Clinical Trial: Ambisome and Management of Culture-negative Neutropenic Fever Unresponsive to Antibiotics

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Phase III Study of 3 Sequential Doses (10 mg/kg, 5 mg/kg, and 5 mg/kg) vs 3 mg/kg/Day of AmBisome® in the Management of Culture-negative Neutropenic Fever Unresponsiv

Brief Summary: Administration of a single high dose (10 mg/kg) of AmBisome® no later than 72 hours after ARNF onset followed by two 5 mg/kg doses on days 2 and 5 may provide sustained tissue levels of amphotericin B that are as mycologically effective as those provided after administering the standard daily dose of 3 mg/kg/day. The new dosing regimen is anticipated to be equally clinically effective compared with the standard AmBisome® regimen when given for the duration of neutropenic fever in patients with ARNF. In addition, the degree and incidence of nephrotoxicity are predicted to be lower with the 3 sequential dose regimen compared to daily dosing with 3 mg/kg because of the lower cumulative dosage (20 mg/kg versus 42 mg/kg, respectively), which is 1 contributing factor for the development of acute renal failure. Furthermore, the lower cumulative dose may be a cost-effective strategy for the treatment of patients with ARNF.

Detailed Summary:

This is a phase III, multicenter, randomized, open-label study. One center in the United Arab Emirates and 1 center in Turkey will participate in this trial and approximately 50 patients will be recruited.

Patients will be adults with hematological malignancies undergoing chemotherapy for leukemia or lymphoma. These patients will be treated with AmBisome® until resolution of fever and neutropenia or for a maximum of 14 days.

Patients will be randomized to receive AmBisome 10 mg/kg on treatment day 0 followed by 5 mg/kg on days 2 and 5 or AmBisome 3 mg/kg/day for 14 days. Study medication will be administered during the period of ARNF until resolution of fever and neutropenia and/or a minimum of 14 days. At the end of the 14-day trial period, each patient will be classified as having responded or not responded to the treatment according to the criteria for response given below.

Patients will be examined daily for evidence of drug toxicity or intolerance and for the development of an IFI. Vital signs will be recorded every 6 hours if the patient is stable or more frequently if there is evidence of clinical deterioration. In the event of a clinical IFI (i.e., development of a halo sign or positive fungal blood cultures), the patient will be withdrawn from the study, classified as treatment failure, and receive antifungal treatment with either caspofungin or voriconazole. Daily clinical observations will ensure rapid detection of such an event in accordance with standard IDSA guidelines4. Patients who show clinical deterioration (i.e., increasing dyspnea, hypotension) but exhibit no definite evidence of an IFI may also be classified as treatment failures. Patients with evidence of biochemical and/or clinical drug toxicity will be withdrawn from the study and appropriate ma
Sponsor: Gilead Sciences

Current Primary Outcome: PK Profile of the dosing regimen under study (AUC, Cmax, Cmin, and etc.) [ Time Frame: throughout ]

Original Primary Outcome: PK Profile of the dosing regimen under study (AUC, Cmax, Cmin, and etc.)

Current Secondary Outcome:

  • Proportion of patients with defervescence (temperature < 38°C for ≥ 48 hours) occurring during neutropenia [ Time Frame: throughout ]
  • Time to defervescence from start of study entry and from time fever first recorded [ Time Frame: throughout ]
  • Proportion of patients with emergence of an IFI during AmBisome® treatment [ Time Frame: throughout ]
  • Survival during hospital admission [ Time Frame: throughout ]
  • Survival at 14 days after study initiation [ Time Frame: Day 14 ]
  • Proportion of patients with treatment-emergent adverse events [ Time Frame: throughout ]
  • Proportion of patients with treatment-emergent adverse events related to study drug [ Time Frame: throughout ]
  • Proportion of patients with post-baseline toxicity grading changes in each laboratory test (those graded according to the protocol). [ Time Frame: throughout ]


Original Secondary Outcome:

  • Efficacy:
  • Proportion of patients with defervescence (temperature < 38°C for ≥ 48 hours) occurring during neutropenia
  • Time to defervescence from start of study entry and from time fever first recorded
  • Proportion of patients with emergence of an IFI during AmBisome® treatment
  • Survival during hospital admission
  • Survival at 14 days after study initiation
  • Safety:
  • Proportion of patients with treatment-emergent adverse events
  • Proportion of patients with treatment-emergent adverse events related to study drug
  • Proportion of patients with post-baseline toxicity grading changes in each laboratory test (those graded according to the protocol).


Information By: Gilead Sciences

Dates:
Date Received: January 8, 2007
Date Started: March 2007
Date Completion:
Last Updated: March 9, 2011
Last Verified: April 2008