Combining TPO-RAs with anti-CD20 antibody for treating immune thrombocytopenia

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

This study is testing if a new combination of medications can help adults with immune thrombocytopenia who haven't responded to other treatments.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 94 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (Academic / other)
• Locations: 1 site (Tianjin, Tianjin)
• Trial ID: NCT04915482 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness and safety of combining thrombopoietin receptor agonists (TPO-RAs) with low-dose anti-CD20 monoclonal antibodies in adults suffering from immune thrombocytopenia (ITP) with autoantibodies who have not responded to first-line treatments. Participants aged 18-65 will be nonrandomly assigned to either the combination therapy or the best available therapy (BAT). The study aims to provide insights into a new treatment approach for patients with ITP secondary to connective tissue diseases and other related conditions.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-65 with immune thrombocytopenia and autoantibodies who have failed first-line treatments.

Not a fit: Patients who are under 18 or over 65 years old, or those who have not previously received first-line treatment for ITP may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new effective option for patients with difficult-to-treat immune thrombocytopenia.

How similar studies have performed: While the combination of TPO-RAs and anti-CD20 antibodies is a novel approach, similar studies have shown promise in treating autoimmune conditions.

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.

Where this trial is running

Tianjin, Tianjin

• Institute of Hematology & Blood Diseases Hospital — Tianjin, Tianjin, China (Recruiting)

Study contacts

• Principal investigator: Lei Zhang, MD — Institute of Hematology & Blood Diseases Hospital, China
• Study coordinator: Rongfeng Fu, MD

Conditions Immune Thrombocytopenia; Autoantibodies; Evan Syndrome; Connective Tissue Diseases