A Clinical Trial to Assess Safety and Efficacy of Daratumumab in the Treatment of Primary Immune Thrombocytopenia

Study Overview
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Brief Summary
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A single-center, open-label, off-label use investigator-initiated clinical study with safety run-in to explore the clinical activity and safety of daratumumab in adult ITP patients who have not responded adequately or relapsed after first-line treatment and at least one second-line therapy including rituximab and/or TPO-RA.

Detailed Description
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Primary immune thrombocytopenia is an autoimmune disease associated with a reduced peripheral blood platelet count. The first-line treatment is corticosteroids. Splenectomy, rituximab, and thrombopoietin receptor agonists (TPO RAs, such as Etrapopar and Romistine) are commonly used as second-line therapy. However, many of the treatments used achieve few lasting remissions. About 20% - 30% of patients have inadequate or no response to first-line and second-line treatment, and would develop into recurrent/refractory (r/r) ITP. A branch of pathogenesis for ITP has been revealed that plasma cells secrete pathogenic antibodies directed against platelet and red blood cell antigens. Antiplatelet specific plasma cells have been detected in the spleen of patients with rituximab refractory ITP. In those refractory cases, persistent autoreactive long-lived plasma cells in the bone marrow could explain treatment failure. Daratumumab, an anti-CD38 monoclonal antibody developed to target tumoral plasma cells in multiple myeloma, was recently found to be effective in antibody-mediated diseases, such as autoimmune cytopenia following hematopoietic stem cell transplantation, systemic lupus and also ITP. This study will evaluate the safety and biologic activity of Daratumumab in r/r primary ITP who fail to respond to at least one previous second-line therapy. The study will enroll approximately 20 participants. This trial will be conducted in China. All participants will be followed for at least 16 weeks after the 8 weeks of treatment.

Official Title
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A Investigator-initiated Clinical Trial to Assess Safety and Efficacy of Daratumumab in the Treatment of Relapsed/Refractory Primary Immune Thrombocytopenia

Conditions
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Immune Thrombocytopenia

Intervention / Treatment
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* Drug: Daratumumab Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged ≥18 years. Diagnosed with ITP that has persisted for ≥3 months and with a platelet count of <30 X 109/L measured within 2 days prior to inclusion. Failure to achieve response or relapse after corticosteroid therapy, and at least one second-line therapy including rituximab. If receiving emergency care for ITP, treatment should be stopped >2 weeks before first dose. A positive result to the ELISA test to detect antibody against GPIIb/IIIa or GPIIb/IIIa and GPIb/IX within 1 week prior to inclusion. With normal hepatic and renal functions. ECOG Performance Status ≤ 2. Exclusion Criteria: Received any treatment of anti-CD38 antibody drug. Has been diagnosed with malignancy and/or liver failure, heart failure and renal failure. Known previous infection or seropositivity for HIV, Hepatitis B, Hepatitis C, Cytomegalovirus, EB virus, Syphilis. Any clinically overt hemorrhage. Has been diagnosed with cardiac disease, arrhythmia and/or severe or uncontrollable hypertension Known pulmonary embolism, thrombosis and/or atherosclerosis. Has been received allogeneic stem cell transplantation or organ transplantation. Patients with history of current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent. Pregnancy or lactation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Daratumumab once a week x 8 doses | Drug: Daratumumab Injection<br>* intravenous daratumumab administration<br>* Other names: Darzalex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate of response after daratumumab treatment | Response defined as platelet count ≥50 x109/L .8 weeks after the first dose. | 9-24 weeks | 
| Safety of daratumumab | Incidence of treatment emergent adverse events after daratumumab treatment | 24 weeks |