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

Phase 2RecruitingNCT06094881

Institute of Hematology & Blood Diseases Hospital, China60 enrolled

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Immune Thrombocytopenia Treatment

Interventions

Obinutuzumab Injection [Gazyva]DRUG

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 withdrawal from the visit, mainly to observe the safety and continuous efficacy of Obinutuzumab after treatment.

Eligibility

Sex: ALLMin age: 12 YearsMax age: 18 Years

Medical Language ↔ Plain English

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.

Locations (1)

Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Tianjin, China

RECRUITING

Outcomes

Primary Outcomes

Evaluation of overall efficacy response after Obinutuzumab treatment within 12 weeks

Overall response rate defined as proportion of subjects with a platelet count ≥ 30 × 10\^9/L and at least 2-fold from baseline at the meanwhile within 12 weeks after initial administration in absence of rescue therapy, and without having had dose increment of TPO-RA or corticosteroids during the study period

Time frame: 12 weeks

Secondary Outcomes

Evaluation of overall efficacy response after Obinutuzumab treatment within 8 weeks

Overall response rate defined as proportion of subjects with a platelet count ≥ 30 × 10\^9/L and at least 2-fold from baseline at the meanwhile within 8 weeks after initial administration in absence of rescue therapy, and without having had dose increment of TPO-RA or corticosteroids during the study period

Time frame: 8 weeks

Evaluation of overall efficacy response after Obinutuzumab treatment within 6 months

Overall response rate defined as proportion of subjects with a platelet count ≥ 30 × 10\^9/L and at least 2-fold from baseline at the meanwhile within 6 months after initial administration in absence of rescue therapy, and without having had dose increment of TPO-RA or corticosteroids during the study period

Time frame: 6 months

Evaluation of overall efficacy response after Obinutuzumab treatment within 12 months

Overall response rate defined as proportion of subjects with a platelet count ≥ 30 × 10\^9/L and at least 2-fold from baseline at the meanwhile within 12 months after initial administration in absence of rescue therapy, and without having had dose increment of TPO-RA or corticosteroids during the study period

Time frame: 12 months

Evaluation of sustained response rate after Obinutuzumab treatment within 6 months

Sustained response rate defined as proportion of subjects who keep a platelet count ≥ 30 × 10\^9/L and at least 2-fold from baseline at the meanwhile at 6 months after initial administration in absence of rescue therapy, and without having had dose increment of TPO-RA or corticosteroids during the study period

Central Contacts

Ting Sun, MD

CONTACT

+8615822339131 sunting@ihcams.ac.cn

Data from ClinicalTrials.gov

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