Efficacy and Safety of Linperlisib in Relapsed/Refractory Large Granular T Lymphocytic Leukemia

A Phase 2, Multicenter, Single-arm, Open-label Study on the Efficacy and Safety of PI3K Inhibitors in Relapsed/Refractory Large Granular T Lymphocytic Leukemia

This is a prospective, multicenter, single-arm, phase 2 study. This study aims to evaluate the efficacy and safety of Linperlisib, the PI3K delta inhibitor for patients with relapsed/refractory large granular T lymphocytic leukemia.

Study Overview

• Status: Recruiting
• Conditions: Relapsed/Refractory Large Granular T Lymphocytic Leukemia
• Intervention / Treatment: Drug: Linperlisib

• Study Type: Interventional
• Enrollment (Estimated): 41
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lele Zhang, PhD; Phone Number: ‭15811139278‬; Email: zhanglele@ihcams.ac.cn
• Study Contact Backup: Name: Jun Shi, PhD; Phone Number: 13752253515; Email: shijun@ihcams.ac.cn

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • Recruiting
      • Anhui Provincial Hospital
      • Contact: Xiaoyu Zhu; Email: xiaoyuz@ustc.edu.cn
  • Henan
    • Zhoukou, Henan, China
      • Recruiting
      • Zhoukou Central Hospital
      • Contact: Qian Liang, PhD; Phone Number: 15703815972; Email: lqw141230@163.com
  • Tianjin
    • Tianjin, Tianjin, China
      • Recruiting
      • Regenerative Medicine Center
      • Contact: Lele Zhang; Phone Number: 15811139278; Email: zhanglele@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female age ≥ 18 years
• Diagnosis of T-cell large granular lymphocytic leukemia (T-LGLL)
• Meet any of the following indications for treatment： 1. Hemoglobin < 100g/L or RBC transfusion dependence 2. Neutrophil count <0.5×10^9/L or neutrophil count decreased with recurrent infection 3. Progressive splenomegaly and/or Massive Splenomegaly 4. Combined with autoimmune diseases requiring treatment, such as rheumatoid arthritis, autoimmune thyroiditis, etc. 5. Severe B symptoms
• Failure or intolerance to a first-line therapy
• ECOG performance status ≤2
• Expected survival ≥ 6 months
• Willing and able to comply with the requirements for this study and written informed consent

Exclusion Criteria:

• History of other lymphoproliferative neoplasms
• 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
• Previously received organ or stem cell transplantation
• Patients with active infection within 2 weeks before giving the first dose of medication
• Patients with HBV, HCV, HIV or other infections that require treatment
• History of immunodeficiency, or congenital immunodeficiency disorders
• 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.
• 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 <30ml/min
• History of mental illness
• History of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severe impairment of lung function, etc.
• 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.
• 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: Linperlisib; Linperlisib was administered at 80 mg every day, orally in a 28-day cycle until disease progression or intolerable toxicity occurred.

Drug: Linperlisib; Elevated PI3K activity in T-LGL likely plays an important role in the ability of the pathologic cells to avoid homeostatic apoptosis, since inhibition of this pathway leads to apoptosis in the population of cells harboring the pathologic clone. More importantly, the activity of this pathway may represent a kind of "Achilles heel" for T-LGL in that PI3K inhibitors alone are quite effective at inducing spontaneous apoptosis in the clonal CTLs after a short incubation.; Other Names: PI3K Inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with hematologic remission	Hematological response is evaluated by hemoglobin (Hb), absolute neutrophil count (ANC), platelet count (PLT), absolute lymphocyte count (ALC), absolute large granular lymphocyte count, and blood transfusion.	8-12 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 Use Common Terminology Criteria for Adverse Events (CTCAE) Version 5 to assess the adverse event Use Common Terminology Criteria for Adverse Events (CTCAE) Version 5 to assess the adverse event	8-12 weeks

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China
• Collaborators: YL-Pharma
• Investigators: Principal Investigator: Jun Shi, PhD, Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2023
• Primary Completion (Estimated): October 31, 2025
• Study Completion (Estimated): January 31, 2026

Study Registration Dates

• First Submitted: January 8, 2024
• First Submitted That Met QC Criteria: January 16, 2024
• First Posted (Actual): January 25, 2024

Study Record Updates

• Last Update Posted (Actual): August 5, 2025
• Last Update Submitted That Met QC Criteria: July 31, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia; Leukemia, Lymphoid; Leukemia, T-Cell
• Other Study ID Numbers: IIT2023083

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
• product manufactured in and exported from the U.S.: No