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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Immune Thrombocytopenia; Treatment
• Intervention / Treatment: Drug: Obinutuzumab Injection [Gazyva]

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ting Sun, MD; Phone Number: +8615822339131; Email: sunting@ihcams.ac.cn

Study Locations

• China
  • Tianjin, China
    • Recruiting
    • Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
    • Principal Investigator: Lei Zhang, MD
    • Contact: Ting Sun, MD; Phone Number: +8615822339131; Email: sunting@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intervention (Obinutuzumab); 60 enrolled subjects: one infusion

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	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	6 months
Evaluation of sustained response rate after Obinutuzumab treatment within 12 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 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	12 months
Time to onset response	Time to onset response defined as the time needed for subjects to have a platelet count ≥ 30 × 10^9/L and at least 2-fold from baseline at the meanwhile after initial administration in absence of rescue therapy, and without having had dose increment of TPO-RA or corticosteroids during the study period	12 months
Duration of response	The longest duration for which the subject sustained a platelet count ≥ 30 × 10^9/L and at least 2-fold from baseline at the meanwhile after initial administration in absence of rescue therapy, and without having had dose increment of TPO-RA or corticosteroids during the study period	12 months
Emergency treatment after Obinutuzumab treatment within 12 weeks	Percentage of subjects who received emergency treatment after Obinutuzumab treatment within 12 weeks	12 weeks
Reduction of concomitant drug after Obinutuzumab treatment within 12 weeks	Percentage of patients with reduced doses of corticosteroids and/or other concomitant immunosuppressive drugs at baseline by 12 weeks of Obinutuzumab treatment	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	Changes of the subjects' numbers in WHO bleeding score after Anti-CD20 antibody treatment according to the reported World Health Organization's Bleeding Scale. The WHO Bleeding Scale is a measure of bleeding severity with the following grades: grade 0 = no bleeding, grade 1= petechiae, grade 2= mild blood loss, grade 3 = gross blood loss, and grade 4 = debilitating blood loss.	12 weeks
One-year recurrence-free survival rate	Time from the start of treatment to the occurrence of a relapse or death event	12 months
Safety of Anti-CD20 antibody treatment	Incidence, severity, and relationship of treatment emergent adverse events after Anti-CD20 antibody treatment	12 months
Number of subjects with clinically significant bleeding as assessed using the bleeding scale for pediatric patients with ITP after Obinutuzumab treatment within 12 weeks	Changes of the subjects' numbers in bleeding score after Anti-CD20 antibody treatment according to the reported bleeding scale for pediatric patients with ITP. The bleeding scale for pediatric patients with ITP is a measure of bleeding severity with the following grades: Grade 1 (minor) Minor bleeding, few petechiae (≤100 total) and/or ≤5 small bruises (≤3 cm in diameter), no mucosal bleeding；Grade 2 (mild) Mild bleeding, many petechiae (>100 total) and/or >5 large bruises (>3 cm in diameter), no mucosal bleeding；Grade 3 (moderate) Moderate bleeding, overt mucosal bleeding, troublesome lifestyle；Grade 4 (severe) Severe bleeding, mucosal bleeding leading to decrease in Hb>2 g/dL or suspected internal hemorrhage；	12 weeks
Health-related quality of life survey of subjects(HRQoL)-1	In all participants ,use ITP-PAQ (ITP Patient Assessment Questionnaire) to assess the HRQoL before and after treatment.	12 months
Health-related quality of life survey of subjects(HRQoL)-2	In all participants ,use FACIT-F（functional assessment of chronic illness therapy- fatigue）to assess the HRQoL before and after treatment.	12 months
Health-related quality of life survey of subjects(HRQoL)-3	In all participants ,use Kids' ITP tool KIT、to assess the HRQoL before and after treatment.	12 months
Health-related quality of life survey of subjects(HRQoL)-4	In all participants ,use Pediatric Quality of Life Inventory PedsQL to assess the HRQoL before and after treatment.	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prognostic model establishment using multi-omics data such as transcriptome, proteome, metabolome, microbiome, et al.	The prognosis related factors will be selected from multi-omics data such as transcriptome, proteome, metabolome, microbiome, et al. And then selected prognosis related factors will be used to establish prognosis prediction model	12 months

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China
• Investigators: Principal Investigator: lei zhang, MD, Chinese Academy of Medical Science and Blood Disease Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2023
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: October 13, 2023
• First Submitted That Met QC Criteria: October 17, 2023
• First Posted (Actual): October 23, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 20, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cytopenia; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Skin Manifestations; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Thrombocytopenia; Purpura, Thrombocytopenic, Idiopathic; Antineoplastic Agents, Immunological; Antineoplastic Agents; Obinutuzumab
• Other Study ID Numbers: IIT2023047

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Researchers qualified can request the dataset, including de-identified individual subject data. Data may be requested from PI from 12 months 36 months after study completion.
• IPD Sharing Time Frame: 12 months to 36 months after study completion
• IPD Sharing Access Criteria: Upon request to PI
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No