Linperlisib Combination With Cyclophosphamide, Prednisone, and Thalidomide (CPT) in R/R NHL

NCT ID: NCT07195799

Last Updated: 2025-09-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-31
• Study Completion Date: 2027-12-31

Brief Summary

This is a multicenter, open-label, non-randomized, multi-cohort study to evaluate the efficacy and safety of linperlisib combined with cyclophosphamide, prednisone, and thalidomide (CPT) regimen in the treatment of relapsed and/or refractory non-Hodgkin lymphoma.

Conditions

Non-Hodgkin Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PTCL

Group Type: EXPERIMENTAL

Linperlisib combined with CPT regimen

Intervention Type: DRUG

Linperlisib: 80mg QD during the cycle 1-2，80mg QD for the first 7 days of cycle 3-6 (each cycle is 28 days) Cyclophosphamide: 50mg QD during the cycle 1-6 (each cycle is 28 days) Prednisone: 20mg QD during the cycle 1-6 (each cycle is 28 days) Thalidomide: 50mg QD during the cycle 1-6 (each cycle is 28 days) After six cycles, patients with CR or PR continue to receive linperlisib at a dose of 80mg for the first 7 days every cycle (each cycle is 28 days) until disease progression, intolerable toxicity, investigator judgment that treatment should be discontinued, or subject withdrawal of consent, whichever occurred first.

NK/TCL

Group Type: EXPERIMENTAL

Linperlisib combined with CPT regimen

Intervention Type: DRUG

Linperlisib: 80mg QD during the cycle 1-2，80mg QD for the first 7 days of cycle 3-6 (each cycle is 28 days) Cyclophosphamide: 50mg QD during the cycle 1-6 (each cycle is 28 days) Prednisone: 20mg QD during the cycle 1-6 (each cycle is 28 days) Thalidomide: 50mg QD during the cycle 1-6 (each cycle is 28 days) After six cycles, patients with CR or PR continue to receive linperlisib at a dose of 80mg for the first 7 days every cycle (each cycle is 28 days) until disease progression, intolerable toxicity, investigator judgment that treatment should be discontinued, or subject withdrawal of consent, whichever occurred first.

CLL

Group Type: EXPERIMENTAL

Linperlisib combined with CPT regimen

Intervention Type: DRUG

Linperlisib: 80mg QD during the cycle 1-2，80mg QD for the first 7 days of cycle 3-6 (each cycle is 28 days) Cyclophosphamide: 50mg QD during the cycle 1-6 (each cycle is 28 days) Prednisone: 20mg QD during the cycle 1-6 (each cycle is 28 days) Thalidomide: 50mg QD during the cycle 1-6 (each cycle is 28 days) After six cycles, patients with CR or PR continue to receive linperlisib at a dose of 80mg for the first 7 days every cycle (each cycle is 28 days) until disease progression, intolerable toxicity, investigator judgment that treatment should be discontinued, or subject withdrawal of consent, whichever occurred first.

MZL

Group Type: EXPERIMENTAL

Linperlisib combined with CPT regimen

Intervention Type: DRUG

Linperlisib: 80mg QD during the cycle 1-2，80mg QD for the first 7 days of cycle 3-6 (each cycle is 28 days) Cyclophosphamide: 50mg QD during the cycle 1-6 (each cycle is 28 days) Prednisone: 20mg QD during the cycle 1-6 (each cycle is 28 days) Thalidomide: 50mg QD during the cycle 1-6 (each cycle is 28 days) After six cycles, patients with CR or PR continue to receive linperlisib at a dose of 80mg for the first 7 days every cycle (each cycle is 28 days) until disease progression, intolerable toxicity, investigator judgment that treatment should be discontinued, or subject withdrawal of consent, whichever occurred first.

