A Multicenter, Prospective, Randomized Controlled Study Comparing Glucocorticoid Combined With Sirolimus With Monotherapy of Glucocorticoid in the Treatment of Newly Diagnosed Mild Autoimmune Hemolytic Anemia

Overview

This study is a prospective, multicenter, randomized controlled trial. A total of 216 adult patients with newly diagnosed wAIHA were planned to be included and randomly assigned in a 1:1 ratio to the experimental group (glucocorticoid combined with sirolimus) or the control group (glucocorticoid monotherapy). The initial dose of sirolimus in the experimental group was 1mg/d, adjusted according to the blood drug concentration. The target concentration was 4-12ng/mL, and the treatment course was 6 months. Both groups of hormones were gradually reduced according to the standard protocol. All patients were followed up for 24 months, and the differences between the two groups at endpoints such as the hormone-free sustained response rate at the 12th month were compared.

Detailed description

This study was a randomized controlled study. Two groups of patients were randomly assigned in a 1:1 ratio to receive the following treatment regimens:

1. Glucocorticoid monotherapy group Prednisone at a dose of 1-2 mg/kg/d (or an equivalent dose of methylprednisolone) is taken orally for 2-3 weeks, and then the dosage is reduced regularly. The total course of treatment is approximately 3-6 months. The reduction plan was formulated by the researchers based on clinical practice. 2. Glucocorticoid combined with sirolimus group Glucocorticoids: The usage, dosage and reduction regimen are the same as those in the monotherapy group. \| Sirolimus: Starting dose 1 mg/d, orally, once a day. After reaching a steady state 7 to 14 days of medication, monitor the trough concentration. The target trough concentration range is 4 to 12 ng/mL. Adjust the dosage based on the results of blood drug concentration monitoring. The total course of treatment for sirolimus is 6 months. If grade ≥3 related adverse events or trough concentration \&gt occur; 12 ng/mL. Consider reducing the dosage or suspending the administration

Interventions

• Drug Glucocorticoids
  Glucocorticoids combined with sirolimus

Primary outcome measures

• The 12-month sustained remission rate [Time frame: 12 months]

Secondary outcome measures (1)

• Safety [Time frame: 1，3，6，12 months]

Eligibility criteria

Inclusion criteria

• Age ≥18 years old, gender not limited;
• Diagnosed as newly diagnosed wAIHA and requiring systemic immunosuppressive therapy (those with short-term hormone exposure of ≤2 weeks before enrollment can be included)
• After a comprehensive rheumatology and immunology assessment, there is no evidence of clinical organ involvement in SLE or other connective tissue diseases (only serological abnormalities can be included).
• Positive Coombs test (IgG type, IgG+C3d type, or only C3d type with a condensed agglutinin titer of 1:64);
• Active hemolytic anemia, hemoglobin (HGB) ≤ 100 g/L;
• Liver and kidney function: Alanine aminotransferase (ALT) < 3 times the upper limit of the normal value (ULN), isolated elevation of aspartate aminotransferase (AST) (normal ALT) is acceptable; Serum creatinine ≤2×ULN;
• Eastern Cooperative Oncology Group (ECOG) Performance status score ≤2 points;
• Those with a history of malignant tumors must meet the following conditions:

Radical treatment has been achieved; The disease-free survival period complies with the protocol provisions (such as ≥1 year for basal cell carcinoma, ≥5 years for early solid tumors, ≥5 years for curable lymphoma, etc.); There is currently no evidence of recurrence. Those who do not meet the above conditions (such as CLL, advanced solid tumors, and active tumors) are not included.

• Voluntarily sign a written informed consent form.

Exclusion criteria

• Pregnant or lactating patients;
• Clinically confirmed SLE or other definite connective tissue diseases;
• Secondary AIHA secondary to lymphoproliferative diseases, other hematological malignancies, solid tumors, infections, and drugs;
• Cold-resistant type or hybrid type AIHA;
• Received before group enrollment:

Other immunosuppressants (such as rituximab, cyclosporine, etc., regardless of the duration); Glucocorticoid treatment for more than 2 weeks;

• Severe cardiac insufficiency (NYHA grade III/IV, or LVEF < 40%);
• Currently active malignant tumors, or previous tumors that do not meet the requirements of Article 8 of the inclusion criteria;
• Chronic active infections (active tuberculosis, active hepatitis B/C, etc.);
• Severe immunodeficiency diseases, HIV infection (CD4⁺ < 200/μL), currently using other potent immunosuppressants, and using targeted biological agents within the last 3 months;
• Have a history of severe allergy to sirolimus, glucocorticoids or related excipients;
• Other circumstances where the researcher deems it inappropriate to participate.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Peking union medical college hospital — Beijing

Publications

• 1.Birgens H, Frederiksen H, Hasselbalch HC, et al. A phase III randomized trial comparing glucocorticoid monotherapy versus glucocorticoid and rituximab in patients with autoimmune haemolytic anaemia. Br J Haematol. 2013;163(2):244-252.https://doi.org/10.1111/bjh.12541. 2.Kuter DJ. Warm autoimmune hemolytic anemia and the best treatment strategies. Hematology Am Soc Hematol Educ Program. 2022;2022

Identifiers

NCT: NCT07518277 · GC vs. GC+Sirolimus

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