Efficacy and Safety of PI3K Inhibitors in Relapsed/Refractory Large Granular T Lymphocytic Leukemia

NCT05676710 | Completed Phase 1

• 1 other identifier: IIT2022068
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

Brief 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 patients with relapsed/refractory large granular T lymphocytic leukemia.

Conditions

Relapsed/Refractory Large Granular T Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Overall response rate: HPR + HCR + CMR

  Percentage of patients with hematological response. 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 weeks

Secondary Outcomes (6)

• Incidence of the adverse event

  8 weeks

• Time to achieve partial hematologic response (HPR)

  8 weeks

• Time to achieve complete hematologic response (HCR)

  8 weeks

• Time to achieve complete molecular response (CMR)

  8 weeks

• Change of the health-related quality of life

  Baseline and 2 cycles of therapy

Study Arms (1)

Experimental

EXPERIMENTAL

PI3K inhibitors

Drug: Linperlisib

Interventions

Linperlisib 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.

Experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female age ≥ 18 years
• Diagnosis of T-cell large granular lymphocytic leukemia (T-LGLL)
• Meet any of the following indications for treatment：
• Hemoglobin \< 100g/L or RBC transfusion dependence
• Neutrophil count \<0.5×10\^9/L or neutrophil count decreased with recurrent infection
• Progressive splenomegaly and/or Massive Splenomegaly
• Combined with autoimmune diseases requiring treatment, such as rheumatoid arthritis, autoimmune thyroiditis, etc.
• 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.

You may not qualify if:

• 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 \<60ml/min
• 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.
• Previously treated with other PI3Kδ inhibitor.
• Pregnant or breast-feeding patients

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead
• YL-Pharma: collaborator

Study Sites (2)

Zhoukou Central Hospital

Zhoukou, Henan, China

Location

Regenerative Medicine Center

Tianjin, Tianjin Municipality, China

Location

Related Publications (1)

• Zhang L, Qiu C, Li R, Shen Y, Tian L, Chang H, Liang Q, Pan H, Gao Z, Li W, Zhao J, Fang L, Yu X, Xu J, Kuang Z, Yuan W, Chu Y, Shi J. KLRG1 re-defines a leukemic clone of CD8 effector T cells sensitive to PI3K inhibitor in T cell large granular lymphocytic leukemia. Cell Rep Med. 2025 Apr 15;6(4):102036. doi: 10.1016/j.xcrm.2025.102036. Epub 2025 Mar 26.

  PMID: 40147444 DERIVED

MeSH Terms

Conditions

Recurrence

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2022
• First Posted: January 9, 2023
• Study Start: February 10, 2023
• Primary Completion: January 30, 2024
• Study Completion: February 14, 2024
• Last Updated: May 29, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)