Clinical trial NCT00110045: Caspofungin Acetate in Treating Aspergillosis in Patients With Hematologic Cancer or in Patients Who Have Undergone a Stem Cell Transplant
Official title: A Multicenter, Open, Phase II Study to Estimate the Activity and Safety of Caspofungin (CASP) in the First-Line Treatment of Probable and Proven Invasive Aspergillosis (IA) in Patients With Hematological Malignancies (HM) or Recipients of Autologous Haematopoietic Stem Cell Transplantation and Those With Allogeneic Haematopoietic Stem Cell Transplantation (HSCT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cancer
Keywords: infection
ataxia-telangiectasia
accelerated phase chronic myelogenous leukemia
acute undifferentiated leukemia
blastic phase chronic myelogenous leukemia
meningeal chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
chronic eosinophilic leukemia
primary myelofibrosis
chronic neutrophilic leukemia
essential thrombocythemia
polycythemia vera
adult acute lymphoblastic leukemia in remission
recurrent adult acute lymphoblastic leukemia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myeloid leukemia in remission
recurrent adult T-cell leukemia/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
refractory chronic lymphocytic leukemia
stage 0 chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
progressive hairy cell leukemia, initial treatment
refractory hairy cell leukemia
prolymphocytic leukemia
recurrent adult Hodgkin lymphoma
stage I adult Hodgkin lymphoma
stage II adult Hodgkin lymphoma
stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
recurrent mycosis fungoides/Sezary syndrome
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 cutaneous T-cell non-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
adult grade III lymphomatoid granulomatosis
recurrent adult grade III lymphomatoid granulomatosis
Waldenstrom macroglobulinemia
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
contiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult Burkitt lymphoma
stage I adult Burkitt lymphoma
stage III adult Burkitt lymphoma
stage IV adult Burkitt lymphoma
contiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
stage I adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
contiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
stage I adult diffuse mixed cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage IV adult diffuse mixed cell lymphoma
contiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
stage I adult immunoblastic large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
contiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
stage I adult lymphoblastic lymphoma
stage III adult lymphoblastic lymphoma
stage IV adult lymphoblastic lymphoma
contiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 1 follicular lymphoma
stage I grade 1 follicular lymphoma
stage III grade 1 follicular lymphoma
stage IV grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
stage I grade 2 follicular lymphoma
stage III grade 2 follicular lymphoma
stage IV grade 2 follicular lymphoma
contiguous stage II grade 3 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
stage I grade 3 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 3 follicular lymphoma
contiguous stage II mantle cell lymphoma
noncontiguous stage II mantle cell lymphoma
stage I mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
contiguous stage II marginal zone lymphoma
noncontiguous stage II marginal zone lymphoma
stage I marginal zone lymphoma
stage III marginal zone lymphoma
stage IV marginal zone lymphoma
splenic marginal zone lymphoma
contiguous stage II small lymphocytic lymphoma
noncontiguous stage II small lymphocytic lymphoma
stage I small lymphocytic lymphoma
stage III small lymphocytic lymphoma
stage IV small lymphocytic lymphoma
intraocular lymphoma
primary central nervous system non-Hodgkin lymphoma
post-transplant lymphoproliferative disorder
extramedullary plasmacytoma
isolated plasmacytoma of bone
monoclonal gammopathy of undetermined significance
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
primary systemic amyloidosis
refractory multiple myeloma
de novo myelodysplastic syndromes
myelodysplastic/myeloproliferative neoplasm, unclassifiable
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
atypical chronic myeloid leukemia, BCR-ABL1 negative
chronic myelomonocytic leukemia
disseminated neuroblastoma
high risk metastatic gestational trophoblastic tumor
recurrent neuroblastoma
recurrent ovarian epithelial cancer
stage II ovarian epithelial cancer
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
recurrent ovarian germ cell tumor
recurrent malignant testicular germ cell tumor
stage III malignant testicular germ cell tumor
secondary acute myeloid leukemia
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
chronic phase chronic myelogenous leukemia
contiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
recurrent adult acute myeloid leukemia
stage I adult diffuse small cleaved cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
T-cell large granular lymphocyte leukemia
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2005-05-04
Enrollment: 171
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: SUPPORTIVE_CARE

Brief summary: RATIONALE: Antifungals, such as caspofungin acetate, may be effective in treating fungal infections caused by chemotherapy or stem cell transplant.

PURPOSE: This phase II trial is studying how well caspofungin acetate works as first-line treatment for aspergillosis in patients with hematologic cancer or in patients who have undergone a stem cell transplant.

Detailed description: OBJECTIVES:

Primary

* Determine the activity of caspofungin acetate as first-line therapy for proven or probable invasive aspergillosis, in terms of response rate, in patients with hematologic malignancies or in patients who have undergone hematopoietic stem cell transplantation.

