A study of silorimus for pure red cell aplasia

JRCT ID: jRCTs031230310

Registered date:28/08/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: acquired chronic pure red cell aplasia
• Date of first enrollment: 28/08/2023
• Target sample size: 5
• Study type: Interventional
• Intervention(s): Sirolimus dose is started at 2 mg orally once daily after breakfast and monitored by scheduled trough whole blood concentrations, and if the concentration is 15 ng/mL or higher, the dose is reduced from 2 mg to 1 mg daily. do. If less than 5 ng/mL, increase to 3 mg daily. Thereafter, the dose should be increased until the target trough concentration is within the range of 5-15 ng/mL, but the maximum dose should be 4 mg once daily.

Outcome(s)

Primary Outcome

Change in hemoglobin (Hb) levels from baseline (week 0) to week 24 or discontinuation.
However, the hemoglobin (Hb) level should be measured at least 14 days after the last red blood cell transfusion.

Secondary Outcome

1) Hemoglobin (Hb) level: change from baseline (week 0) at 12 weeks, 36 weeks, 48 weeks, and 52 weeks after starting study drug
However, the hemoglobin (Hb) level should be measured at least 14 days after the last red blood cell transfusion.
2) Reticulocyte count: change from baseline (week 0) at 12, 36, 48, and 52 weeks after starting study drug
3) Red blood cell transfusion volume from the end of the sirolimus dose adjustment period (12 weeks) to the end of the observation period (52 weeks)
4) Response rate: Percentage of cases with an increase in hemoglobin level of 2.0 g/dL or more at 24 and 48 weeks after starting treatment
5) Changes in hemoglobin (Hb) levels (at the start, 12 weeks, 24 weeks, 36 weeks, 48 weeks, 52 weeks)
6) Change in reticulocyte count (at the start, 12 weeks, 24 weeks, 36 weeks, 48 weeks, 52 weeks)
7) Changes in MCV (initial, 12 weeks, 24 weeks, 36 weeks, 48 weeks, 52 weeks)
8) Change in red blood cell transfusion volume from baseline (week 0) to week 52
9) Whole blood trough concentration
10) FACIT-Fatigue Scale

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Inclusion criteria:
(1) Common criteria of acquired chronic pure red cell aplasia (PRCA): the diagnosis referred to a clinical guide for PRCA by a Japanese National Research Group on Idiopathic Bone Marrow Filure Syndromes of the Ministry of Health, Labour, and Welfare, revised in 2021.
(2) Hemoglobin (Hb) level of less than 9 g/dL within 4 weeks before informed consent
(3) At least one of the indications listed below (a) to (d):
(a) a refractory disease: anemia being refractory to cyclosporine (CsA) treatment with a full dose for preceding >= months
(b) an intolerant disease: having CsA treatment being withdrawn due to its adverse events (ex. renal toxicity, hypertension)
(c) an intoerant disease: withholding CsA treatment due to its adverse events (ex. renal toxicity, hypertension)
(d) a relapsed disease: anemia being relapsing due to dose reduction or cesation of CsA treatment after clinical response to CsA
(4) Age 18 years or above
(5) Written informed consent

Exclude criteria

Exclusion criterias:
(1) A woman during pregnancy or breastfeeding, or a man or woman without consent to contraception until 12 weeks after last dose of administration of the study drug
(2) Clinical symptoms of interstitial lung disease such as cough, dyspnea, or fever
(3) A medical history of sirolimus or other mTOR inhibitors
(4) A medical history of immunosuppressive therapy (cyclosporine, corticosteroid, cyclophosphamide, etc.) for acquired chronic pure red cell aplasia within 5 weeks before consent.
(5) A major surgery, requiring red blood cell transfusion, such as a surgery of a body cavity or a surgery with 3 or more sutures (including, biopsy), being scheduled between 2 weeks prior to the first dose of the study drug and 1 year after the consent
(6) A hematopoietic stem cell transplantation scheduled within 6 months of the consent
(7) Any of the laboratory results within 4 weeks of the consent; platelet count < 75,000/mm3, neutrophil count < 1,000/mm3, of white blood cell count < 2,500/mm3
(8) AST or ALT > 3 times the upper limit of the reference range within 4 weeks of the consent
(9) Child-Pugh C
(10) A history of allergic reactions to sirolimus or additives in the test drug
(11) Immunodeficiet state such as HIV infection or primary immunodeficiency syndrome
(12) Any of the following; a-d
a) HBs Ag positive
b) HBV-DNA positive WHEN either HBs Ab or HBc Ab positive
c) With active hepatits with HCV infection (EXCEPT HCV Ab positive with normal liver enzymes)
d) A history of infection or suspected infection of Mycobacterium tuberculosis (QFT/T-SPOT positive)
(13) A history of cancer within 2 years of consent
(14) A medical history of thymoma treatment
(15) Active infections
(16) A history of intoxication of illicit drug or alcohol within 5 years, or a history of abuse of illicit drug or alcohol within 1 year before consent
(17) A history of participation in other clinical trials or clinical studies within 30 days before the consent AND having taken investigational drugs or having used investigational devices
(18) Those deemed to be unsuitable by the primary investigator

Related Information

• Primary Sponsor: Nakazawa Hideyuki
• Source(s) of Monetary Support: Norbel Pharma Co.,Japanese Society of Hematology, Kantokoshinetsu Office