This prospective, open-label, nonrandomized, multicenter clinical trial aims at comparing the efficacy and safety of combined use of TPO-RAs with low-dose anti-CD20 monoclonal antibody vs. the best available therapy(BAT)in adult immune thrombocytopenia with autoantibodies failed (due to intolerance or resistance) to first-line treatment.
This is a prospective, open-label, nonrandomized, multicenter clinical trial aiming at comparing the efficacy and safety of combined use of TPO-RAs with low-dose anti-CD20 monoclonal antibody vs. the best available therapy(BAT)in adult immune thrombocytopenia (ITP) with autoantibodies failed (due to intolerance or resistance) to first-line treatment. The subjects include ITP secondary to connective tissue diseases (including but not limited to systemic lupus erythematosus, Sjogren's syndrome and rheumatoid arthritis), primary ITP with positive antinuclear antibody but not up to the diagnostic criteria of connective tissue diseases, primary Evans syndrome, Evans syndrome secondary to connective tissue diseases, and primary ITP with positive Coomb's test but not up to the diagnostic criteria of Evans syndrome. Adult ITP patients with autoantibodies (18-65 years) will be nonrandomly divided into the following two treatment groups: 1. combined use of TPO-RAs with low-dose anti-CD20 monoclonal antibody. 2. the best available therapy(BAT)other than combined use of TPO-RAs with low-dose anti-CD20 monoclonal antibody. The current treatment strategies and possible risks of combined use of TPO-RAs with low-dose anti-CD20 monoclonal antibody in the treatment of ITP with autoantibodies will be fully introduced to the patients by the researchers. Then the patients will be divided into one of the two groups according to the patients' will.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
94
Experimental: Combined use of TPO-RAs with low-dose anti-CD20 antibody The starting dose of eltrombopag is 50-75mg once daily. The starting dose of hetrombopag is 5.0-7.5mg once daily. The starting dose of avatrombopag is 20-40mg once daily. Prior to or within 2 weeks after initiation of TPO-RAs therapy, a single dose of Rituximab at 375mg/m2 or divided doses of Rituximab at 100mg once a week for 2-4 weeks, or a single dose of ortuzumab at 1000mg can be administered.. The dosage will be adjusted according to the results of laboratory examinations and patient tolerance.
The best available therapy except for combined use of TPO-RAs with low-dose anti-CD20 antibody includes but not limited to glucocorticoids, intravenous immunoglobulin, recombinant human thrombopoietin, TPO receptor agonists monotherapy, rituximab monotherapy, immunosuppressants, etc., and the researchers will adjust the treatment plan at any time according to the patient's condition.
Institute of Hematology & Blood Diseases Hospital
Tianjin, Tianjin Municipality, China
RECRUITINGPlatelet response
At weeks 4-24, the proportion of subjects with platelet count (PLT) ≥30×10\^9/L and at least 2 times the baseline value in 4 out of 6 consecutive tests (at least 1 week interval between each test).
Time frame: From the start of study treatment (Day 1) up to the end of week 24
Platelet response
Proportion of subjects who achieve response (R) within 4, 8 and 12 weeks of treatment.
Time frame: From the start of study treatment (Day 1) up to the end of week 4, 8 and 12
Platelet response
Proportion of subjects who achieve complete response (CR) within 4, 8 and 12 weeks of treatment.
Time frame: From the start of study treatment (Day 1) up to the end of week 4, 8 and 12
Time to platelet response
Time to response is defined as time from the start of treatment to the first time of achieving a platelet count ≥ 30×10\^9/ L and at least doubling of the baseline count during the whole 24 weeks.
Time frame: From the start of study treatment (Day 1) up to the end of week 24
Duration of platelet response
Total duration of time a participant with a response of R.
Time frame: From the start of study treatment (Day 1) up to the end of week 24
Bleeding score
The incidence and grade of bleeding symptoms according to the World Health Organization Bleeding Scale.
Time frame: From the start of study treatment (Day 1) up to the end of week 24
ITP-Patient Assessment Questionnaire
In all participants, ITP-Patient Assessment Questionnaire will be used to assess the health related quality of life before and after treatment.
Time frame: From the start of study treatment (Day 1) up to the end of week 24
Changes of disease activity index in patients with systemic lupus erythematosus
The proportion of subjects with improvement of disease activity index in patients with systemic lupus erythematosus according to the SLEDAI standard.
Time frame: From the start of study treatment (Day 1) up to the end of week 24
The improvement of symptoms
The proportion of subjects with improvement of symptoms including skin symptom, joint pain, dry mouth and dry eyes.
Time frame: From the start of study treatment (Day 1) up to the end of week 24
Improvement in immune indexes
The proportion of subjects with improvement immune indexes including antinuclear antibody, extractable nuclear antigens spectrum and Coomb's test.
Time frame: From the start of study treatment (Day 1) up to the end of week 24
Discontinuation rate of glucocorticoids
The proportion of subjects with discontinuation use of glucocorticoids.
Time frame: From the start of study treatment (Day 1) up to the end of week 24
Hemoglobin response
The proportion of subjects with Evans syndrome who have a hemoglobin level \> 110g/L (female) or \> 120g/L (male) in the absence of any recent transfusion and without ongoing hemolysis for 2 consecutive weeks (at least 1 week interval).
Time frame: From the start of study treatment (Day 1) up to the end of week 24
Hemoglobin response
The proportion of subjects with Evans syndrome who have a hemoglobin level\> 100g/L with at least a 20g/L increase from the pretreatment level for 2 consecutive weeks (at least 1 week interval).
Time frame: From the start of study treatment (Day 1) up to the end of week 24
functional assessment of chronic illness therapy-fatigue
In all participants, functional assessment of chronic illness therapy-fatigue questionnaire will be used to assess the health related quality of life before and after treatment.
Time frame: From the start of study treatment (Day 1) up to the end of week 24
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