Clinical trial NCT04915482: TPO-RAs Combined With Anti-CD20 Antibody in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies
Official title: Efficacy and Safety of TPO-RAs Combined With Anti-CD20 Antibody in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies Failed to First-line Treatment: a Prospective, Open-label, Nonrandomized, Multicenter Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Immune Thrombocytopenia (ITP)
Autoantibodies
Evan Syndrome
Connective Tissue Diseases
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
First posted: 2021-06-07
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* The patients have provided written informed consent prior to enrollment.
* 18-65 years old.
* Diagnosed as 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.
* Platelet count\<30 ×10\^9/L at screening.
* Patients who have received at least one first-line treatment of ITP (glucocorticoid and / or intravenous immunoglobulin) in the past, failed (poor efficacy, or failure to maintain efficacy, or relapse), or had contraindications, intolerance, or refusal of first-line treatment.
* Treatment for ITP (including but not limited to glucocorticoids, recombinant human thrombopoietin (rTPO)) must be completed before enrollment, or the dose must be stable or in a phase of reduction within 2 weeks before enrollment. Immunosuppressants (including but not limited to azathioprine, danazol, cyclosporine A, mycophenolate mofetil) must be finished before entering the group, or the dose must be stable or in the reduction period within 3 months before entering the group.
* Effective contraceptive measures will be taken during the clinical trial.

Exclusion Criteria:

* Thrombocytopenia secondary to thyroid disease.
* Patients with any prior history of arterial or venous thrombosis, and with any of the following risk factors: cancer, Factor V Leiden, ATIII deficiency, and antiphospholipid syndrome.
* Those who had received anti-CD20 monoclonal antibody within 6 months or who had previously failed to respond to low-dose anti-CD20 monoclonal antibody.
* Patients who had failed to respond to the previous use of eltrombopag 75 mg once a day, hetrombopag 7.5mg once a day or avatrombopag 40mg once a day for more than 4 weeks.
* Patients who have received splenectomy within one year or have splenectomy plan within one year.
* Patients with lupus encephalopathy or lupus nephritis.
* Patients with cataract.
* Patients with infectious fever (including but not limited to pulmonary infection) within 1 month or with active infection during screening.
* Existing hepatitis B virus, hepatitis C virus replication or HIV infection.
* Patients with agranulocytosis (ANC \<1× 10\^9/L), or moderate and severe anemia (HGB \< 90g/L). For patients with Evans syndrome, patients with HGB\< 60g/L will be excluded.
* Severe liver dysfunction (alanine aminotransferase or glutamic oxaloacetic transaminase \> 3×ULN), or bilirubin level \> 2×ULN except patients with Evans syndrome.
* Patients with severe cardiac or pulmonary dysfunction.
* Severe renal damage (creatinine clearance \< 50 ml/min).
* There were surgical planners during the study.
* History of psychiatric disorder.
* Pregnant or lactating women or those planning to be pregnant during the trial.
* Patients with a history of drug/alcohol abuse (within 2 years before the study).
* Patients that have participated in other experimental researches within one month before enrollment.
* Any other circumstances that the investigator considers that the patient is not suitable to participate in the trial.

Primary outcomes:
measure: Platelet response
timeFrame: From the start of study treatment (Day 1) up to the end of week 24
Secondary outcomes:
measure: Platelet response
timeFrame: From the start of study treatment (Day 1) up to the end of week 4, 8 and 12
measure: Platelet response
timeFrame: From the start of study treatment (Day 1) up to the end of week 4, 8 and 12
measure: Time to platelet response
timeFrame: From the start of study treatment (Day 1) up to the end of week 24
measure: Duration of platelet response
timeFrame: From the start of study treatment (Day 1) up to the end of week 24
measure: Bleeding score
timeFrame: From the start of study treatment (Day 1) up to the end of week 24
measure: ITP-Patient Assessment Questionnaire
timeFrame: From the start of study treatment (Day 1) up to the end of week 24
measure: Changes of disease activity index in patients with systemic lupus erythematosus
timeFrame: From the start of study treatment (Day 1) up to the end of week 24
measure: The improvement of symptoms
timeFrame: From the start of study treatment (Day 1) up to the end of week 24
measure: Improvement in immune indexes
timeFrame: From the start of study treatment (Day 1) up to the end of week 24
measure: Discontinuation rate of glucocorticoids
timeFrame: From the start of study treatment (Day 1) up to the end of week 24
measure: Hemoglobin response
timeFrame: From the start of study treatment (Day 1) up to the end of week 24
measure: Hemoglobin response
timeFrame: From the start of study treatment (Day 1) up to the end of week 24
measure: functional assessment of chronic illness therapy-fatigue
timeFrame: From the start of study treatment (Day 1) up to the end of week 24
Other outcomes:
measure: Incidence of Toxicity
timeFrame: From the start of study treatment (Day 1) up to the end of week 24
Locations:
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
state: Tianjin
Study officials:
affiliation: Institute of Hematology & Blood Diseases Hospital, China
name: Lei Zhang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of Hematology & Blood Diseases Hospital, China
name: Rongfeng Fu
role: PRINCIPAL_INVESTIGATOR
References: