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

NCT ID: NCT00148148

Last Updated: 2008-01-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-05-31
• Study Completion Date: 2007-12-31

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

caspofungin

Intervention Type: DRUG

liposomal amphotericin B

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Adults (> or = 18 years of age) with granulocytopenia (absolute number of neutrophil granulocytes [ANC]: < or = 500/µL) who have undergone allogeneic haematopoeitic stem cell transplantation and immunosuppression with cyclosporin A
• Patients with persistent or recurrent fever (oral temperature > or = 38.0°C) and granulocytopenia (absolute neutrophil count < or = 500/µL) and adequate antibacterial therapy for > or = 36-48 hours, who need empirical antimycotic therapy
• Already inserted at least double-lumen central venous catheter for administration of drugs and extraction of plasma samples
• Sufficient renal and hepatic function
• Availability of negative pregnancy test and adequate contraceptive measures for female patients of childbearing age
• Availability of written informed consent from the patient or respectively from the legal representative after prior information

Exclusion Criteria

• Patients with active, possible or proven (MSG-EORTC criteria) invasive fungal infection at time of enrollment
• Pregnant or nursing patients
• Patients with pathological functional renal or hepatic parameters
• Patients with clinical or laboratory chemical evidence of active veno-occlusive disease (VOD)
• Hemodynamically unstable patients with a life expectancy of less than 5 days
• Patients undergoing co-medication with rifampicin, phenytoin, carbamazepine, phenobarbital, dexamethasone, efavirenz and nevirapine
• Patients with prior known serious reaction to echinocandin-antifungal formulation or documented allergy to amphotericin B
• Patients with other condition or illness which, in the estimation of the investigator, distorts the study results or leads to an additional risk for the patient
• Prior inclusion in the study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Gilead Sciences

INDUSTRY

Sponsor Role: collaborator

University Hospital Muenster

OTHER

Sponsor Role: lead

Principal Investigators

Andreas Groll, M.D.

Role: PRINCIPAL_INVESTIGATOR

University Hospital Muenster

Locations

KKS Münster University Hospital

Münster, North Rhine-Westphalia, Germany

Countries

Germany

Other Identifiers

BfArM 4021825

Identifier Type: -

Identifier Source: secondary_id

KKS-MS-005-KMT-10/03

Identifier Type: -

Identifier Source: org_study_id