W-JHS AA02

JRCT ID: jRCTs071190032

Registered date:21/10/2019

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: aplastic anemia
• Date of first enrollment: 26/11/2019
• Target sample size: 60
• Study type: Interventional

Intervention(s)

1. The administration of rATG; 2.5 mg/kg, iv. daily, day 1 - day 5 + CsA; 5 mg/kg, po. bid (before breakfast and before dinner) +adrenalcorticosteroid (the dose is mentioned after) is started. CsA used is Neoral or generic drug emulsified in the same way with Neoral. A blood level of CsA is measured and the dose which CsA blood level 2 hours after oral administration (C2) reachs 600 - 900 ng/mL is adjusted. The investigator shall reduce the dose of CsA by 25% on this occasion when blood trough level (C0) just before the administration is beyond 250 ng/mL because renal function disorder may occur (2). When serum creatinine level also becomes higher than 150% of baselines, the 25% dose reduction of CsA shall be performed. If C2 did not reach to 600 ng/mL, then dose of CsA is appropriately increased.
2. EPAG; 75 mg, po. daily (before sleep, requires to pass more than at least 2 hours after dinner) is started from day 6.
3. The dose of steroid is as follows:
Day 1 - day 5: methylprednisolone 2 mg/kg/day
Day 6: Methylprednisolone 1 mg/kg/day
Day 8, 10, 12, 14, 16, 18, 20: prednisolone 0.5 mg/kg/day
Discontinuation after day 21
4. The administration of CsA and EPAG is continued for 26 weeks. When it passed 26 weeks, further treatment mentioned above is entrusted to the investigator in each medical institution after 27 weeks if patients reached Camitta criteria CR or PR. However, the administration is continued for 52 weeks even if the dose of CsA is reduced. The treatment after 53 weeks is not specified. If patients did not reach CR or PR at 26 weeks, treatment after 27 weeks is entrusted to the investigator in each medical institution (it is not specified in this study).

Outcome(s)

• Primary Outcome: CR or PR achievement rate at week 12 after protocol treatment (hematological response rate by Camitta criteria)

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 after protocol treatment
4.Correlation between hematological response rate at week 2, 4, 8, 12 and 26 after protocol treatment, and rATG blood level and the following markers: PNH-type blood cells, HLA class I allele-lacking cells, plasma thrombopoietin levels
5.Hematological response rate at week 52 after protocol treatment and treatment contents at each time point
6.Response duration and recurrence rate in patients with hematological 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 >= grade 3 adverse events, 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 point of the signature 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 non-severe or sever aplastic anemia who meet the following both A and B.
A) Meet the following 2 or more and requires or estimated to require periodical transfusion
a) neutrophil count < 1,000/mm3
b) platelet count < 50,000/ mm3
c) reticulocyte count < 60,000/ mm3
B) 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 rATG, CsA, EPAG, anabolic steroid and allogeneic hematopoietic stem cell transplantation.
2) Fulminant form characterized by the neutrophil count of 0/mm3 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 grade 2 or more hepatic disorder, cardiac disorder, or renal dysfunction according to CTCAE v5.0
10)Any other Patients who were judged to have difficulty participating in this study by investigators.

Related Information

• Primary Sponsor: Ishiyama Ken
• Source(s) of Monetary Support: Novartis Pharma K.K.