Anti-CD38 Antibody Treating Pediatric Primary Immune Thrombocytopenia (ITP)

NCT ID: NCT06168851

Last Updated: 2025-11-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-28
• Study Completion Date: 2030-12-31

Brief Summary

To evaluate the safety and efficacy of Anti-CD38 Antibody in the treatment of pediatric primary immune thrombocytopenia in patients who have not responded adequately or relapsed after first-line treatment and at least one second-line therapy including Anti-CD20 Antibody and/or TPO-RA, or those in whom no other second-line treatment options are suitable.

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.

The main pathogenesis of ITP is the loss of platelet autoantigen immune tolerance, which leads to abnormal activation of humoral and cellular immunity. It is characterized by antibody mediated platelet destruction and insufficient platelet production by megakaryocytes. The residual long-term autoreactive plasma cells may be a source of therapeutic resistance to autoimmune cytopenia. Antiplatelet specific plasma cells have been detected in the spleen of patients with rituximab refractory ITP. Therefore, the strategy of simply eliminating B cells may not work, because LLPC will continue to produce pathogenic antibodies. However, targeting LLPC becomes a new strategy to treat autoimmune diseases.

Anti-CD38 antibody is a new type of monoclonal antibody targeting CD38. It targets plasma cells and has carried out some clinical studies in multiple myeloma, with good therapeutic effects. In addition, the clinical trials of similar CD38 monoclonal antibody drugs, such as daratumumab, in the treatment of autoimmune diseases, including membranous nephropathy, systemic lupus erythematosus (SLE) and ITP, are also being carried out simultaneously. We assume that autologous reaction LLPC may be the cause of treatment failure in some ITP patients. Therefore, the use of CD38 monoclonal antibody to clear long-term surviving plasma cells in ITP patients may be a new strategy for treating ITP patients.

Therefore, the investigators designed this clinical trial to evaluate the safety and efficacy of CD38 monoclonal antibody in the treatment of pediatric immune thrombocytopenia in patients who are steroid-refractory or steroid-dependent, and fail to respond to at least one previous second-line therapy, including Anti-CD20 Antibody and/ or TPO agonist.

Conditions

Immune Thrombocytopenia; Treatment

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental: Intervention (Anti-CD38 antibody)

60 enrolled subjects : once a week x 8 doses

Group Type: EXPERIMENTAL

Anti-CD38 antibody Injection

Intervention Type: DRUG

intravenous Anti-CD38 antibody administration

This study adopts a prospective, single arm, open design method. Twenty subjects were enrolled in the study and were treated with Anti-CD38 antibody (16mg/kg/w) for 8 weeks.

The first stage is the main research stage (d1-w8), which is the core treatment period. The subjects will receive intravenous infusion of 16mg/kg Anti-CD38 antibody once a week for 8 weeks to observe the safety and efficacy during treatment.

The second stage (w9-w24) is the stage of withdrawal from the visit, mainly to observe the safety and continuous efficacy of Anti-CD38 antibody after treatment.

The third stage (w 25 to y 5): Extension visit phase, primarily to observe the long-term safety and sustained efficacy following CD38 monoclonal antibody therapy.

Interventions

Anti-CD38 antibody Injection

intravenous Anti-CD38 antibody administration

This study adopts a prospective, single arm, open design method. Twenty subjects were enrolled in the study and were treated with Anti-CD38 antibody (16mg/kg/w) for 8 weeks.

The first stage is the main research stage (d1-w8), which is the core treatment period. The subjects will receive intravenous infusion of 16mg/kg Anti-CD38 antibody once a week for 8 weeks to observe the safety and efficacy during treatment.

The second stage (w9-w24) is the stage of withdrawal from the visit, mainly to observe the safety and continuous efficacy of Anti-CD38 antibody after treatment.

The third stage (w 25 to y 5): Extension visit phase, primarily to observe the long-term safety and sustained efficacy following CD38 monoclonal antibody therapy.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age 6 years and above, male or female
• Conform to the diagnostic criteria of immune Thrombocytopenia (ITP)
• Diagnosis of ITP ≥3 months, and with a platelet count of <30 X 10^9/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 or TPORAs.
• 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 normal hepatic and renal functions
• 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.

March 26,2024 After approval by the Ethics Committee，age of subjects has been modified to 6 years and above upon enrollment. Approval Number: IIT2023072-EC-2.

Exclusion Criteria

• Allergy to daratumumab or its excipients, or prior treatment with daratumumab that was refractory or achieved a response lasting <6 months；
• Uncontrollable primary diseases of important organs, such as malignant tumors, liver failure, heart failure, renal failure and other diseases;
• HIV positive;
• Accompanied by uncontrollable active infection, including hepatitis B, hepatitis C, cytomegalovirus, EB virus and syphilis positive;
• Accompanied by extensive and severe bleeding, such as hemoptysis, upper gastrointestinal hemorrhage, intracranial hemorrhage, etc.;
• At present, there are heart diseases, arrhythmias that need treatment or hypertension that researchers judge is poorly controlled;
• Patients with thrombotic diseases such as pulmonary embolism, thrombosis and atherosclerosis;
• Those who have received allogeneic stem cell transplantation or organ transplantation in the past;
• Patients with mental disorders who cannot normally obtain informed consent and conduct trials and follow-up;
• Patients whose toxic symptoms caused by pre-trial treatment have not disappeared;
• Other serious diseases that may limit the subject's participation in this test (such as diabetes; Severe cardiac insufficiency; Myocardial obstruction or unstable arrhythmia or unstable angina pectoris in recent 6 months; Gastric ulcer, etc.);
• Patients with septicemia or other irregular severe bleeding;
• Patients taking antiplatelet drugs at the same time;
• Pregnant women, suspected pregnancies (positive pregnancy test for human chorionic gonadotropin in urine at screening) and lactating patients.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Children's Hospital

OTHER

Sponsor Role: collaborator

Tianjin Children's Hospital

OTHER

Sponsor Role: collaborator

Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lei Zhang, MD

Role: PRINCIPAL_INVESTIGATOR

Chinese Academy of Medical Science and Blood Disease Hospital

Locations

Chinese Academy of Medical Science and Blood Disease Hospital

Tianjin, Tianjin Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Ting Sun, MD

Role: CONTACT

sunting@ihcams.ac.cn

+8615822339131

Yunfei Chen, MD

Role: CONTACT

chenyunfei@ihcams.ac.cn

+8618502220788

Facility Contacts

Ting Sun, MD

Role: primary

sunting@ihcams.ac.cn

+86-22-23909009

Yunfei Chen, MD

Role: backup

chenyunfei@ihcams.ac.cn

+86-22-23909009

Other Identifiers

IIT2023072

Identifier Type: -

Identifier Source: org_study_id