MCL

Group Type: EXPERIMENTAL

Linperlisib combined with CPT regimen

Intervention Type: DRUG

Linperlisib: 80mg QD during the cycle 1-2，80mg QD for the first 7 days of cycle 3-6 (each cycle is 28 days) Cyclophosphamide: 50mg QD during the cycle 1-6 (each cycle is 28 days) Prednisone: 20mg QD during the cycle 1-6 (each cycle is 28 days) Thalidomide: 50mg QD during the cycle 1-6 (each cycle is 28 days) After six cycles, patients with CR or PR continue to receive linperlisib at a dose of 80mg for the first 7 days every cycle (each cycle is 28 days) until disease progression, intolerable toxicity, investigator judgment that treatment should be discontinued, or subject withdrawal of consent, whichever occurred first.

FL

Group Type: EXPERIMENTAL

Linperlisib combined with CPT regimen

Intervention Type: DRUG

Linperlisib: 80mg QD during the cycle 1-2，80mg QD for the first 7 days of cycle 3-6 (each cycle is 28 days) Cyclophosphamide: 50mg QD during the cycle 1-6 (each cycle is 28 days) Prednisone: 20mg QD during the cycle 1-6 (each cycle is 28 days) Thalidomide: 50mg QD during the cycle 1-6 (each cycle is 28 days) After six cycles, patients with CR or PR continue to receive linperlisib at a dose of 80mg for the first 7 days every cycle (each cycle is 28 days) until disease progression, intolerable toxicity, investigator judgment that treatment should be discontinued, or subject withdrawal of consent, whichever occurred first.

Interventions

Linperlisib combined with CPT regimen

Linperlisib: 80mg QD during the cycle 1-2，80mg QD for the first 7 days of cycle 3-6 (each cycle is 28 days) Cyclophosphamide: 50mg QD during the cycle 1-6 (each cycle is 28 days) Prednisone: 20mg QD during the cycle 1-6 (each cycle is 28 days) Thalidomide: 50mg QD during the cycle 1-6 (each cycle is 28 days) After six cycles, patients with CR or PR continue to receive linperlisib at a dose of 80mg for the first 7 days every cycle (each cycle is 28 days) until disease progression, intolerable toxicity, investigator judgment that treatment should be discontinued, or subject withdrawal of consent, whichever occurred first.

Intervention Type: DRUG

Linperlisib combined with CPT regimen

Linperlisib: 80mg QD during the cycle 1-2，80mg QD for the first 7 days of cycle 3-6 (each cycle is 28 days) Cyclophosphamide: 50mg QD during the cycle 1-6 (each cycle is 28 days) Prednisone: 20mg QD during the cycle 1-6 (each cycle is 28 days) Thalidomide: 50mg QD during the cycle 1-6 (each cycle is 28 days) After six cycles, patients with CR or PR continue to receive linperlisib at a dose of 80mg for the first 7 days every cycle (each cycle is 28 days) until disease progression, intolerable toxicity, investigator judgment that treatment should be discontinued, or subject withdrawal of consent, whichever occurred first.

Intervention Type: DRUG

Linperlisib combined with CPT regimen

Linperlisib: 80mg QD during the cycle 1-2，80mg QD for the first 7 days of cycle 3-6 (each cycle is 28 days) Cyclophosphamide: 50mg QD during the cycle 1-6 (each cycle is 28 days) Prednisone: 20mg QD during the cycle 1-6 (each cycle is 28 days) Thalidomide: 50mg QD during the cycle 1-6 (each cycle is 28 days) After six cycles, patients with CR or PR continue to receive linperlisib at a dose of 80mg for the first 7 days every cycle (each cycle is 28 days) until disease progression, intolerable toxicity, investigator judgment that treatment should be discontinued, or subject withdrawal of consent, whichever occurred first.

