UMIN-CTR Clinical Trial

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

aplastic anemia

Classification by specialty

Hematology and clinical oncology

Classification by malignancy

Others

Genomic information

YES

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

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.

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

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

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

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

Institute

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

Institute

Department

Personal name

Organization

None

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

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

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2017

Year

12

Month

18

Day

URL releasing protocol

Publication of results

Unpublished

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

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 related information

Registered date

2017

Year

12

Month

18

Day

Last modified on

2022

Year

06

Month

22

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034771