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

Autoimmune Hemolytic Anemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05676697
• Other study ID #: PI3K-AIHA
• Status: Terminated
• Phase: Phase 1
• Start date: January 13, 2023
• Est. completion date: February 6, 2024

Study information

• Verified date: February 2024
• Source: Institute of Hematology & Blood Diseases Hospital, China
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: February 6, 2024
• Est. primary completion date: January 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 PI3Kd inhibitor.
• Pregnant or breast-feeding patients
• Patients considered to be ineligible for the study by the investigator for reasons other than the above

Related Conditions & MeSH terms

• Anemia
• Anemia, Hemolytic
• Anemia, Hemolytic, Autoimmune
• Autoimmune Hemolytic Anemia
• Hemolysis

Intervention

Drug:
• Linperlisib
The phosphatidylinositol 3-kinase delta (PI3Kd) 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.

Locations

Country	Name	City	State
China	Regenerative Medicine Center	Tianjin	Tianjin
China	Zhoukou Central Hospital	Zhoukou	Henan

Sponsors (2)

Lead Sponsor	Collaborator
Institute of Hematology & Blood Diseases Hospital, China	YL-Pharma

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Incidence of the adverse event	Use Common Terminology Criteria for Adverse Events (CTCAE) Version 5 to assess the adverse event.	12 weeks
Secondary	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
Secondary	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
Secondary	Mean change from baseline in hemoglobin (Hgb) levels		6-12 weeks
Secondary	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
Secondary	Time to achieve complete response (CR)	Duration time was calculated from enrollment to CR.	6-12 weeks
Secondary	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