Intervention Type: DRUG

Linperlisib combined with CPT regimen

Linperlisib: 80mg QD during the cycle 1-2，80mg QD for the first 7 days of cycle 3-6 (each cycle is 28 days) Cyclophosphamide: 50mg QD during the cycle 1-6 (each cycle is 28 days) Prednisone: 20mg QD during the cycle 1-6 (each cycle is 28 days) Thalidomide: 50mg QD during the cycle 1-6 (each cycle is 28 days) After six cycles, patients with CR or PR continue to receive linperlisib at a dose of 80mg for the first 7 days every cycle (each cycle is 28 days) until disease progression, intolerable toxicity, investigator judgment that treatment should be discontinued, or subject withdrawal of consent, whichever occurred first.

Intervention Type: DRUG

Linperlisib combined with CPT regimen

Linperlisib: 80mg QD during the cycle 1-2，80mg QD for the first 7 days of cycle 3-6 (each cycle is 28 days) Cyclophosphamide: 50mg QD during the cycle 1-6 (each cycle is 28 days) Prednisone: 20mg QD during the cycle 1-6 (each cycle is 28 days) Thalidomide: 50mg QD during the cycle 1-6 (each cycle is 28 days) After six cycles, patients with CR or PR continue to receive linperlisib at a dose of 80mg for the first 7 days every cycle (each cycle is 28 days) until disease progression, intolerable toxicity, investigator judgment that treatment should be discontinued, or subject withdrawal of consent, whichever occurred first.

Intervention Type: DRUG

Linperlisib combined with CPT regimen

Linperlisib: 80mg QD during the cycle 1-2，80mg QD for the first 7 days of cycle 3-6 (each cycle is 28 days) Cyclophosphamide: 50mg QD during the cycle 1-6 (each cycle is 28 days) Prednisone: 20mg QD during the cycle 1-6 (each cycle is 28 days) Thalidomide: 50mg QD during the cycle 1-6 (each cycle is 28 days) After six cycles, patients with CR or PR continue to receive linperlisib at a dose of 80mg for the first 7 days every cycle (each cycle is 28 days) until disease progression, intolerable toxicity, investigator judgment that treatment should be discontinued, or subject withdrawal of consent, whichever occurred first.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male or female, ≥18 years old;

2. Histologically confirmed diagnosis of FL/PTCL/NKTCL/CLL /MZL/MCL;

3. Except for CLL (using the 2018 iwCLL criteria), patients must have at least one measurable lesion/evaluable lesion that meets the 2014 version of Lugano lymphoma evaluation criteria;

4. FL patients:

Should be relapsed after second-line or more systemic therapy (CD20 monoclonal antibody and at least one alkylating agent, including but not limited to bendamustine, fludarabine, cyclophosphamide, isocyclophosphamide, etc.); 5. PTCL patients:

1. Have previously received at least one-line systemic treatment, have disease progression during or after the most recent treatment, or confirmed no objective response with adequate treatment;

2. Includes the following subtypes: PTCL-NOS, AITL, ALK+ALCL, ALK-ALCL，EATL; patients with ALCL must have previously received CD30-targeted therapy or be ineligible for CD30-targeted therapy; 6. NK/TCL patients:

1) Have previously received at least one line systemic treatment, have disease progression during or after the most recent treatment, or have confirmed no objective response with adequate treatment; 2) Have previously received a regimen containing Pegaspargase or L-Pegaspargase; 7. CLL patients:

1. Have measurable lesions (peripheral blood B lymphocytes ≥5×10^9/L, or enlarged lymph node (baseline LDi ≥ 1.5cm), or hepatomegaly or splenomegaly due to CLL);

2. Patients with resistance or intolerance following prior first-line or above therapy (regiments containing BTK inhibitors or BCL-2 inhibitors);

3. Treatment should be initiated when at least one indication for treatment according to IWCLL guideline are present; 8. MZL patients: Should have previously received at least two-line systemic therapy containing CD20 monoclonal antibodies and have not achieved at least partial response (PR) after recent systemic therapy, or have confirmed disease progression after treatment, and investigators judge that effective and standard treatment options are lacking; 9. MCL patients:

