W-JHS AA03

JRCT ID: jRCTs071240082

Registered date:06/12/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: aplastic anemia
• Date of first enrollment: 06/12/2024
• Target sample size: 30
• Study type: Interventional

Intervention(s)

1. hATG 40 mg/kg/day x 4 days + CsA 5 mg/kg/min2 (before breakfast and dinner) + corticosteroids (dosage to be discussed later). The blood concentration of CsA should be measured and the dosage adjusted so that the blood concentration (C2) level at 2 hours after oral administration is at least 600 ng/mL. If the blood trough concentration (C0) immediately before oral administration exceeds 250 ng/mL, renal dysfunction may occur, so the CsA dose should be reduced by 25%. The CsA dose should also be reduced by 25% if the serum creatinine level is greater than 150% of baseline; if C2 is less than 600 ng/mL, the CsA dose should be increased accordingly.
2. Beginning on the first day of treatment, ROMI is injected subcutaneously once a week; the starting dose of ROMI is 10 ug/kg, and the dose is fixed for the first 4 weeks. If CR is met for 4 consecutive weeks after Week 14, the dose is maintained and changed to once every 2 weeks. If the patient continues to meet CR criteria and there are no safety issues, the once-per-twice-week dosing interval should be maintained in the same manner. If the platelet count, hemoglobin concentration (Hb), or neutrophil count fails to meet the criteria for CR after the once-per-two-week interval, the dosing interval is changed from once every two weeks to once a week.
3. The dose of steroid is as follows:
Day 1 - day 4: methylprednisolone 2 mg /kg /day
Day 5: Methylprednisolone 1 mg /kg /day
Day 7, 9, 11, 13, 15, 17, 19: prednisolone 0.5 mg /kg /day
Discontinuation after day 21
Increased doses for serodiagnosis treatment are allowed.
4.The dosage of CsA and ROMI after 27 weeks is left to the discretion of the medical institution. However, CsA should be continued for at least 52 weeks, even if the dose is reduced.
The continuation of protocol treatment after Week 27 for patients who have not reached CR or PR at Week 26 is left to the discretion of each medical institution.

Outcome(s)

• Primary Outcome: CR or PR achievement rate at week 12 after protocol treatment (hematolog ical response rate by NIH criteria partially revised)

Secondary Outcome

1.Type and frequency of chromosomal abnormalities detected at protocol treatment initiation
2.Type and frequency of somatic gene mutations detected at protocol treatment initiation
3.Hematological response rate at week 26, 52 after protocol treatment
4.Correlation between hematological response rate at week 12, 26 and 52 after protocol treatm
ent and the following markers: PNH-type blood cells, HLA class I allele-lacking cells, plasma thrombopoietin levels
5.Response duration and recurrence rate in patients with hematological response
6.Time to response in patients with hematologic response
7.Appearance of chromosomal abnormalities at week 26 and 52 after protocol treatment or increase in chromosomal abnormalities detected by then
8.Appearance of somatic mutated clone at week 12, 26 and 52 after protocol treatment or increase in mutated clone detected by then
9.Frequency of >= g rade 3 adverse events (only causally related), serious adverse events and death associated with the protocol treatment

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: < 80age old
• Gender: Both

Include criteria

1) Aged >=18 years and <80 years (at time pointof the sig nature of ICF).
2) Patients who understand the informed consent and can sign the informed consent form by his/her free will.
3) Patients who obey the protocol visit and other rules.
4) Good PS (0, 1 and 2)
5) Patients with sever aplastic anemia who meet the percentage of cellular component in a bone marrow biopsy specimen is <25% and no fibrosis and no hematological malignancies.
6) Not pregnant woman
7) Agree to contraception during the study period.

Exclude criteria

1) Treatment history of hATG, rATG, CsA, EPAG, anabolic steroid and allogeneic hematopoietic stem cell transplantation.
2) Fulminant form characterized by the neutrophil count of 0/uL at enrollment and that no response to G-CSF treatment for more than or equal to 1 week.
3) Patients with chromosomal abnormalities related to MDS that were defined by WHO 2008 diagnostic. Patients with del (13q) alone and -Y alone positive are eligible.
4) Patients with >= 10% of dysplasia in >= 1 series of category A and B defined in Classification of dysplasia edited by Working Group for preparation of morphologic diagnostic criteria of refractory anemia (myelodysplastic syndromes)
5) Congenital aplastic anemia including Fanconi anemia.
6) Patients who received chemotherapy or radiotherapy or patients who developed a cancer within 5 years of entry.
7) Patients with uncontrollable infections or diabetes mellitus.
8) HBs antigen positive or HBV DNA positive.
9) Patients with hepatic, cardiac, or renal dysfunction requiring treatment.
10) Patients who are judged by their physician to be unable to participate in this study.

Related Information

• Primary Sponsor: Yamazaki Hirohito
• Source(s) of Monetary Support: Kyowa Kirin Co.,Ltd.