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

NCT ID: NCT06224257

Last Updated: 2025-08-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-03
• Study Completion Date: 2026-01-31

Brief Summary

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.

Conditions

Relapsed/Refractory Large Granular T Lymphocytic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Linperlisib

Linperlisib was administered at 80 mg every day, orally in a 28-day cycle until disease progression or intolerable toxicity occurred.

Group Type: EXPERIMENTAL

Linperlisib

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

PI3K Inhibitor

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

YL-Pharma

UNKNOWN

Sponsor Role: collaborator

Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jun Shi, PhD

Role: PRINCIPAL_INVESTIGATOR

Institute of Hematology & Blood Diseases Hospital, China

Locations

Anhui Provincial Hospital

Hefei, Anhui, China

Site Status: RECRUITING

Zhoukou Central Hospital

Zhoukou, Henan, China

Site Status: RECRUITING

Regenerative Medicine Center

Tianjin, Tianjin Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jun Shi, PhD

Role: CONTACT

shijun@ihcams.ac.cn

13752253515

Lele Zhang, PhD

Role: CONTACT

zhanglele@ihcams.ac.cn

15811139278

Facility Contacts

Xiaoyu Zhu

Role: primary

xiaoyuz@ustc.edu.cn

Qian Liang, PhD

Role: primary

lqw141230@163.com

15703815972

Lele Zhang

Role: primary

zhanglele@ihcams.ac.cn

15811139278

Other Identifiers

IIT2023083

Identifier Type: -

Identifier Source: org_study_id