Clinical trial NCT05676710: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Relapsed/Refractory Large Granular T Lymphocytic Leukemia
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
Collaborators: name: YL-Pharma
First posted: 2023-01-09
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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 \<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

Primary outcomes:
measure: Overall response rate: HPR + HCR + CMR
timeFrame: 8 weeks
Secondary outcomes:
measure: Incidence of the adverse event
timeFrame: 8 weeks
measure: Time to achieve partial hematologic response (HPR)
timeFrame: 8 weeks
measure: Time to achieve complete hematologic response (HCR)
timeFrame: 8 weeks
measure: Time to achieve complete molecular response (CMR)
timeFrame: 8 weeks
measure: Change of the health-related quality of life
timeFrame: Baseline and 2 cycles of therapy
measure: Relapse free survival (RFS)
timeFrame: A minimum of 2 years of planned follow-up
Other outcomes:
Locations:
city: Zhoukou
country: China
facility: Zhoukou Central Hospital
state: Henan
city: Tianjin
country: China
facility: Regenerative Medicine Center
state: Tianjin
Study officials:
References: