Daratumumab versus rituximab for children with primary immune thrombocytopenia

A Randomized, Open-label Study To Compare The Efficacy And Safety Of Daratumumab Versus Rituximab in ITP Patients Who Failed or Relapsed After Glucocorticoid Therapy

This study will test whether daratumumab works better than rituximab to increase platelet counts in children aged 6–17 with primary ITP who did not respond to or relapsed after steroid treatment.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 122 (estimated)
• Ages: 6 Years to 18 Years
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (other)
• Drugs / interventions: cyclophosphamide, prednisone, Daratumumab, Rituximab
• Locations: 1 site (Tianjin)
• Trial ID: NCT07362238 on ClinicalTrials.gov

What this trial studies

This randomized, open-label phase 2 trial enrolls children aged 6–17 with primary ITP of at least three months' duration who failed glucocorticoid therapy. Participants are randomly assigned to receive daratumumab (an anti-CD38 monoclonal antibody targeting plasma cells) or rituximab (an anti-CD20 B-cell antibody) and are followed for platelet response, durability of response, need for additional ITP treatments, and adverse events. Platelet counts will be monitored over time with predefined response thresholds and safety assessments to compare efficacy and tolerability between arms. The study aims to determine whether targeting plasma cells with daratumumab produces more durable remissions than B-cell depletion with rituximab in relapsed or refractory pediatric ITP.

Who should consider this trial

Good fit: Children aged 6–17 with primary ITP for at least three months who failed or relapsed after glucocorticoid therapy and have platelet counts below 30×10^9/L are the intended participants.

Not a fit: Patients with newly diagnosed ITP, those who maintain a stable response to first-line steroid therapy, or those with non-immune causes of thrombocytopenia are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, the approach could produce more durable platelet responses, reduce bleeding risk, and lessen the need for ongoing ITP therapies in affected children.

How similar studies have performed: Rituximab has shown variable benefit in pediatric ITP while daratumumab is a newer plasma-cell–targeting approach supported mainly by case reports and limited adult data, so controlled pediatric evidence is currently limited.

Eligibility criteria

Inclusion Criteria:

* Age ≥6，\<18 years, male or female.
* Before enrollment, the subjects have been clinically diagnosed with primary immune thrombocytopenia for no less than three months according to the American Society of Hematology guidelines 2011 Evidence-Based Practice Guideline (Neunert et al. 2011) or the International Consensus Report for the Investigation and Management of Primary Immune Thrombocytopenia (Provan et al. 2010), as applicable locally.
* Patients have failed glucocorticoid therapy (either due to inefficacy, efficacy could not be maintained, or relapse). Patients were required to have a response history (PLT≥50×10\^9/L) to standard first-line treatment of ITP (glucocorticoid and/or intravenous immunoglobulin).
* Subjects with a platelet count of \<30×10\^9/L within the 24 hours prior to the first dose of the study drug; The mean platelet count of at least two separate assessments (at least 1 week apart) \<30×10\^9/L during the screening visit, and no platelet count \> 35×10\^9/L.
* ECOG performance status score of ≤2.
* Enrollment of subjects receiving maintenance therapy with a stable dosage is permitted, including glucocorticoids (≤0.5 mg/kg of prednisone or equivalent) or TPO receptor agonists. However, at the time of enrollment, subjects are restricted to using only one concomitant medication with a stable dose, and the concomitant medication must have been stable for a minimum of 4 weeks prior to the initial infusion of the study drug.
* Subjects and the legal guardian comprehensively understand and can adhere to the study protocol requirements and willingly signed the informed consent form.

