This randomized, open-label study aim to compare the efficacy and safety of rituximab combining anti-CD38 monoclonal antibody with rituximab in ITP patients.This study will be conducted in ITP patients who had not responded to or had relapsed after previous glucocorticoid treatment.
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. In view of this, the investigators expected that the combination of rituximab and anti-CD38 monoclonal antibody could simultaneously eliminate CD20 positive B cells and LLPC, thereby profoundly reducing the production of pathogenic antibodies and increasing the efficacy of ITP treatment. Some patients have been treated with this regimen in the past, with good efficacy and safety. Therefore, the investigators planned to conduct a clinical study to evaluate the safety and efficacy of rituximab combined with Daratumumab(anti-CD38 monoclonal antibody)versus rituximab in relapsed adult patients with primary immune thrombocytopenia, in order to provide more treatment options for patients with ITP.
Study Type
INTERVENTIONAL
All subjects were randomly assigned to group A (active comparator) and group B (experimental). For subjects in group B (experimental), rituximab (375mg/m2) was given once (day1) and Daratumumab (16mg/kg) was given four times (day8,15,22,29).
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. For subjects in group B (experimental), rituximab (375mg/m2) was given once (day1) and anti-CD38 monoclonal antibody (16mg/kg) was given four times (day8,15,22,29).
Chinese Academy of Medical Science and Blood Disease Hospital
Tianjin, Tianjin Municipality, China
RECRUITINGOverall response rate at week 12
Overall response rate was defined as proportion of subjects with a platelet count ≥ 30 × 10\^9/L and at least twice the baseline platelet count without bleeding and subjects with a platelet count ≥ 100 × 10\^9/L without bleeding at week 12 after initial administration in absence of rescue therapy, and without having had dose increment of TPO-RA or corticosteroids during the study period.
Time frame: 12 weeks
Complete remission rate at week 12
Complete remission rate was defined as proportion of subjects with a platelet count ≥ 100 × 10\^9/L without bleeding at week 12 after initial administration in absence of rescue therapy, and without having had dose increment of TPO-RA or corticosteroids during the study period.
Time frame: 12 weeks
Partial remission rate at week 12
Partial remission rate was defined as proportion of subjects with a platelet count ≥ 30 × 10\^9/L and at least twice the baseline platelet count without bleeding at week 12 after initial administration in absence of rescue therapy, and without having had dose increment of TPO-RA or corticosteroids during the study period.
Time frame: 12 weeks
Overall response rate at month 6
Overall response rate was defined as proportion of subjects with a platelet count ≥ 30 × 10\^9/L and at least twice the baseline platelet count without bleeding and subjects with a platelet count ≥ 100 × 10\^9/L without bleeding at month 6 after initial administration in absence of rescue therapy, and without having had dose increment of TPO-RA or corticosteroids during the study period.
Time frame: 6 months
Overall response rate at month 12
Overall response rate was defined as proportion of subjects with a platelet count ≥ 30 × 10\^9/L and at least twice the baseline platelet count without bleeding and subjects with a platelet count ≥ 100 × 10\^9/L without bleeding at month 12 after initial administration in absence of rescue therapy, and without having had dose increment of TPO-RA or corticosteroids during the study period.
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Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
160
Time frame: 12 months
Sustained response rate at month 6
Proportion of subjects who keep a platelet count ≥ 30 × 10\^9/L and at least twice the baseline platelet count without bleeding and subjects who keep a platelet count ≥ 100 × 10\^9/L without bleeding at month 6 after initial administration.
Time frame: 6 months
Sustained response rate at month 12
Proportion of subjects who keep a platelet count ≥ 30 × 10\^9/L and at least twice the baseline platelet count without bleeding and subjects who keep a platelet count ≥ 100 × 10\^9/L without bleeding at month 12 after initial administration.
Time frame: 12 months
Time to response (TTR)
Time needed from treatment initiation to platelet count ≥30×10\^9/L and at least twice the baseline platelet count.
Time frame: 12 months
Maintenance time
Time from response to relapse.
Time frame: 12 months
Rescue treatment
Percentage of patients who need rescue treatment within 12 weeks during the study period.
Time frame: 12 weeks
Concomitant maintenance drug
Changes in concomitant maintenance therapy at week12 compared with that before the study.
Time frame: 12 weeks
Number of subjects with clinically significant bleeding as assessed using the world health organization (WHO) bleeding scale
Changes of the subjects' numbers in WHO bleeding score after treatment according to the reported World Health Organization's Bleeding Scale at week 12. 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: 12 weeks
Adverse events assessment
Incidence, severity, and relationship of treatment emergent adverse events during the study period
Time frame: 12 months