Secondary

* Determine the 84-day response rate in patients treated with this drug.
* Determine the 84-day survival rate in patients treated with this drug.
* Determine the safety of this drug, in terms of the rate of overall drug-related adverse events, the rate of overall drug-related serious adverse events, and the rate of drug-related adverse events leading to treatment discontinuation, in these patients.

OUTLINE: This is an open-label, multicenter study. Patients are stratified according to disease and/or type of prior hematopoietic stem cell transplantation (HSCT) (hematologic malignancy or autologous HSCT vs allogeneic HSCT).

Patients receive caspofungin acetate IV over approximately 1 hour once daily on days 1-15 in the absence of disease progression or unacceptable toxicity.

Patients achieving a complete response (CR) or partial response (PR) after day 15 may continue to receive caspofungin acetate as above until day 84 OR discontinue study treatment after day 15 and shift to an oral antifungal drug for maintenance therapy or prophylaxis, if considered to be in the best interest of the patient. Patients achieving stable disease after day 15 continue to receive caspofungin acetate as above until day 28. These patients then undergo a second evaluation. Patients who maintain stable disease continue to receive caspofungin acetate as above until day 84. Patients achieving CR or PR are treated as per CR or PR treatment described above.

After completion of study treatment, patients are followed weekly for 30 days.

PROJECTED ACCRUAL: A total of 149 patients (87 in stratum 1, 62 in stratum 2) will be accrued for this study within 18 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of proven or probable invasive aspergillosis (IA)

  * Patients with a diagnosis of possible IA are eligible provided they are upgraded to probable or proven IA by culture and/or histology results and Aspergillus galactomannan evaluation within 7 days after study entry
* Meets any of the following criteria:

  * Diagnosis of a hematologic malignancy
  * Underwent autologous or allogeneic hematopoietic stem cell transplantation

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* Karnofsky 20-100%

Life expectancy

* Not specified

Hematopoietic

* Not specified

Hepatic

* AST and ALT ≤ 5 times upper limit of normal (ULN)
* Bilirubin ≤ 5 times ULN
* Alkaline phosphatase ≤ 5 times ULN
* No severe hepatic insufficiency

  * Child-Pugh score ≤ 9

Renal

* No severe renal failure requiring hemodialysis or peritoneal dialysis
* Creatinine \< 3.4 mg/dL

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective double-method contraception
* No known HIV positivity
* No history of allergy or adverse reaction to echinocandin drugs
* No known bacterial infection that is not adequately treated
* No psychological, familial, social, or geographical condition that would preclude study participation or compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

* See Disease Characteristics

Chemotherapy

* Not specified

Endocrine therapy

* Not specified

Radiotherapy

* Not specified

Surgery

* Not specified

Other

* Prior empirical antifungal therapy allowed provided treatment duration was ≤ 72 hours
* Prior prophylactic oral antifungals allowed
* Prior prophylactic IV fluconazole allowed
* More than 14 days since prior and no concurrent investigational agents
* No prior participation in this study
* No prior echinocandins
* No other concurrent antifungal therapy

Primary outcomes:
measure: Response rate as assessed by standard criteria after completion of study treatment
Secondary outcomes:
measure: Response rate as assessed by standard and alternative criteria at 84 days and after completion of study treatment
measure: Survival rate at 84 days
measure: Safety
Other outcomes:
Locations:
city: Liege
country: Belgium
facility: CHU Liege - Domaine Universitaire du Sart Tilman
city: Creteil
country: France
facility: Centre Hospitalier Universitaire Henri Mondor
city: Lyon
country: France
facility: Hopital Edouard Herriot - Lyon
city: Paris
country: France
facility: Hopital Saint-Louis
city: Strasbourg
country: France
facility: Hopital Universitaire Hautepierre
city: Wuerzburg
country: Germany
facility: Medizinische Poliklinik, Universitaet Wuerzburg
city: Cuneo
country: Italy
facility: Ospedale Santa Croce
city: Genoa
country: Italy
facility: Istituto Nazionale per la Ricerca sul Cancro
city: Genoa
country: Italy
facility: Ospedale San Martino
city: Rome
country: Italy
facility: Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
city: Bratislava
country: Slovakia
facility: National Cancer Institute - Bratislava
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Ankara
country: Turkey
facility: Hacettepe University - Faculty of Medicine
Study officials:
affiliation: IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
name: Claudio Viscoli, MD
role: STUDY_CHAIR
References:
citation: Viscoli C, Herbrecht R, Akan H, Baila L, Sonet A, Gallamini A, Giagounidis A, Marchetti O, Martino R, Meert L, Paesmans M, Ameye L, Shivaprakash M, Ullmann AJ, Maertens J; Infectious Disease Group of the EORTC. An EORTC Phase II study of caspofungin as first-line therapy of invasive aspergillosis in haematological patients. J Antimicrob Chemother. 2009 Dec;64(6):1274-81. doi: 10.1093/jac/dkp355. Epub 2009 Oct 19.