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

• ClinicalTrials.gov Identifier: NCT00008359
• Recruitment Status: Completed
• First Posted: September 4, 2003
• Last Update Posted: January 18, 2013
• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by: Memorial Sloan Kettering Cancer Center

Study Description

Brief Summary:

RATIONALE: Caspofungin acetate or amphotericin B liposomal may be effective in preventing or controlling fever and neutropenia caused by chemotherapy, bone marrow transplantation, or peripheral stem cell transplantation. It is not yet known whether caspofungin acetate or amphotericin B liposomal is more effective for treating these side effects.

PURPOSE: Randomized phase III trial to compare the effectiveness of caspofungin acetate with that of amphotericin B liposomal in treating patients who have persistent fever and neutropenia after receiving anticancer therapy.

Condition or disease	Intervention/treatment	Phase
Cancer	Drug: caspofungin acetate; Drug: liposomal amphotericin B	Phase 3

Detailed Description:

OBJECTIVES:

• 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.
• Compare the incidence of nephrotoxicity in patients treated with these regimens.
• Compare the incidence of infusion-related adverse events within 1 hour of the infusion in patients treated with these regimens.
• 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.
• Compare incidence of required dose increase due to inadequate clinical response in patients treated with these regimens.
• Compare the time to resolution of fever in patients treated with these regimens.

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.

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Allocation: Randomized
• Masking: Double
• Primary Purpose: Supportive Care
• 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
• Study Start Date: August 2000
• Actual Primary Completion Date: March 2003

Arms and Interventions

Outcome Measures

Eligibility Criteria

• Ages Eligible for Study: 16 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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/mm^3 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

PATIENT CHARACTERISTICS:

Age:

• 16 and over

Performance status:

• Karnofsky 30-100%

Life expectancy:

• At least 5 days

Hematopoietic:

• Platelet count at least 5,000/mm^3
• 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

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

Contacts and Locations

Locations

United States, New York

Memorial Sloan-Kettering Cancer Center

New York, New York, United States, 10021

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

• Study Chair: Kent Sepkowitz, MD; Memorial Sloan Kettering Cancer Center

More Information

Publications of Results:

Walsh TJ, Teppler H, Donowitz GR, Maertens JA, Baden LR, Dmoszynska A, Cornely OA, Bourque MR, Lupinacci RJ, Sable CA, dePauw BE. Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med. 2004 Sep 30;351(14):1391-402.

• ClinicalTrials.gov Identifier: NCT00008359
• Other Study ID Numbers: 00-085; MSKCC-00085; MERCK-026-01; NCI-G00-1898
• First Posted: September 4, 2003
• Last Update Posted: January 18, 2013
• Last Verified: January 2013

Keywords provided by Memorial Sloan Kettering Cancer Center:

stage I adult Hodgkin lymphoma; stage II adult Hodgkin lymphoma; stage III adult Hodgkin lymphoma; stage IV adult Hodgkin lymphoma; stage IV breast cancer; stage IIIA breast cancer; monoclonal gammopathy of undetermined significance; stage IIIB breast cancer; recurrent adult Hodgkin lymphoma; stage I cutaneous T-cell non-Hodgkin lymphoma; stage II cutaneous T-cell non-Hodgkin lymphoma; stage III cutaneous T-cell non-Hodgkin lymphoma; stage IV cutaneous T-cell non-Hodgkin lymphoma; recurrent cutaneous T-cell non-Hodgkin lymphoma; isolated plasmacytoma of bone; extramedullary plasmacytoma; refractory multiple myeloma; stage II ovarian epithelial cancer; stage III ovarian epithelial cancer; stage IV ovarian epithelial cancer; recurrent ovarian epithelial cancer; disseminated neuroblastoma; recurrent neuroblastoma; recurrent Wilms tumor and other childhood kidney tumors; stage 0 chronic lymphocytic leukemia; Waldenstrom macroglobulinemia; stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; stage I chronic lymphocytic leukemia

Additional relevant MeSH terms:

Neutropenia; Agranulocytosis; Leukopenia; Leukocyte Disorders; Hematologic Diseases; Amphotericin B; Liposomal amphotericin B; Caspofungin; Amebicides; Antiprotozoal Agents; Antiparasitic Agents; Anti-Infective Agents; Anti-Bacterial Agents; Antifungal Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action