race/Ethnicity, Customized

Germany

Italy

France

Belgium

Spain

Greece

Portugal

Turkey

Austria

Israel

Switzerland

Brazil

Argentina

Region of Enrollment

Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug.

Clinical Trial Disclosures

A two-group Cochran-Mantel-Haenszel (CMH) test with a 0.05 two-sided significance level and 2:1 allocation of 354 randomized subjects (236 AmBisome, 118 placebo) would have 81% power to detect a relative reduction of 75% if the rate of IFI is 10% in the placebo group (based on unpublished data from the German Multicenter Acute Lymphoblastic Leukemia Working Group (GMALL) and consistent with the published rate of 16.4% in patients with hematological malignancies undergoing remission induction).

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

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

Percentage of Participants With Pulmonary Infiltrates According to the Central Image Reader

Percentage of Participants 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.

Percentage of Participants Requiring Antifungal Treatment During Remission-Induction Chemotherapy

Percentage of Participants Who Died Due to Fungal Infection; Causality as Assessed by the IDRB.

Percentage of Participants Who Died Due to Fungal Infection; Causality as Assessed by the Investigator.

Time From Beginning of Remission-induction Chemotherapy Until the Beginning of Consolidation Therapy

Participants were not stratified for leukemia risk.

Percentage of Participants With Complete Remission at the End of Remission Induction

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

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Prevention of Invasive Fungal Infections (IFIs) in Subjects Receiving Chemotherapy for Acute Lymphoblastic Leukemia	NCT01259713	Invasive Fungal...	Liposomal ampho... Placebo	18 Years -	Gilead Sciences
Prevention of Invasive Fungal Infections (IFIs) in Subjects Receiving Chemotherapy for Acute Lymphoblastic Leukemia	NCT01259713	Invasive Fungal...	Liposomal ampho... Placebo	18 Years -	Gilead Sciences

Spots Global Cancer Trial Database for invasive fungal infection prophylaxis