NCT00148148

A Study of Caspofungin, Liposomal Amphotericin B or the Combination of Both for Patients After Stem-Cell Transplantation

Phase II Randomised Study of the Safety, Efficacy and Pharmacokinetics of Caspofungin (CAS), Liposomal Amphotericin B (LAMB) or the Combination of Caspofungin With Liposomal Amphotericin B for Patients After Stem-Cell Transplantation

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 75 (estimated)
• Sponsor: University Hospital Muenster · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The study compares the safety, efficacy and pharmacokinetics of caspofungin, liposomal amphotericin B or the combination of both in the antifungal treatment of adult patients after allogeneic haematopoietic stem-cell transplantation with granulocytopenia and persistent i.g. recurrent fever under adequate antibacterial therapy.

Detailed description

This is an open, randomised, three-arm multicenter phase II clinical trial investigating the safety, tolerance and plasma pharmacokinetics of caspofungin, liposomal amphotericin B and the combination of both agents as empirical antifungal therapy in adult patients following allogeneic hematopoietic stem cell transplantation. Eligible patients are those with profound granulocytopenia (≤ 500 neutrophil granulocytes) and persistent or recurrent fever despite broad-spectrum antibacterial therapy of a minimum of 36-48 hours duration. Patients are stratified according to the type of the transplantation (human leukocyte antigen \[HLA\] matched/related versus HLA-mismatched/unrelated) and randomized into one of the following treatment arms: Caspofungin alone (50 mg/day with a loading dose of 70 mg on day 1), liposomal amphotericin B alone (3 mg/kg/day), or the combination of caspofungin and liposomal amphotericin B (similar dosages as in the single-drug treatment arms). Caspofungin and liposomal amphotericin B are administered once daily as an intravenous infusion. Serial plasma samples for determination of pharmacokinetic parameters are collected on days one and four of treatment. Safety and tolerance of the randomised intervention are evaluated daily, following the last dose of study drug and at 14 days after last dose of study drug according to current NCI-CTC criteria. Antifungal efficacy and survival are evaluated following the last dose of study drug and at 14 days after the last dose of study drug. Treatment with study drug is continued until either: 1. treatment limiting intolerance or toxicity; 2. hematopoietic engraftment (≥ 500 neutrophil granulocytes on three consecutive days) and defervescence; or 3. the occurrence of a probable or proven invasive fungal infection using current EORTC/MSG criteria. Febrile granulocytopenic patients with probable or proven invasive fungal infections are not eligible for this study. Patients who develop a probable or proven breakthrough infection are taken off study and receive standard therapy. Breakthrough infections are defined as probable or proven invasive fungal infections that occur during treatment with study medication. Twenty-five patients with a minimum duration of treatment of four days will be randomised per study arm. Patients who receive at least one dose of study drug are eligible for analysis of safety, tolerance and pharmacokinetics. For the analysis of the secondary endpoints of antifungal efficacy and survival, two separate cohorts will be analysed. These include: 1. patients who received at least one dose of study drug; and 2. patients who received ≥ four doses of study drug.

Conditions

• Hematopoietic Stem Cell Transplantation
• Fungus Diseases

Interventions

Type	Name	Description
DRUG	caspofungin
DRUG	liposomal amphotericin B

Timeline

• Start date: 2004-05-01
• Completion: 2007-12-01
• First posted: 2005-09-07
• Last updated: 2008-01-16

Locations

1 site across 1 country: Germany