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

Sponsor:	Memorial Sloan-Kettering Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00008359

Purpose

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	Intervention	Phase
Cancer	Drug: caspofungin acetate Drug: liposomal amphotericin B	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Masking: Double-Blind 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

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer cyclic neutropenia essential thrombocythemia neuroblastoma polycythemia vera primary myelofibrosis

MedlinePlus related topics: Acute Lymphocytic Leukemia Acute Myeloid Leukemia Cancer Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia Fever Fungal Infections Hodgkin Disease Leukemia Lymphoma Multiple Myeloma Myelodysplastic Syndromes Neuroblastoma

Drug Information available for: Caspofungin Caspofungin Acetate Amphotericin B

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:	August 2000
Primary Completion Date:	March 2003 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00008359

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

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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 History of Changes
Other Study ID Numbers:	CDR0000068400, MSKCC-00085, MERCK-026-01, NCI-G00-1898
Study First Received:	January 6, 2001
Last Updated:	August 20, 2011
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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:

Lymphoma, Non-Hodgkin
Neutropenia
Lymphoma, Large-Cell, Immunoblastic
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Agranulocytosis
Leukopenia
Leukocyte Disorders

Hematologic Diseases
Amphotericin B
Liposomal amphotericin B
Caspofungin
Echinocandins
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on February 09, 2012