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

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

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.

Study Overview

• Status: Terminated
• Conditions: Autoimmune Hemolytic Anemia; Failure of Two Rounds of Treatment
• Intervention / Treatment: Drug: Linperlisib

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Henan
    • Zhoukou, Henan, China
      • Zhoukou Central Hospital
  • Tianjin
    • Tianjin, Tianjin, China
      • Regenerative Medicine Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: PI3K Delta Inhibitor

Drug: Linperlisib; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China
• Collaborators: YL-Pharma

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2023
• Primary Completion (Actual): January 31, 2024
• Study Completion (Actual): February 6, 2024

Study Registration Dates

• First Submitted: December 7, 2022
• First Submitted That Met QC Criteria: December 22, 2022
• First Posted (Actual): January 9, 2023

Study Record Updates

• Last Update Posted (Estimated): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Anemia; Hemolysis; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune
• Other Study ID Numbers: PI3K-AIHA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No