Combining TPO-RAs with anti-CD 20 monoclonal antibody for treating pediatric ITP

A Multicenter, Randomized, Open-label StudyTo Compare The Efficacy And Safety Of TPO-RAs Combining Anti-CD 20 Monoclonal Antibody Versus TPO-RAs in Persistent or Chronic Pediatric ITP Patients Who Failed or Relapse After Glucocorticoid Therapy

This study is testing if combining two types of treatments can help children with immune thrombocytopenia who haven't improved with steroids feel better and stay safe.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 166 (estimated)
• Ages: 6 Years to 17 Years
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (Academic / other)
• Drugs / interventions: cyclophosphamide, Rituximab, Ortuzumab
• Locations: 1 site (Tianjin)
• Trial ID: NCT05718856 on ClinicalTrials.gov

What this trial studies

This multicenter, randomized, open-label study aims to compare the efficacy and safety of TPO receptor agonists (TPO-RAs) combined with anti-CD 20 monoclonal antibodies against TPO-RAs alone in pediatric patients with primary immune thrombocytopenia (ITP) who have not responded to glucocorticoid treatment. The study will enroll 166 participants aged 6-17 years, who will be randomized in a 1:1 ratio to receive either treatment. The primary objective is to evaluate treatment efficacy and safety, while secondary objectives include assessing the efficacy in patients with positive autoantibodies and measuring health-related quality of life. Various TPO-RAs and anti-CD 20 monoclonal antibodies will be utilized based on patient needs.

Who should consider this trial

Good fit: Ideal candidates are pediatric patients aged 6-17 years with chronic or persistent ITP who have not responded to previous glucocorticoid therapy.

Not a fit: Patients who have not been diagnosed with ITP or those who have not previously received glucocorticoid treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a more effective treatment option for pediatric patients suffering from chronic ITP.

How similar studies have performed: While there have been studies on TPO-RAs and monoclonal antibodies separately, this specific combination approach is novel and has not been extensively tested in pediatric ITP.

Eligibility criteria

Inclusion Criteria:

1. Age 6-17 years old (including both ends), male and female;
2. Patients aged 6-11 years (including values at both ends) were diagnosed with chronic ITP, and patients aged 12-17 years (including values at both ends) were diagnosed with persistent or chronic ITP, with platelet counts less than 20×109/L;
3. Patients did not respond to glucocorticoid therapy or relapsed. Previous ITP treatment may include, but is not limited to, glucocorticoids, immunomodulators (IVIG), azathioprine, danazole, cyclophosphamide and immunomodulators.
4. Treatment for ITP (including but not limited to glucocorticoids, recombinant human thrombopoietin, TPO agonist (TPO-RA), azathioprine, danazole, cyclosporin A, mycophenate) must be completed or dose stabilized before enrollment, and therapeutic dose should not be increased after enrollment (e.g. The glucocorticoid dose should be stable for ≥14 days and the immunosuppressant dose should be stable for \> 3 months before the first administration of the study drug. TPO drugs should be stopped \> 1 month, TPO-RA drugs should be stopped \> 1 month).
5. No infectious fever (including but not limited to lung infection) in the past 1 month.
6. Laboratory examination of coagulation function should show that the prothrombin time (PT) and activated partial thrombin time (aPTT) values did not exceed 20% of the normal laboratory value range; No history of abnormal coagulation except for ITP.
7. WBC count, neutrophil absolute value and hemoglobin should be within the normal range of laboratory values. No other abnormality except for ITP. Other exceptions except the following:

   * If the anemia is clearly caused by excessive blood loss associated with ITP.
   * If the increase in WBC count/neutrophil absolute value was clearly due to steroid therapy.
8. Understand the study procedure and voluntarily sign the informed consent.

   * For subjects aged 6-7 (including both ends), parents/guardians understand the study procedure and voluntarily sign the informed consent in person, and subjects are encouraged to participate in the informed process and voluntarily sign the informed consent in person;
   * For subjects aged 8-16 (including both ends), parents/guardians and subjects themselves should understand the study procedure and voluntarily sign the informed consent in person;
   * For the minor subjects \> 16 years old, if the subjects rely on their own income as the main source of living, they are regarded as persons with full capacity for civil conduct and can independently carry out legal acts. The subjects can sign informed consent on the premise that they understand the research procedures and are willing to do so;
   * For minor subjects \> 16 years old, if the subjects do not rely on their own income as the main source of living, they cannot be regarded as persons with full capacity for civil conduct and cannot independently carry out legal acts. Parents/guardians and subjects should understand the study procedures and voluntarily sign the informed consent in person.

Exclusion Criteria:

1. Subjects who has any history of arterial/venous thrombosis and the following risk factors including clotting factor V Leiden disease, ATIII deficiency, antiphospholipid syndrome, etc..
2. Subjects known to have failed all standard TPO-RAs treatments.
3. Subjects known to have taken anti-CD20 antibodytreatment within 3 months prior to initial use of the study drug.
4. Within 2 weeks prior to the initial use of the study drug, subjects were treated with medications (including but not limited to aspirin, aspirin containing compounds, clopidogrel, salicylate, and/or NSAIDs) or anticoagulants that had an impact on platelet function for \> 3 consecutive days.
5. Subjects known to have participated in other investigational clinical trials within 3 months prior to first use of investigational drug.
6. Suffering from severe, progressive, uncontrolled kidney, liver, gastrointestinal, endocrine, lung, heart, nervous system, brain or psychiatric disorders.
7. HIV infection with laboratory or clinical diagnosis.
8. Previous history of hepatitis C, chronic hepatitis B infection, or evidence of active hepatitis. Laboratory tests at the screening stage indicate seropositivity for hepatitis C or hepatitis B seropositivity (HBsAg positive). In addition, if HBsAg is negative but HBcAb is positive (regardless of HBsAb status), HBV DNA testing is required, and if positive, the subject should be excluded.
9. During the screening period, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase were more than 1.5 times of the upper limit of normal value, serum creatinine and bilirubin were more than 1.2 times of the upper limit of normal value, and serum albumin was less than 10% of the lower limit of normal value.
10. Bone marrow biopsy results within 6 months before enrollment showed that myelofibrosis score MF≥2.
11. There is a history of abnormal platelet aggregation that may affect the reliability of platelet count measurements.
12. Any medical history or condition that the investigator deems unsuitable for participation in the study.

Where this trial is running

Tianjin

• Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College — Tianjin, China (Recruiting)

Study contacts

• Principal investigator: Lei Zhang, M.D.,Ph.D — Institute of Hematology & Blood Diseases Hospital, China
• Study coordinator: Lei Zhang

Conditions Primary Immune Thrombocytopenia; immune thrombocytopenia; autoantibody; eltrombopag; rituximab