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

NCT01259713 | Completed Phase 3 Results DMC

• 2 other identifiers: GS-EU-131-02472010-019562-91
• Study Type: interventional
• Target: 355
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Invasive Fungal Disease

Keywords

Ambisome; ALL; invasive fungal infection; prophylaxis; liposomal amphotericin B; Invasive fungal infection prophylaxis

Outcome Measures

Primary Outcomes (1)

• 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 (8)

• 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

  During remission-induction chemotherapy (average 7 weeks)

• Time to Diagnosis of Proven or Probable IFIs According to the EORTC/MSG Criteria, as Assessed by the IDRB.

  During remission-induction chemotherapy (average 7 weeks)

• Percentage of Participants Requiring Antifungal Treatment During Remission-Induction Chemotherapy

  During remission-induction chemotherapy (average 7 weeks)

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

  During remission-induction chemotherapy (average 7 weeks)

Study Arms (2)

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

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

Also known as: AmBisome

Liposomal amphotericin B

Placebo DRUG

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (1)

Gilead Sciences

Cambridge, CB21 6GT, United Kingdom

Location

MeSH Terms

Conditions

Invasive Fungal Infections

Interventions

liposomal amphotericin B

Condition Hierarchy (Ancestors)

Mycoses; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Clinical Trial Disclosures
• Organization: Gilead Sciences, Inc.

ClinicalTrialDisclosures@gilead.com

Study Officials

• Mike Hawkins, MD

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2010
• First Posted: December 14, 2010
• Study Start: April 1, 2011
• Primary Completion: December 1, 2013
• Study Completion: January 1, 2014
• Last Updated: May 7, 2015
• Results First Posted: April 6, 2015

Record last verified: 2015-04

Locations

GB (1)