Relapsed/Refractory Large Granular T Lymphocytic LeukemiaPhase 1NCT05676710
Efficacy and Safety of PI3K Inhibitors in Relapsed/Refractory Large Granular T Lymphocytic Leukemia
A Phase 1 study testing Linperlisib in people with Relapsed/Refractory Large Granular T Lymphocytic Leukemia, run by Institute of Hematology & Blood Diseases Hospital, China at 2 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed/Refractory Large Granular T Lymphocytic Leukemia
- What is being tested?
- Linperlisib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 2 sitesChina
- Study dates
- 10 Feb 2023to 14 Feb 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 12Show fewer
- 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.
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
China2 sites
Regenerative Medicine Center
Tianjin, Tianjin Municipality
Zhoukou Central Hospital
Zhoukou, Henan
About this study
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
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.
- Being tested
- Linperlisib
- Medical subject headings
- Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LinperlisibDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | PI3K inhibitors Receives: Drug: Linperlisib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 8 weeks
Secondary outcomes (6)
Incidence of the adverse event
Use Common Terminology Criteria for Adverse Events (CTCAE) Version 5 to assess the adverse event
Measured: 8 weeks
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
Measured: 8 weeks
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.
Measured: 8 weeks
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
Measured: 8 weeks
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
Measured: Baseline and 2 cycles of therapy
Relapse free survival (RFS)
Duration time was calculated from response to relapse.
Measured: A minimum of 2 years of planned follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2023
- Study start10 Feb 2023
- Primary completion30 Jan 2024
- Study completion14 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Relapsed/Refractory Large Granular T Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by Institute of Hematology & Blood Diseases Hospital, ChinaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- YL-Pharma
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05676710
- Sponsor's protocol ID
- IIT2022068
- Status last verified
- Dec 2023
- First submitted
- 8 Dec 2022
- Last updated
- 29 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40147444
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05676710
- Acronym / sponsor ID
- IIT2022068
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Institute of Hematology & Blood Diseases Hospital, ChinaUniversity, hospital or other
- Collaborators
- YL-Pharma
- Study start
- 10 Feb 2023 (actual)
- Primary completion
- 30 Jan 2024 (actual)
- Study completion
- 14 Feb 2024 (actual)
- First posted
- 9 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: LinperlisibPI3K inhibitors |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Male or female age ≥ 18 years
- Diagnosis of T-cell large granular lymphocytic leukemia (T-LGLL)
- Meet any of the following indications for treatment：
- Failure or intolerance to a first-line therapy
- ECOG performance status ≤2
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LinperlisibElevated 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. | Drug | Experimental |
Primary outcome
Overall response rate: HPR + HCR + CMR
Time frame: 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.
6 secondary outcomes
Incidence of the adverse event
Time frame: 8 weeks
Time to achieve partial hematologic response (HPR)
Time frame: 8 weeks
Time to achieve complete hematologic response (HCR)
Time frame: 8 weeks
Time to achieve complete molecular response (CMR)
Time frame: 8 weeks
Change of the health-related quality of life
Time frame: Baseline and 2 cycles of therapy
Relapse free survival (RFS)
Time frame: A minimum of 2 years of planned follow-up
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2024.
- Derived from this study: PubMed 40147444Zhang 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.
- Individual participant dataSharing planned: No
Related trials for Relapsed/Refractory Large Granular T Lymphocytic Leukemia
Active, not recruitingPhase 1
A Study of Ruxolitinib and Duvelisib in People With Lymphoma
T-cell Lymphomas, NK-Cell Lymphomas
RecruitingPhase 1
A Clinical Study on the Efficacy and Safety of Zeprumetostat in Relapsed/Refractory Large Granular Lymphocyte Leukemia
Large Granular Lymphocyte Leukemia, T-LGL Leukemia
RecruitingObservational study
Tissue, Blood, and Body Fluid Sample Collection From Patients With Hematologic Cancer
Chronic Myeloproliferative Disorders, Leukemia
Active, not recruitingObservational study
Infection Prophylaxis and Management in Treating Cytomegalovirus (CMV) Infection in Patients With Hematologic Malignancies Previously Treated With Donor Stem Cell Transplant
Hematopoietic/Lymphoid Cancer, Accelerated Phase Chronic Myelogenous Leukemia
Active, not recruitingPhase 1/2
Oral Azacitidine for the Treatment of Relapsed or Refractory T-cell Large Granular Lymphocytic Leukemia
T-Cell Large Granular Lymphocyte Leukemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Linperlisib in people with Relapsed/Refractory Large Granular T Lymphocytic Leukemia, run by Institute of Hematology & Blood Diseases Hospital, China at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate: HPR + HCR + CMR (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05676710, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2024.