UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Multi-centre Prospective Randomized Trial Intravenous Itraconazole versus Liposomal Amphotericin B For Empirical Antifungal Therapy In Patients With Persistent fever And Neutropenia (ILEAN study)
Title of the study (Brief title)	Intravenous Itraconazole versus Liposomal Amphotericin B For Empirical Antifungal Therapy
Region	Japan

Condition
Condition	Patients With Persistent fever And Neutropenia
Classification by specialty	Medicine in general Hematology and clinical oncology Infectious disease
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	In hematological malignancy patients with persistent fever and neutropenia, we are conducting a prospective randomized, muliti-centre trial comparing intravenous Itraconazole with liposomal amphotericin B as empirical antifungal therapy. This study aims to demonstrate noninferiority of intravenous Itraconazole compared with liposomal amphotericin B in overall favorable response.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Explanatory
Developmental phase	Phase IV

Assessment
Primary outcomes	Overall favorable response ( No.1, 2, 3, 4, and 5 key secondary outcomes all succeed)
Key secondary outcomes	1. Response of patients with base-line fungal infections by completion of trial therapy 2. No breakthrough fungal infection 3. No discontinuation due to toxicity before recovery from neutropenia 4. Resolution of fever during neutropenia 5. Survival 7 days after completion of trial therapy 6. Adverse events 7. Probable invasive fungal disease by completion of trial therapy

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Active
Stratification	YES
Dynamic allocation	YES
Institution consideration	Institution is considered as adjustment factor in dynamic allocation.
Blocking	YES
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Liposomal amphotericin B is initiated and continued at 3mg per kilogram intravenously per day.
Interventions/Control_2	Itraconazole is initiated at 200mg intravenously every12hours for 5 times followed by 200mg intravenously every 24hours.
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	15 years-old <=
Age-upper limit	79 years-old >=
Gender	Male and Female
Key inclusion criteria	1. ECOG Performance Status of 0 to 3 at initial administration of the study drug. 2. Patients who have been with chemotherapy for less than 30 days for hematological malignancy. 3. Neutropenia (an absolute neutrophil count below 500 cells per cubic millimeter ) persisted for 96 hours. 4. Patients had received more than 96 hours of systemic anti-bacterial therapy while continuing to have fever. After 96 hours, axillary temperature was above 37.5 C at least one time. 5. No prophylactic antifungal therapy without Amphotericin B syrup, micafungin, caspofungin, miconazole oral gel,and antifungal skin cream. (Patients who not received fluconazole within 4 weeks before the initial administration of the study drug) 6. Patients with adequately maintained organ functions (e.g., bone marrow, liver, heart, and kidney funtions). Platelets counts: >5,000 per cubic millimeter ALP: <3.0 times the upper limit of the institutional normal range Total bilirubin: < 3.0 times the upper limit of the institutional normal range AST (GOT): < 5.0 times the upper limit of the institutional normal range ALT (GPT): < 5.0 times the upper limit of the institutional normal range Left ventricular ejection fraction:> 50% Creatinine clearance: >30mL / min 7. Patients capable of personally giving voluntary informed consent in writing to participate in the study.
Key exclusion criteria	1. Patients have been proved invasive fungal disease at initial administration of the study drug 2. Patients have been diagnosed as definite virus or bacterial infection at initial administration of the study drug 3. Patients with prior severe allergies to intravenous itraconazole and liposomal amphotericin B 4. Patients with liver cirrhosis 5. Patients with serious, active heart disease 6. Patients with, or confirmed in the past to have had, angina pectoris, cardiac infarction, congestive heart failure 7. Patients with serious psychological disease 8. Patients who are pregnant or lactating 9. Patients who received pimozide, blonanserin, triazolam, quinidine sulfate, bepridil hydrochloride hydrate, azelnidipine, nisoldipine, simvastatin, ergotamine tartrate, dihydroergotamine mesilate, vardenafil hydrochloride hydrate, sildenafil citrate, eplerenone, aliskiren fumarate, tadalafil, or rivaroxaban 10. Patients who receive donor leukocyte infusion 11. Patients otherwise judged by investigator or sub investigator to be unsuitable 12. Patients who received other investigational products or unapproved medication or Japan clinical oncology group protocol study 13. Patients who are currently receiving or going to receive Vincristine 14. Patients who have proved invasive fungal disease in the past
Target sample size	850

Research contact person
Name of lead principal investigator	Isao Yoshida
Organization	National Hospital Organization, Shikoku Cancer Center
Division name	Hematologic oncology
Address	160 Kou, Minamiumemotocho, Matsuyama, Ehime, Japan
TEL	+81-89-999-1111
Email

Public contact
Name of contact person	Isao Yoshida
Organization	National Hospital Organization, Shikoku Cancer Center
Division name	Hematologic oncology
Address	160 Kou, Minamiumemotocho, Matsuyama, Ehime, Japan
TEL	+81-89-999-1111
Homepage URL	https://center6.umin.ac.jp/islet/ilean/
Email	iyoshida@shikoku-cc.go.jp

Sponsor
Institute	National Hospital Organization
Institute
Department

Funding Source
Organization	National Hospital Organization
Organization
Division
Category of Funding Organization
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions

Institutions

国立病院機構　北海道がんセンター（北海道）、国立病院機構　仙台医療センター（宮城県）、国立病院機構　水戸医療センター（茨城県）、国立病院機構　西群馬病院（群馬県）、国立病院機構　東京医療センター（東京都）、国立病院機構　災害医療センター（東京都）、国立病院機構　まつもと医療センター（長野県）、国立病院機構　名古屋医療センター(愛知県)、国立病院機構　金沢医療センター（石川県）、国立病院機構　福井病院（福井県）、国立病院機構　あわら病院（福井県）、国立病院機構　京都医療センター（京都府）、国立病院機構　大阪医療センター（大阪府）、国立病院機構大阪南医療センター（大阪府）、国立病院機構　姫路医療センター（兵庫県）、国立病院機構　米子医療センター（鳥取県）、国立病院機構　岡山医療センター（岡山県）、国立病院機構　南岡山医療センター（岡山県）、国立病院機構　呉医療センター（広島県）、国立病院機構　広島西医療センター（広島県）、国立病院機構　四国がんセンター（愛媛県）、国立病院機構　九州医療センター（福岡県）、国立病院機構　九州がんセンター（福岡県）、国立病院機構　長崎医療センター（長崎県）、国立病院機構　熊本医療センター（熊本県）、国立病院機構　鹿児島医療センター（鹿児島県）

Other administrative information
Date of disclosure of the study information	2011 Year 04 Month 29 Day

Progress
Recruitment status	Main results already published
Date of protocol fixation	2011 Year 01 Month 30 Day
Anticipated trial start date	2011 Year 05 Month 01 Day
Last follow-up date	2015 Year 03 Month 31 Day
Date of closure to data entry	2015 Year 07 Month 14 Day
Date trial data considered complete	2015 Year 07 Month 14 Day
Date analysis concluded	2015 Year 07 Month 14 Day

Related information
URL releasing protocol
Publication of results	Published
URL releasing results	http://learningcenter.ehaweb.org/eha/2016/21st/133365/isao.yoshida.multicenter.prospective.randomize
Results
Other related information	21th Congress of European Hematology Association

Management information
Registered date	2011 Year 04 Month 29 Day
Last modified on	2017 Year 05 Month 22 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000006558