Clinical trial NCT00008359: Caspofungin Acetate Compared With Amphotericin B Liposomal in Treating Patients With Persistent Fever and Neutropenia Following Cancer Treatment
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cancer
Keywords: 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
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
refractory chronic lymphocytic leukemia
small intestine lymphoma
stage III malignant testicular germ cell tumor
recurrent malignant testicular germ cell tumor
unspecified adult solid tumor, protocol specific
chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
meningeal chronic myelogenous leukemia
adult acute myeloid leukemia in remission
adult acute lymphoblastic leukemia in remission
polycythemia vera
primary myelofibrosis
essential thrombocythemia
fever, sweats, and hot flashes
testicular embryonal carcinoma
testicular choriocarcinoma
testicular teratoma
testicular yolk sac tumor
testicular embryonal carcinoma and teratoma
testicular embryonal carcinoma and teratoma with seminoma
testicular embryonal carcinoma and yolk sac tumor
testicular embryonal carcinoma and yolk sac tumor with seminoma
testicular embryonal carcinoma and seminoma
testicular yolk sac tumor and teratoma
testicular yolk sac tumor and teratoma with seminoma
testicular choriocarcinoma and yolk sac tumor
testicular choriocarcinoma and embryonal carcinoma
testicular choriocarcinoma and teratoma
testicular choriocarcinoma and seminoma
progressive hairy cell leukemia, initial treatment
refractory hairy cell leukemia
stage I grade 1 follicular lymphoma
stage I grade 2 follicular lymphoma
stage I grade 3 follicular lymphoma
stage I adult diffuse small cleaved cell lymphoma
stage I adult diffuse mixed cell lymphoma
stage I adult diffuse large cell lymphoma
stage I adult immunoblastic large cell lymphoma
stage I adult lymphoblastic lymphoma
stage I adult Burkitt lymphoma
recurrent ovarian germ cell tumor
chronic myelomonocytic leukemia
T-cell large granular lymphocyte leukemia
ovarian yolk sac tumor
ovarian embryonal carcinoma
ovarian polyembryoma
ovarian choriocarcinoma
ovarian immature teratoma
ovarian mature teratoma
ovarian monodermal and highly specialized teratoma
ovarian mixed germ cell tumor
acute undifferentiated leukemia
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III adult Burkitt lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV adult Burkitt lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
stage I adult T-cell leukemia/lymphoma
stage II adult T-cell leukemia/lymphoma
stage III adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma
recurrent adult T-cell leukemia/lymphoma
secondary acute myeloid leukemia
de novo myelodysplastic syndromes
high risk metastatic gestational trophoblastic tumor
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
primary central nervous system non-Hodgkin lymphoma
neutropenia
infection
prolymphocytic leukemia
AIDS-related peripheral/systemic lymphoma
AIDS-related primary CNS lymphoma
primary systemic amyloidosis
intraocular lymphoma
stage I mantle cell lymphoma
contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
contiguous stage II grade 3 follicular lymphoma
contiguous stage II adult diffuse small cleaved cell lymphoma
contiguous stage II mantle cell lymphoma
contiguous stage II adult diffuse mixed cell lymphoma
contiguous stage II adult immunoblastic large cell lymphoma
contiguous stage II adult diffuse large cell lymphoma
contiguous stage II adult Burkitt lymphoma
contiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II mantle cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
recurrent mantle cell lymphoma
angioimmunoblastic T-cell lymphoma
anaplastic large cell lymphoma
stage I mycosis fungoides/Sezary syndrome
stage II mycosis fungoides/Sezary syndrome
stage III mycosis fungoides/Sezary syndrome
stage IV mycosis fungoides/Sezary syndrome
recurrent mycosis fungoides/Sezary syndrome
noncontiguous stage II small lymphocytic lymphoma
noncontiguous stage II marginal zone lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
stage I marginal zone lymphoma
stage I small lymphocytic lymphoma
stage III small lymphocytic lymphoma
stage III marginal zone lymphoma
stage IV small lymphocytic lymphoma
stage IV marginal zone lymphoma
contiguous stage II marginal zone lymphoma
contiguous stage II small lymphocytic lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
childhood myelodysplastic syndromes
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-09-04
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: SUPPORTIVE_CARE

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.

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 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Kent Sepkowitz, MD
role: STUDY_CHAIR
References:
citation: 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. doi: 10.1056/NEJMoa040446.