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

Phase 1

Completed

• Conditions: Relapsed/Refractory Large Granular T Lymphocytic Leukemia
• Interventions: Drug: Linperlisib

• Registration Number: NCT05676710
• Lead Sponsor: Institute of Hematology & Blood Diseases Hospital, China

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-12-08
• Study First Submitted QC: 2022-12-22
• Study First Posted: 2023-01-09
• Study Start: 2023-02-10
• Status Verified: 2023-12
• Primary Completion: 2024-01-30
• Study Completion: 2024-02-14
• Last Update Submitted: 2024-05-27
• Last Update Posted: 2024-05-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

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 <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
• Patients considered to be ineligible for the study by the investigator for reasons other than the above

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental	Linperlisib	PI3K inhibitors

Primary Outcome Measures

Name	Time	Method
Overall response rate: HPR + HCR + CMR	8 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Time to achieve partial hematologic response (HPR)	8 weeks	Duration time was calculated from enrollment to achieve HPR. HPR is assessed by Hb, ANC, PLT, ALC, absolute large granular lymphocyte count and blood transfusion
Incidence of the adverse event	8 weeks	Use Common Terminology Criteria for Adverse Events (CTCAE) Version 5 to assess the adverse event
Time to achieve complete hematologic response (HCR)	8 weeks	Duration time was calculated from enrollment to achieve HCR. HCR is assessed by Hb, ANC, PLT, ALC, and absolute large granular lymphocyte count.
Change of the health-related quality of life	Baseline and 2 cycles of therapy	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
Relapse free survival (RFS)	A minimum of 2 years of planned follow-up	Duration time was calculated from response to relapse.
Time to achieve complete molecular response (CMR)	8 weeks	Duration time was calculated from enrollment to achieve CMR. CMR is assessed by Hb, ANC, PLT, ALC, and absolute large granular lymphocyte count

Trial Locations

Locations (2)

Zhoukou Central Hospital; 🇨🇳 Zhoukou, Henan, China

Regenerative Medicine Center; 🇨🇳 Tianjin, Tianjin, China