Previous second-line or higher treatment regimen including:

1. at least first-line immunotherapy or chemical immunotherapy containing anti-CD20 monoclonal antibody; Or anti-CD20 mab combined with BTK inhibitors;

2. have been treated with at least one appropriate BTK inhibitor and BCL-2 inhibitor (monotherapy or in combination with other antineoplastic agents); 10. ECOG PS: 0~2; 11. Expected survival ≥ 3 months; 12. Good organ function; 13. The washout period from the end of any previous antineoplastic therapy, including radiation therapy, chemotherapy, hormone therapy, surgery, or molecular-targeted therapy until participate in the trial should be at least 28 days or five half-life of the drug, whichever was shorter; 14. Fertile male and female subjects are willing to use effective contraceptive measures throughout the study period and for six months after the last dose; 15. Volunteer to participate in clinical studies and sign informed consent, willing to follow and able to complete all trial procedures.

Exclusion Criteria

Patients with any of the following conditions are not eligible to participate in this study:

1. Had been progressed on PI3K inhibitor before enrollment;

2. Any other anti-tumor therapy within 4 weeks;

3. The presence of third-space effusion (e.g., massive pleural effusion and ascites) that could not be controlled by drainage or other methods;

4. Involvement of the central nervous system (meninges or brain parenchyma);

5. Long-term use of corticosteroids exceeding 30mg/day of prednisone or its equivalent;

6. Inability to swallow, chronic diarrhea or intestinal obstruction, or other factors affecting drug intake and absorption;

7. Individuals with a history of allergies or known hypersensitivity to any component of the regimen;

8. A history of any cardiac disease, including: (1) angina; (2) arrhythmias requiring clinical intervention; (3) myocardial infarction; (4) heart failure; (5) any other cardiac conditions deemed unsuitable for participation in this trial by the investigator;

9. Active viral, bacterial, or fungal infections requiring treatment (such as pneumonia);

10. Uncontrolled diabetes, pulmonary fibrosis, acute lung disease, interstitial lung disease, or liver failure;

11. Individuals with HBV or HCV infection (defined as positive for HbsAg and/or HbcAb with detectable HBV DNA copies) or positive for active hepatitis C (HCV) antibodies;

12. A history of immunodeficiency, including positive HIV testing, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation, or a history of allogeneic bone marrow or hematopoietic stem cell transplantation;

13. Received autologous hematopoietic stem cell transplantation within 90 days prior to the first dose of study treatment;

14. Could not receive preventive treatment for pneumocystis, HSV, or HZV at screening;

15. Major surgery within 2 weeks before starting treatment;

16. Any adverse event related to prior treatment, but has not recovered to grade ≤ 1;

17. Existing active bleeding or new thrombotic disease, or have a history of bleeding tendency;

18. Pregnant or breastfeeding female patients, or women of childbearing potential with a positive baseline pregnancy test;

19. Concomitant diseases (such as severe hypertension, diabetes, thyroid disease, etc.);

20. Other malignancies within the last 5 years, except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix;

21. Received live attenuated vaccines within 30 days prior to the first dose;

22. Histologically or cytologically confirmed patients with grade 3b follicular lymphoma, and known follicular lymphoma transformed into diffuse large B-cell lymphoma;

23. T-cell lymphoma and NK/T-cell lymphoma with hemophagocytic syndrome;

24. Other situations deemed unsuitable for inclusion in the study by the researcher.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The First Affiliated Hospital with Nanjing Medical University

Nanjing, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Huayuan ZHU, MD, phD

Role: CONTACT

huayuan.zhu@hotmail.com

+86-13813810650

Facility Contacts

Huayuan ZHU, MD, phD

Role: primary

huayuan.zhu@hotmail.com

+86-13813810650

Other Identifiers

2024-SR-219

Identifier Type: -

Identifier Source: org_study_id