Exclusion Criteria:

* Subjects with a history of using CD20 monoclonal antibody or CD38 monoclonal antibody.
* Subjects who are diagnosed with autoimmune hemolytic anemia or various secondary thrombocytopenic disorders.
* Subjects with history of any thrombotic or embolic events or extensive and severe bleeding, such as hemoptysis, major upper gastrointestinal bleeding, intracranial hemorrhage, or the presence of sepsis or other irregular bleeding within the 12 months preceding the initiation of the first dose of study drug.
* Subjects who have participated in any other investigational drug studies (including vaccine studies) or been exposed to other investigational drugs within the first 4 weeks or 5 half-lives (whichever was longer) prior to the first dose of study drug.
* Subjects who have used anticoagulants or any agents with antiplatelet effects, such as aspirin, within 3 weeks prior to the first dose of study drug.
* Subjects who have received emergency treatment for ITP (e.g., methylprednisolone, platelet transfusion, intravenous immunoglobulin infusion, or thrombopoietin receptor agonist therapy) within 2 weeks prior to the first dose of study drug.
* Subjects who have been treated with medications including azathioprine, danazol, dapsone, cyclosporine A, tacrolimus, and sirolimus within 4 weeks prior to the first dose of study drug. Subjects who have receive medications including cyclophosphamide and vindesine within 6 months prior to the first dose of study drug.
* Subjects who have undergone splenectomy within 6 months prior to the first dose of study drug.
* Subjects who have received live vaccines within 4 weeks prior to the first dose of study drug, or plan to receive any live vaccines during the course of the study.
* Subjects who are diagnosed with Myelodysplastic syndromes (MDS); Subjects with a with a history of malignancy within the 5 years prior to screening (excluding completely cured in situ cervical cancer and non-metastatic skin squamous cell carcinoma or basal cell carcinoma).
* Subjects who have undergone allogeneic stem cell transplantation or organ transplantation.
* Subjects with a clinically significant medical history, as perceived by investigators, that will pose risks to subjects' safety during the study or potentially affect the safety or efficacy analyses, includes major clinical histories such as circulatory system abnormalities, endocrine system abnormalities, nervous system diseases, blood system diseases, immune system diseases, mental diseases and metabolic abnormalities and so on. e.g., subjects with acute myocardial infarction, unstable angina pectoris, or severe arrhythmias (multifocal ventricular premature contractions, ventricular tachycardia, or ventricular fibrillation) within the 6 months before screening ; New York Heart Association (NYHA) class III-IV heart failure; subjects who were known to have had moderate or severe persistent asthma or chronic obstructive pulmonary disease within the 5 years prior to screening, or whose condition was currently poorly controlled;
* Subjects with a history of severe recurrent or chronic infections, or acute infections requiring systemic treatment with antibiotics, antiviral drugs, antiparasitic drugs, anti-amoebic drugs, or antifungal drugs within 4 weeks prior to the first dose and during the screening period, or superficial skin infections requiring systemic treatment within one week prior to the first dose of study drug. Notably, after the resolution of the infection, the subject may be re-screened.
* Subjects with a history of known or suspected immunosuppression, including invasive opportunistic infections such as histoplasmosis, listeriosis, coccidioidomycosis, pneumocystis pneumonia, and aspergillosis, even if the infection has resolved; or unusually frequent, recurrent, or prolonged infections (as judged by the investigator).
* Significant laboratory abnormalities during screening included:

  1. Alanine aminotransferase or aspartate aminotransferase greater than three times the upper limit of normal (ULN).
  2. Total bilirubin greater than 1.5 times the ULN (note: subjects diagnosed with Gilbert syndrome based on medical records should not be excluded based on this criterion).
  3. absolute neutrophil count \< 1500/mm3.
  4. hemoglobin \< 9g/dL.
  5. IgG \< 500 mg/dL.
  6. lymphocyte count \< 500/mm3.
  7. Creatinine clearance (CrCl) \< 30 mL/min (i.e., CrCl ≥30 mL/min is allowed)
* Positive for HIV antibodies or syphilis antibodies.
* Subjects test positive for Hepatitis B surface antigen (HBsAg) or subjects test positive for hepatitis B core antibody and HBV-DNA (through polymerase chain reaction testing), or subjects test positive for hepatitis C virus antibody and HCV-RNA during the screening period. Subjects with positive hepatitis B core antibody but negative HBV-DNA can be enrolled, with HBV-DNA monitoring every 4 weeks.
* Any other conditions unsuitable for participation in this study, as assessed by the investigator.

Where this trial is running

Tianjin

• Chinese Academy of Medical Science and Blood Disease Hospital — Tianjin, China (RECRUITING)

Study contacts

• Study coordinator: Lei Zhang, MD

Conditions: Immune Thrombocytopenia, Treatment