A Prospective, One-arm and Open Clinical Study of Obinutuzumab in the Treatment of Pediatric Primary Immune Thrombocytopenia (ITP)

Official title

A Prospective, One-arm and Open Clinical Study to Assess Safety and Efficacy of Anti-Human CD20 Monoclonal Antibody Obinutuzumab in the Treatment of Pediatric Primary Immune Thrombocytopenia

Overview

To evaluate the safety and efficacy of Obinutuzumab in the treatment of pediatric primary immune thrombocytopenia in patients who have not responded adequately or relapsed after first-line glucocorticoid treatment.

Detailed description

Immune thrombocytopenia (ITP) is an organ-specific autoimmune disease, which is characterized by decreased platelet count and skin and mucosal bleeding. ITP is a kind of disease with increased platelet destruction and impaired platelet production caused by autoimmunity. Conventional treatment of adult ITP includes first-line glucocorticoid and immunoglobulin therapy, second line TPO and TPO receptor agonist, splenectomy and other immunosuppressive treatments (such as rituximab, vincristine, azathioprine, etc.). ITP is one of the most common hemorrhagic diseases. At present, the treatment response of ITP is not good, and a considerable number of patients need drug maintenance treatment, which seriously affects the quality of life of patients and increases the economic burden of patients. Therefore, there is still a lack of effective treatment for adult ITP, especially for recurrent and refractory ITP patients, which is one of the problems that have attracted more attention and need to be solved urgently.

Obinutuzumab is the first personalized type Ⅱ glycosylation engineered CD20 monoclonal antibody. Studies have shown that compared with rituximab, obinutuzumab may improve its efficacy in lymphoma by increasing DCD and ADCC effects and reducing drug resistance by reducing CDC effects. In view of this, Obinutuzumab may have the same effect in the treatment of ITP, and may be more effective in the treatment of ITP, but there is also a risk of poor efficacy. At present, there is a lack of data on the efficacy and safety of Obinutuzumab in the treatment of ITP in China, especiallly pediatric ITP.

Therefore, the investigators designed this clinical trial to evaluate the safety and efficacy of Obinutuzumab in the treatment of pediatric immune thrombocytopenia in patients who have not responded adequately or relapsed after first-line glucocorticoid treatment.

Interventions

• Drug Obinutuzumab Injection [Gazyva]
  intravenous Obinutuzumab administration This study adopts a prospective, single arm, open design method. 60 subjects were enrolled in the study and were treated with CD20 monoclonal antibody (Obinutuzumab: 1000mg) for once. The first stage is the main research stage (d1-w12), which is the core treatment period. The subjects will receive intravenous infusion of 1000mg Obinutuzumab for once to observe the safety and efficacy during treatment. The second stage (w12-w48) is the stage of withdrawa

Primary outcome measures

• Evaluation of overall efficacy response after Obinutuzumab treatment within 12 weeks [Time frame: 12 weeks]

Secondary outcome measures (12)

• Evaluation of overall efficacy response after Obinutuzumab treatment within 8 weeks [Time frame: 8 weeks]
• Evaluation of overall efficacy response after Obinutuzumab treatment within 6 months [Time frame: 6 months]
• Evaluation of overall efficacy response after Obinutuzumab treatment within 12 months [Time frame: 12 months]
• Evaluation of sustained response rate after Obinutuzumab treatment within 6 months [Time frame: 6 months]
• Evaluation of sustained response rate after Obinutuzumab treatment within 12 months [Time frame: 12 months]
• Time to onset response [Time frame: 12 months]
• Duration of response [Time frame: 12 months]
• Emergency treatment after Obinutuzumab treatment within 12 weeks [Time frame: 12 weeks]
• Reduction of concomitant drug after Obinutuzumab treatment within 12 weeks [Time frame: 12 weeks]
• Number of subjects with clinically significant bleeding as assessed using the world health organization (WHO) bleeding scale after Obinutuzumab treatment within 12 weeks [Time frame: 12 weeks]
• Number of subjects with clinically significant bleeding as assessed using the bleeding scale for pediatric patients with ITP after Obinutuzumab treatment within 12 weeks [Time frame: 12 weeks]
• One-year recurrence-free survival rate [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

• Age 12-18 years old, male or female
• Conform to the diagnostic criteria of persistent or chronic immune Thrombocytopenia (ITP)
• With a platelet count of <30 X 10\^9/L measured within 2 days prior to administration（Platelet counts were measured at least 2 times during screening (at least 1 week apart) with platelets<30 X 10\^9/L）
• Failure or recurrence of previous hormonal therapy or hormone dependence
• The previous emergency treatment of ITP (e.g. methylprednisolone, platelet transfusion, IVIG transfusion) must be completed at least 2 weeks before the first administration
• Signed and dated written informed consent
• With Liver and kidney function<1.5×upper limit of normal， such as ALT、AST，BUN，Cre，etc.
• ECOG physical state score ≤ 2 points
• Cardiac function of the New York Society of Cardiac Function ≤ 2
• Patients receiving maintenance treatment (including corticosteroids (less than or equal to 0.5mg/kg prednisone), TPO receptor agonists, etc.) must have a stable dose at least 4 weeks before the first administration, and azathioprine, danazol, cyclosporin A, tacrolimus, sirolimus, etc. must be stopped at least 4 weeks before the first administration; The end of rituximab treatment was>3 months；More than 6 months after splenectomy.

Exclusion criteria

• Subjects with primary disease of important organs (liver, kidney, heart, etc.), or with immune system diseases;
• Secondary thrombocytopenia caused by various reasons, such as connective tissue disorders, bone marrow hematopoietic failure disease, myelodysplastic syndrome, malignancy, drugs, inherited thrombocytopenia, common variable immune deficiency, lymphoma, etc.;
• Subjects infected with human immunodeficiency virus (HIV);
• Uncontrollable or active infections during the screening period, including hepatitis B, hepatitis C, cytomegalovirus, EB virus, or positive syphilis antigen;
• Subjects with extensive and severe bleeding, such as hemoptysis, upper gastrointestinal hemorrhage, intracranial hemorrhage;
• Subjects with heart disease that requires treatment or hypertension that has been judged by researchers to be poorly controlled currently;
• Subjects with any venous or arterial thrombosis, atherosclerosis, and other diseases;
• Subjects with a history of malignant solid tumor or have received allogeneic stem cell transplantation or organ transplantation;
• Subjects with mental disorders who are unable to sign normal informed consent and conduct trials and follow-up;
• Subjects whose toxic symptoms caused by pre-trial treatment have not disappeared;
• Subjects with other serious diseases that may limit their participation in this trial (diabetes; severe cardiac insufficiency; myocardial obstruction or unstable arrhythmia or unstable angina pectoris in the last 6 months; gastric ulcer; active autoimmune disease, etc.);
• Subjects with septicemia or other irregular bleeding;
• Patients taking antiplatelet drugs at the same time;
• Any medical history or condition that the investigator deems unsuitable for participation in the study.

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences a — Tianjin

Identifiers

NCT: NCT06094881 · IIT2023047

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