PI3K Inhibitors for the Treatment of Relapsed/Refractory Indolent T/NK-cell Lymphomas

Exploratory Clinical Study of PI3K Inhibitors in the Treatment of Relapsed/Refractory Indolent T/NK-Cell Lymphomas：An Open, Prospective, Exploratory Clinical Trial

Indolent T/NK-cell lymphomas are a heterogeneous group of lymphoproliferative diseases originating from T/NK cells, characterized by slow growth and proliferation, but currently remain incurable. For indolent T/NK-cell lymphomas that are unresponsive to first-line treatment, there are few treatment options available and the prognosis is poor. This study is an open-label, prospective clinical trial aimed at evaluating the feasibility, efficacy, and safety of PI3K inhibitors in the treatment of relapsed/refractory indolent T/NK-cell lymphomas. Patients will be treated with Linperlisib or Duvelisib, with an expected overall response rate of 60% for PI3K inhibitor treatment.

Study Overview

• Status: Recruiting
• Conditions: Lymphoma, T-Cell; T-LGL Leukemia; NK-LGL Leukemia
• Intervention / Treatment: Drug: PI3K inhibitor

Detailed Description

Plan to enroll 51 patients with relapsed/refractory indolent T/NK-cell lymphomas; they will receive PI3K inhibitor treatment (including Linperlisib 80mg QD orally, or Duvelisib 25mg BID orally, with a 28-day cycle. Efficacy will be evaluated once per cycle during the first year, and once every two cycles thereafter. Treatment will continue for up to 24 cycles, or until disease progression, lack of response within the first 6 cycles, or the occurrence of intolerable toxicity, whichever occurs first

• Study Type: Interventional
• Enrollment (Estimated): 51
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shuhua Yi, Doctor; Phone Number: 86-22-23909106; Email: yishuhua@ihcams.ac.cn
• Study Contact Backup: Name: Lugui Qiu, Doctor; Phone Number: 86-22-23909172; Email: qiulg@ihcams.ac.cn

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Recruiting
      • Institute of Hematology & Blood Diseases Hospital
      • Contact: Shuhua Yi, Dr.; Phone Number: 86-022-23909106; Email: yishuhua@ihcams.ac.cn
      • Contact: Lugui Qiu, Dr.; Phone Number: 86-022-23909286; Email: qiulg@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

the proportion of patients whose tumors have not progressed after treatment over a specific period of time. Specifically, DCR includes the percentage of patients who achieve complete response (CR), partial response (PR), and stable disease (SD).

Exclusion Criteria:

Here is the translated text:

1. Subjects who have previously used any PI3K inhibitors;
2. Clinical conditions of dysphagia, malabsorption, or other chronic gastrointestinal diseases that may interfere with compliance and/or absorption of the study drug;
3. Unable to discontinue medications that may prolong the QT interval (such as antiarrhythmic drugs) during the study period;
4. Active viral, bacterial, or fungal infections requiring treatment (e.g., pneumonia);
5. HBV or HCV infection (defined as HBsAg and/or HBcAb positive with HBV DNA copy number ≥ upper limit of normal reference value) or acute or chronic active hepatitis C (HCV) antibody positive;
6. History of immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation, or history of allogeneic bone marrow or hematopoietic stem cell transplantation;
7. Received autologous hematopoietic stem cell transplantation within 90 days before the first dose of study treatment;
8. Presence of severe or uncontrolled cardiovascular disease;
9. Presence of severe concomitant diseases that endanger patient safety or are deemed by the investigator to affect the completion of the study (e.g., uncontrolled hypertension, diabetes, thyroid disease);
10. Pregnant or breastfeeding female patients, or baseline pregnancy test positive for women of childbearing potential;
11. Diagnosed or treated for other malignancies within the past 5 years;
12. Any other condition that the investigator deems unsuitable for participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PI3K inhibitor; Linperlisib 80mg QD orally, or Duvelisib 25mg BID orally	Drug: PI3K inhibitor; Linperlisib 80mg QD orally, or Duvelisib 25mg BID orally, with a 28-day cycle. Efficacy will be evaluated once per cycle during the first year, and once every two cycles thereafter. Treatment will continue for up to 24 cycles, or until disease progression, lack of response within the first 6 cycles, or the occurrence of intolerable toxicity, whichever occurs first

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	complete remission rate+ partial remission rate	up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remession rate	Hematological PR was defined as an improvement in blood counts ANC > 0.5 × 109/L; HGB increased by >1 g/dL; PLT > 50 × 109/L	up to 5 years
Overall survival	The time from the start of treatment to the patient's death from any cause	up to 5 years
Duration of remission	the time from response to progression/death (P/D)	up to 5 years
The safety of PI3K inhibitors	Incidence of adverse events, serious adverse events and significant adverse event	up to 5 years
Time to response	from the start of treatment to the first observed partial remission	up to 5 years
Progression-free survival	the time from treatment initiation until disease progression or death	up to 5 years
Disease control rate	the proportion of patients whose tumors have not progressed after treatment over a specific period of time. Specifically, DCR includes the percentage of patients who achieve complete response (CR), partial response (PR), and stable disease (SD).	up to 5 years

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China
• Investigators: Principal Investigator: Shuhua Yi, Doctor, Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2024
• Primary Completion (Estimated): August 10, 2026
• Study Completion (Estimated): July 10, 2028

Study Registration Dates

• First Submitted: July 28, 2024
• First Submitted That Met QC Criteria: July 28, 2024
• First Posted (Actual): July 31, 2024

Study Record Updates

• Last Update Posted (Actual): August 12, 2025
• Last Update Submitted That Met QC Criteria: August 11, 2025
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: PI3K inhibitor; Indolent T/NK-cell lymphomas
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Leukemia, Lymphoid; Leukemia, T-Cell; Leukemia; Lymphoma; Lymphoma, T-Cell; Leukemia, Large Granular Lymphocytic
• Other Study ID Numbers: IIT2024026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No