To evaluate the safety and efficacy of Anti-CD38 Antibody in the treatment of primary immune thrombocytopenia in patients who have failed first-line 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. However, targeting LLPC becomes a new strategy to treat autoimmune diseases. Daratumumab, a kind of 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 daratumumab in the treatment of autoimmune diseases, including membranous nephropathy, systemic lupus erythematosus (SLE) and ITP, are also being carried out simultaneously. The investigators 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 daratumumab in the treatment of immune thrombocytopenia in patients who are steroid-refractory or steroid-dependent.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
intravenous Daratumumab administration This study adopts a prospective, single arm, open design method. Thirty subjects were enrolled in the study and were treated with CD38 monoclonal antibody (Daratumumab 16mg/kg/w) for 4 weeks. The first stage is the main research stage (d1-w4), which is the core treatment period. The subjects will receive intravenous infusion of 16mg/kg Daratumumab once a week for 4 weeks to observe the safety and efficacy during treatment. The second stage (w5-w24) is the stage of withdrawal from the visit, mainly to observe the safety and continuous efficacy of Daratumumab after treatment.
Chinese Academy of Medical Science and Blood Disease Hospital
Tianjin, Tianjin Municipality, China
RECRUITINGEfficacy after Daratumumab treatment within 8 weeks
Evaluation of ORR (overall response rate) within 8 weeks 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: 8 weeks
CR (complete remission) ratios at each visit time point
Evaluation of CR(complete remission) ratios at each visit time point 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: 24 weeks
ORR (overall response rate) at each visit time point
Evaluation of ORR (overall response rate) at each visit time point 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: 24 weeks
Other efficacy evaluation
Proportion of subjects achieving platelet counts ≥ 50×10\^9/L at least once in absence of rescue therapy, and without having had dose increment of TPO-RA or corticosteroids at each visit time point
Time frame: 24 weeks
Time to response (TTR)
Duration from treatment initiation to platelet count ≥30×10\^9/L and at least twice the baseline without having received any platelet elevating therapy or having had dose increment of TPO-RA and/or corticosteroids
Time frame: 24 weeks
Sustained response time-1
The cumulative time of platelet count ≥ 30 × 10\^9/L and at least twice the baseline platelet count during the study period.
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Time frame: 24 weeks
Sustained response time-2
The cumulative time of platelet count ≥ 50 × 10\^9/L during the study period.
Time frame: 24 weeks
Emergency treatment
Percentage of patients who need emergency treatment during the study period.
Time frame: 24 weeks
Reduction of concomitant drug after anti-CD38 antibody treatment within 12 weeks
Percentage of patients with reduced doses of corticosteroids and/or other concomitant immunosuppressive drugs at baseline by 12 weeks of anti-CD38 antibody treatment
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 anti-CD38 monoclonal antibody 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
Number of subjects with clinically significant bleeding as assessed using the bleeding scale for pediatric patients with ITP
Changes of the subjects' numbers in bleeding score after Anti-CD38 antibody treatment according to the reported bleeding scale for pediatric patients with ITP at week 12. The bleeding scale for pediatric patients with ITP is a measure of bleeding severity with the following grades: Grade 1 (minor) Minor bleeding, few petechiae (≤100 total) and/or ≤5 small bruises (≤3 cm in diameter), no mucosal bleeding;Grade 2 (mild) Mild bleeding, many petechiae (\>100 total) and/or \>5 large bruises (\>3 cm in diameter), no mucosal bleeding;Grade 3 (moderate) Moderate bleeding, overt mucosal bleeding, troublesome lifestyle;Grade 4 (severe) Severe bleeding, mucosal bleeding leading to decrease in Hb\>2 g/dL or suspected internal hemorrhage;
Time frame: 12 weeks
Adverse events of Anti-CD38 antibody treatment
Incidence, severity, and relationship of treatment emergent adverse events after Anti-CD38 antibody treatment
Time frame: 24 weeks