Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Caspofungin Acetate Compared With Amphotericin B Liposomal in Treating Patients With Persistent Fever and Neutropenia Following Cancer Treatment

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Supportive care	Completed	16 and over	NCI, Pharmaceutical / Industry	MSKCC-00085 MERCK-026-01, NCI-G00-1898, NCT00008359

Objectives

1. Compare the number of successful treatment outcomes among patients treated with caspofungin acetate vs amphotericin B liposomal for persistent fever and neutropenia following cancer therapy, in terms of survival for 7 days after study drug, resolution of fever, treatment of any baseline fungal infection, absence of breakthrough fungal infection during and for 7 days after study drug, and absence of study drug discontinuation due to toxicity or lack of efficacy.
2. Compare the incidence of nephrotoxicity in patients treated with these regimens.
3. Compare the incidence of infusion-related adverse events within 1 hour of the infusion in patients treated with these regimens.
4. Compare the incidence of treatment discontinuation due to drug-related adverse events, frequency of drug-related events, number of breakthrough fungal infections, and number of successfully treated baseline fungal infections in patients treated with these regimens.
5. Compare incidence of required dose increase due to inadequate clinical response in patients treated with these regimens.
6. Compare the time to resolution of fever in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Leukemia, lymphoma, or other cancer that has been previously treated with chemotherapy or bone marrow or peripheral blood stem cell transplantation
• Absolute neutrophil count less than 500/mm³ for past 96 hours and not expected to recover in next 48 hours
• Received at least 96 hours of parenteral systemic antibacterial therapy
• Fever greater than 38.0 degrees Celsius
• Adequately managed bacterial infection allowed if all of the following are true:
  • Negative blood cultures
  • Received at least 5 days of antibiotics to which any bacterial isolates are sensitive
  • Surgical drainage of any abscess fluid or surgical debridement of infected tissues
  • Removal of infected catheters
• No invasive fungal infection
• Not previously enrolled on this study

Prior/Concurrent Therapy:

Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• See Disease Characteristics
• No concurrent investigational antineoplastic therapy

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• At least 10 days since prior parenteral amphotericin B
• At least 14 days since prior investigational antibiotic, antifungal, or immunosuppressive drug
• No concurrent rifampin or cyclosporine
• No other concurrent investigational antibiotic, antifungal, or immunosuppressive drug
• No concurrent alcohol

Patient Characteristics:

Age:

• 16 and over

Performance status:

• Karnofsky 30-100%

Life expectancy:

• At least 5 days

Hematopoietic:

• Platelet count at least 5,000/mm³
• INR no greater than 1.6 (no greater than 4.0 if receiving anticoagulants)

Hepatic:

• Bilirubin no greater than 3 times upper limit of normal (ULN)
• AST or ALT no greater than 5 times ULN
• Alkaline phosphatase no greater than 3 times ULN
• No acute hepatitis or cirrhosis

Renal:

• Not specified

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception
• No allergy, hypersensitivity, or prior serious reaction to any echinocandin antifungal or amphotericin B formulation
• No other condition or illness that would preclude study participation

Expected Enrollment

A total of 1060 patients (530 per arm) will be accrued for this study.

Outline

This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to high-risk (prior allogeneic bone marrow transplantation or prior chemotherapy for relapse of acute leukemia) vs low-risk and prior prophylactic antifungal therapy during chemotherapy (yes vs no). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive caspofungin acetate IV over 1 hour followed by placebo IV over 2 hours.
• Arm II: Patients receive placebo IV over 1 hour followed by amphotericin B liposomal IV over 2 hours.

Treatment repeats daily for up to 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed at 7 and 14 days after study drug discontinuation.

Walsh TJ, Teppler H, Donowitz GR, et al.: Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med 351 (14): 1391-402, 2004.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Kent Sepkowitz, MD, Protocol chair		Ph: 212-639-2441; 800-525-2225

Registry Information
Official Title		A Multicenter, Double-Blind, Randomized, Comparative Study To Evaluate The Safety, Tolerability, And Efficacy Of MK-0991 Versus (Amphotericin B) Liposome For Injection As Empirical Therapy In Patients With Persistent Fever And Neutropenia
Trial Start Date		2000-08-22
Trial Completion Date		2003-03-11
Registered in ClinicalTrials.gov		NCT00008359
Date Submitted to PDQ		2000-11-21
Information Last Verified		2009-12-02
NCI Grant/Contract Number		CA08748

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