This randomized, open-label study aim to compare the efficacy and safety of Daratumumab (anti-CD38 monoclonal antibody) with Rituximab in pediatric ITP patients.This study will be conducted in pediatric ITP patients who had not responded to or had relapsed after previous glucocorticoid treatment.
Pediatric Immune thrombocytopenia (ITP) is an organ-specific autoimmune disease, which is characterized by decreased platelet count and skin and mucosal bleeding. Pediatric ITP is a kind of disease with increased platelet destruction and impaired platelet production caused by autoimmunity. Conventional treatment of pediatric 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 pediatric 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. In view of this, anti-CD38 monoclonal antibody can eliminate LLPC, thereby profoundly reducing the production of pathogenic antibodies and achieving good efficacy. Some pediatric patients in our center have been treated with this Daratumumab (anti-CD38 monoclonal antibody) in the past, with good efficacy and safety. Therefore, we planned to conduct a clinical study to evaluate the safety and efficacy of Daratumumab (anti-CD38 monoclonal antibody) versus rituximab in relapsed pediatric patients with primary immune thrombocytopenia, in order to provide more treatment options for pediatric patients with ITP.
Study Type
INTERVENTIONAL
Allocation
All subjects were randomly assigned to group A (active comparator) and group B (experimental). For subjects in group A (active comparator) , rituximab (375mg/m2) was given once.
All subjects were randomly assigned to group A (active comparator) and group B (experimental). For subjects in group B (experimental), Daratumumab (anti-CD38 monoclonal antibody ) (16mg/kg) was given once a week for eight times.
Chinese Academy of Medical Science and Blood Disease Hospital
Tianjin, China
RECRUITINGOverall response rate at week 12
Overall response rate was defined as either partial response or complete response at week 12. Partial response was characterised by at least two consecutive (≥7 days apart) platelet counts of ≥30 to \<100×10\^9/L, with a minimum doubling from baseline and no bleeding. Complete response was characterised by at least two consecutive (≥7 days apart) platelet counts of ≥100×10\^9/L, with no bleeding.
Time frame: 12 weeks
Complete response rate at week 12
Complete response was characterised by at least two consecutive (≥7 days apart) platelet counts of ≥100×10\^9/L, with no bleeding at week 12.
Time frame: 12 weeks
Partial response rate at week 12
Partial response was characterised by at least two consecutive (≥7 days apart) platelet counts of ≥30 to \<100×10\^9/L, with a minimum doubling from baseline and no bleeding at week 12.
Time frame: 12 weeks
Overall response rate at week24
Overall response rate was defined as either partial response or complete response at week 24. Partial response was characterised by at least two consecutive (≥7 days apart) platelet counts of ≥30 to \<100×10\^9/L, with a minimum doubling from baseline and no bleeding. Complete response was characterised by at least two consecutive (≥7 days apart) platelet counts of ≥100×10\^9/L, with no bleeding.
Time frame: 6 months
Overall response rate at week52
Overall response rate was defined as either partial response or complete response at week 52. Partial response was characterised by at least two consecutive (≥7 days apart) platelet counts of ≥30 to \<100×10\^9/L, with a minimum doubling from baseline and no bleeding. Complete response was characterised by at least two consecutive (≥7 days apart) platelet counts of ≥100×10\^9/L, with no bleeding.
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RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
122
Time frame: 1 year
Long term sustained platelet count response rate
Long term sustained platelet count response rate was defined as proportion of patients with a platelet count ≥30×10\^9/L, with at least doubling from baseline and no bleeding, for at least six of the eight visits between weeks 17 and 24.
Time frame: 6 months
Cumulative durations of platelet counts ≥50×10^9/L and ≥30×10^9/L, at least doubling from baseline
Cumulative durations of platelet counts ≥50×10\^9/L and ≥30×10\^9/L, at least doubling from baseline was defined as time from first two consecutive counts meeting criteria, to first two consecutive counts decreasing to below cut-off
Time frame: 1 year
Response at each visit
Response at each visit was defined as either overall response, partial response, or complete response at each visit. Overall response rate was defined as either partial response or complete response. Partial response was characterised by at least two consecutive (≥7 days apart) platelet counts of ≥30 to \<100×10\^9/L, with a minimum doubling from baseline and no bleeding. Complete response was characterised by at least two consecutive (≥7 days apart) platelet counts of ≥100×10\^9/L, with no bleeding.
Time frame: 1 year
Platelet counts at each visit
Platelet counts at each visit was defined as the platelet counts at each visit
Time frame: 1 year
Time to the first two consecutive platelet counts ≥50×10^9/L
Time to the first two consecutive platelet counts ≥50×10\^9/L was defined as time to first two consecutive platelet counts ≥50×10\^9/L with at least doubling from baseline
Time frame: 1 year
Time to response
Time to response was defined as time to first two consecutive platelet counts ≥30×10\^9/L with at least doubling from baseline
Time frame: 1 year
Rescue treatment
Proportion of patients receiving rescue drugs at each visit throughout the trial
Time frame: 1 year
Concomitant treatment
Changes in concomitant treatment at week12 compared with that at baseline
Time frame: 12 weeks
Changes in world health organization (WHO) bleeding scale
Changes in world health organization (WHO) bleeding scale without rescue treatment. Changes of every subject in WHO bleeding score after 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.
Time frame: 1 year
Adverse events
Incidence, severity, and relationship of treatment emergent adverse events after treatment
Time frame: 1 year