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

Primary Purpose

Relapsed/Refractory Large Granular T Lymphocytic Leukemia

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Linperlisib
Sponsored by
Institute of Hematology & Blood Diseases Hospital, China
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed/Refractory Large Granular T Lymphocytic Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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: 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. 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

Sites / Locations

  • Zhoukou Central HospitalRecruiting
  • Regenerative Medicine CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental

Arm Description

PI3K inhibitors

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Incidence of the adverse event
Use Common Terminology Criteria for Adverse Events (CTCAE) Version 5 to assess the adverse event
Time to achieve partial hematologic response (HPR)
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
Time to achieve complete hematologic response (HCR)
Duration time was calculated from enrollment to achieve HCR. HCR is assessed by Hb, ANC, PLT, ALC, and absolute large granular lymphocyte count.
Time to achieve complete molecular response (CMR)
Duration time was calculated from enrollment to achieve CMR. CMR is assessed by Hb, ANC, PLT, ALC, and absolute large granular lymphocyte count
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
Relapse free survival (RFS)
Duration time was calculated from response to relapse.

Full Information

First Posted
December 8, 2022
Last Updated
March 14, 2023
Sponsor
Institute of Hematology & Blood Diseases Hospital, China
Collaborators
YL-Pharma
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1. Study Identification

Unique Protocol Identification Number
NCT05676710
Brief Title
Efficacy and Safety of PI3K Inhibitors in Relapsed/Refractory Large Granular T Lymphocytic Leukemia
Official Title
A Single-arm, Open-label, Pilot Study on the Efficacy and Safety of PI3K Inhibitors in Relapsed/Refractory Large Granular T Lymphocytic Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 10, 2023 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
May 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Institute of Hematology & Blood Diseases Hospital, China
Collaborators
YL-Pharma

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed/Refractory Large Granular T Lymphocytic Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental
Arm Type
Experimental
Arm Description
PI3K inhibitors
Intervention Type
Drug
Intervention Name(s)
Linperlisib
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall response rate: HPR + HCR + CMR
Description
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.
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Incidence of the adverse event
Description
Use Common Terminology Criteria for Adverse Events (CTCAE) Version 5 to assess the adverse event
Time Frame
8 weeks
Title
Time to achieve partial hematologic response (HPR)
Description
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
Time Frame
8 weeks
Title
Time to achieve complete hematologic response (HCR)
Description
Duration time was calculated from enrollment to achieve HCR. HCR is assessed by Hb, ANC, PLT, ALC, and absolute large granular lymphocyte count.
Time Frame
8 weeks
Title
Time to achieve complete molecular response (CMR)
Description
Duration time was calculated from enrollment to achieve CMR. CMR is assessed by Hb, ANC, PLT, ALC, and absolute large granular lymphocyte count
Time Frame
8 weeks
Title
Change of the health-related quality of life
Description
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
Time Frame
Baseline and 2 cycles of therapy
Title
Relapse free survival (RFS)
Description
Duration time was calculated from response to relapse.
Time Frame
A minimum of 2 years of planned follow-up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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: 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. 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jun Shi, PhD
Phone
13752253515
Email
shijun@ihcams.ac.cn
Facility Information:
Facility Name
Zhoukou Central Hospital
City
Zhoukou
State/Province
Henan
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qian Liang, PhD
Phone
15703815972
Email
lqw141230@163.com
Facility Name
Regenerative Medicine Center
City
Tianjin
State/Province
Tianjin
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lele Zhang, PhD
Phone
15811139278‬
Email
zhanglele@ihcams.ac.cn

12. IPD Sharing Statement

Plan to Share IPD
No

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

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