Anti-CD20 Monoclonal Antibody, Autoimmune Hemolytic Anemia (AIHA), BTK Inhibitors, Immune Thrombocytopenia (ITP)
Conditions
Brief summary
This study aims to utilize anti-CD20 monoclonal antibodies to eliminate peripheral B cells and reduce the mechanism of autoantibody production, as well as combine the mechanism of BTK inhibitors (BTKi) blocking the B cell receptor signaling pathway and inhibiting B cell activation and proliferation, for the treatment of refractory immune-related cytopenia. In this study, it includes the salvage treatment of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA), expecting to achieve a synergistic and enhancing effect. This study aims to select Zuberitamab, a human-mouse chimeric anti-CD20 monoclonal antibody, and the BTKi Orelabrutinib as combination therapy options. The clinical efficacy of the Zuberitamab-Orelabrutinib combination therapy (overall response rate, duration of sustained remission) will be evaluated, along with its safety profile (including infections, bleeding, cardiac toxicity), to provide a theoretical basis for their combined use in treating refractory immune-related thrombocytopenia (ITP and AIHA).
Interventions
DRUGAnti-CD20 monoclonal antibody and the BTK inhibitor
This is a novel combination regimen of anti-CD20 monoclonal antibody plus BTKi, specifically designed for patients with refractory immune-related cytopenia.
Sponsors
Qi deng
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with refractory immune-related cytopenia, including immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA); * Age ranging from 18 to 80 years old (inclusive of 18 and 80); * Expected survival time \> 12 months; * Good function of major organs: 1. liver function: ALT/AST \< 3 times the upper limit of normal; 2. kidney function: creatinine \< 100 μmol/L; 3. lung function: indoor oxygen saturation ≥ 95%; 4. heart function: left ventricular ejection fraction (LVEF) ≥ 50%; * Peripheral superficial venous blood flow is unobstructed, capable of meeting the requirements for intravenous infusion; * Karnofsky score ≥ 60, ECOG ≤ 2 points.
Exclusion criteria
* Women who are pregnant (with positive urine/blood pregnancy test results) or breastfeeding; * Those who have severe underlying heart diseases when participating in this study, including: 1. clinically significant atrial fibrillation (AF), 2. cardiac conduction block, 3. myocardial infarction (within 1 year), 4. congestive heart failure (CHF); 5. cardiac echocardiography LVEF \< 50%; 6. New York Heart Association (NYHA) cardiac function classification of III-IV grade; * Those with active bleeding or bleeding tendencies, and those who need to take anticoagulant drugs; * Those with organ dysfunction or uncontrollable coexisting diseases; * History of malignant tumors; * Those with active chronic hepatitis B or active hepatitis C; * Known history of human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome; * Those with uncontrollable infectious diseases; * As determined by the investigator, other unsuitable conditions exist.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the Median overall response rate at 6 months of anti-CD20 monoclonal antibody and BTKi combination therapy in refractory immune-related cytopenia | Six month after treatment initiation | Median overall response rate at 6 months after treatment initiation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the early overall response rate 3 months after the start of anti-CD20 monoclonal antibody and BTKi combination therapy in refractory immune-related cytopenia | Three month after therapy | The early overall response rate 3 months after the start of treatment |
| Evaluate the sustained remission rate that lasts for 6 months after achieving remission following anti-CD20 monoclonal antibody and BTKi combination therapy in refractory immune-related cytopenia | Six month after achieving remission | The sustained remission rate that lasts for 6 months after achieving remission |
| Evaluate the Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of anti-CD20 monoclonal antibody and BTKi combination therapy in refractory immune-related cytopenia | Up to three month after therapy | The incidence and severity of therapy related toxic reactions (including infections, bleeding, cardiac toxicity) |
Outcome results
None listed