UMIN-CTR Clinical Trial

Basic information
Public title	Efficacy of cyclosporine therapy in the treatment of non-severe aplastic anemia
Acronym	Aplastic anemia 01 study in West Japan Hematology Study Group (W-JHS AA01 study)
Scientific Title	Efficacy of cyclosporine therapy in the treatment of non-severe aplastic anemia
Scientific Title:Acronym	Aplastic anemia 01 study in West Japan Hematology Study Group (W-JHS AA01 study)
Region	Japan

Condition
Condition	aplastic anemia
Classification by specialty	Hematology and clinical oncology
Classification by malignancy	Others
Genomic information	YES

Objectives
Narrative objectives1	We prospectively determine the efficacy of cyclosporine (CsA) in the treatment of non-severe aplastic anemia which does not require blood transfusions.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Hematologic improvement in the erythrocyte (HI-E) and platelet (HI-P) count according to IWG response criteria 2006 at 8 weeks after CsA therapy.
Key secondary outcomes	1.Increment of reticulocyte >=20,000/mm3 at 8 weeks after the initiation of CsA. 2.HI-E or HI-P at 4 weeks, 16 weeks and 52 weeks after the initiation of CsA. 3.Increment of reticulocyte >=20,000/mm3 at 4 weeks, 16 weeks and 52 weeks after the initiation of CsA. 4.Correlation between HI-E or HI-P at 8 weeks after the initiation of CsA and the following biomarkers; presence of increased PNH-type cells, presence of cells with HLA class I allele-lacking leukocytes, and plasma thrombopoietin. 5.Correlation between HI-E or HI-P at 8 weeks after the initiation of CsA and somatic gene mutations. 6.Time to HI-E or HI-P after the initiation of CsA. 7.Incidence of somatic mutations in granulocyts. 8.Adverse events >=grade 3 associated with CsA therapy.

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	1. Start CsA (Neoral or generic drugs emulsified in the same way as Neoral) at a dose of 3.5 mg/kg, bid (before breakfast and before dinner). 2. Measure the blood concentration of cyclosporine at 2 hours (C2) after taking the drug and determine the minimum dose of cyclosporine that produces C2 >600 ng/mL. Continue the dose of cyclosporine for 8 weeks. 3. Continue the treatment for further 44 weeks (a total of 52 weeks) when patients meet the response criteria of HI-E or HI-P at the end of the 8 week treatment. Treatments after the 52 weeks are not specified. When patients do not meet the IWG response criteria 2006 at the end of 8 weeks, the treatment is terminated and treatments after 9 weeks are not specified.
Interventions/Control_2
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	16 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1) Aged >=16 years. 2) Good PS (0, 1 and 2) 3) Meet the diagnostic criteria of aplastic anemia of stage 1 or 2, and is planned to receive CsA as a first treatment. 4) Meet both of the platelet count < 100,000/mm3 and the reticulocyte count < 60,000/ mm3, and at least one of the followings; hemoglobin level <10.0 g/dL and the neutrophil count < 1,500/ mm3. 5) The percentage of cellular component in a bone marrow biopsy specimen is <30%. 6) No treatment history with anti-thymocyte globulin (ATG), CsA, anabolic steroid, erythropoietin preparation, eltrombopag and vitamin K. 7) Not pregnant, or agree to contraception during the study period.
Key exclusion criteria	1) Disease duration >=5 years. Patients whose disease onset is unclear are not excluded. 2) Severe (stage 3 or 4) or moderately severe (stage 3) aplastic anemia that is defined by the severity criteria by the Ministry of Health, Welfare, and Labor of Japan. 3) Patients with chromosomal abnormalities related to MDS that were defined by WHO 2008 diagnostic criteria. 4) Patients showing dysplastic signs defined as category A morphological abnormalities (1. hypo-segmented mature neutrophils (pseudo-Pelger nuclear abnormality), 2. degranulation of neutrophils, 3. micromegakaryocytes, 4. ringed sideroblasts) in "Atlas on diagnosis accuracy division and morphological diagnosis based on morphologic dysplasia of refractory anemia (myelodysplastic syndromes) ". 5) Congenital aplastic anemia including Fanconi anemia. 6) Patients who developed a cancer or received chemotherapy or radiotherapy within 5 years of entry. 7) Patients with uncontrollable infections. 8) Patients with severe impairment of the liver, heart or kidney (eGFR < 45 mL/min/1.73m2). 9) Patients who were judged to be ineligible for the study participation by investigators.
Target sample size	33

Research contact person
Name of lead principal investigator	1st name Shinji Middle name Last name Nakao
Organization	Kanazawa University Hospital
Division name	Department of Hematology
Zip code	920-8641
Address	13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan
TEL	076-265-2000(ext2273)
Email	snakao8205@staff.kanazawa-u.ac.jp

Public contact
Name of contact person	1st name Ken Middle name Last name Ishiyama
Organization	Kanazawa University Hospital
Division name	Department of Hematology
Zip code	920-8641
Address	13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan
TEL	076-265-2000(ext2273)
Homepage URL
Email	ishiyama-knz@umin.ac.jp

Sponsor
Institute	Cooperative study between the West Japan Hematology Study Group and Clinical Research Support Center Kyushu
Institute
Department

Funding Source
Organization	None
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

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

IRB Contact (For public release)
Organization	Kanazawa University Hospital
Address	13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan
Tel	076-265-2049
Email	crc.irb-knz@esct.jp

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

Other administrative information
Date of disclosure of the study information	2017 Year 12 Month 18 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled	34
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	No longer recruiting
Date of protocol fixation	2017 Year 12 Month 14 Day
Date of IRB	2017 Year 12 Month 19 Day
Anticipated trial start date	2017 Year 12 Month 20 Day
Last follow-up date	2021 Year 06 Month 30 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2017 Year 12 Month 18 Day
Last modified on	2022 Year 06 Month 22 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000034771