PI3K Delta Inhibitor in Relapsed / Refractory Autoimmune Hemolytic Anemia Patients After Receiving Two or More Lines of Therapy

Study Overview
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Brief Summary
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This is a prospective, multicenter, single-arm, pilot study. The aim of this study is to evaluate the efficacy and safety of Linperlisib, the PI3K delta inhibitor for autoimmune hemolytic anemia patients who failed the second line therapy.

Official Title
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Safety and Efficacy Study of PI3K Delta Inhibitor in Relapsed / Refractory Autoimmune Hemolytic Anemia Patients After Receiving Two or More Lines of Therapy

Conditions
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Autoimmune Hemolytic Anemia, Failure of Two Rounds of Treatment

Intervention / Treatment
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* Drug: Linperlisib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female age ≥ 18 years Diagnosis of primary warm antibody hemolytic anemia (AIHA). Hemoglobin < 100g/L Refractory to or relapsed after at least 2 prior treatment line. ECOG performance status ≤ 2 Willing and able to comply with the requirements for this study and written informed consent. Exclusion Criteria: Neutrophils counts < 0.5×10^9/L or platelet counts < 50 x 10^9/L Diagnosis of any of the following diseases: Cold agglutinin disease, cold agglutinin syndrome, mixed AIHA, paroxysmal cold hemoglobinuria (PCH). Diagnosis of the active stage of the connective tissue or systemic autoimmune rheumatic diseases (SARDs) History of lymphoproliferative neoplasms Had other inherited or acquired hemolytic diseases. Secondary AIHA caused by drugs or infection Previously received organ or stem cell transplantation. Had malignant tumor within 5 years before enrollment, exclusive of cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial tumor, cervical carcinoma in situ or other indolent tumors Patients with HBV, HCV, HIV or other infections that require treatment. Abnormal liver function: two consecutive examinations with an interval of ≥1 week suggest that ALT and AST are 2.5 times higher than the upper limit of normal values Renal impairment: creatinine clearance <60ml/min Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study, including clinically significant cardiac diseases, refractory hypertension, metabolic disorders and other diseases that seriously affect the function of the gastrointestinal tract. Had a history of any psychiatric diseases, cerebrovascular disease or cognitive sequelae of head injury. Received rituximab in 6 weeks before enrollment. Received attenuated vaccine 4 in weeks before enrollment Participation in another clinical trial within 4 weeks before the start of this trial Have an allergy to Linperlisib or any other part of this medicine. Previously treated with other PI3Kδ inhibitor. Pregnant or breast-feeding patients Patients considered to be ineligible for the study by the investigator for reasons other than the above

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PI3K Delta Inhibitor<br> | Drug: Linperlisib<br>* The phosphatidylinositol 3-kinase delta (PI3Kδ) signaling pathway plays a critical role in the activation, proliferation, and tissue homing of self-reactive B cells that contribute to autoimmune diseases. B cells play an essential role in immune system function and dysfunction (e.g., autoimmunity) by producing antibodies and by acting as antigen-presenting cells (APCs) for T cells. Signaling via PI3K controls many essential B cell functions and is therefore a promising target for preventing aberrant B cell activation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | Percentage of patients with hematological response. Hematological response is evaluated by hemoglobin and other hemolysis-related laboratory indicators. | 6-12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of the adverse event | Use Common Terminology Criteria for Adverse Events (CTCAE) Version 5 to assess the adverse event. | 12 weeks | 
| Complete response rate | Percentage of patients with hematological complete response. Hematological response is evaluated by hemoglobin and other hemolysis-related laboratory indicators. | 6-12 weeks | 
| Complete response with incomplete hemolysis recovery, CRi | Percentage of patients with CRi which is evaluated by hemoglobin and other hemolysis-related laboratory indicators. | 6-12 weeks | 
| Mean change from baseline in hemoglobin (Hgb) levels |  | 6-12 weeks | 
| Time to achieve partial response (PR) | Duration time was calculated from enrollment to PR. PR is assessed by hemoglobin and blood transfusion. | 6-12 weeks | 
| Time to achieve complete response (CR) | Duration time was calculated from enrollment to CR. | 6-12 weeks | 
| Change of the health-related quality of life | Medical Outcomes Study Questionnaire Short Form 36 Health Survey (SF-36) is used to assess the health-related quality of life of patients. The SF-36 has eight scaled scores; the scores are weighted sums of the questions in each section. Scores range from 0 - 100. Lower scores = more disability, higher scores = less disability | Baseline and 12 weeks |