Linperlisib plus CPT (cyclophosphamide, prednisone, thalidomide) for relapsed or refractory non-Hodgkin lymphoma

A Multicenter Prospective Study of Linperlisib Combination With Cyclophosphamide, Prednisone, and Thalidomide (CPT) in Relapsed and/or Refractory Non-Hodgkin Lymphoma

This trial tests whether adding linperlisib to a CPT regimen helps adults with relapsed or refractory non-Hodgkin lymphoma.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 180 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The First Affiliated Hospital with Nanjing Medical University (other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, cyclophosphamide, fludarabine, prednisone
• Locations: 1 site (Nanjing, Jiangsu)
• Trial ID: NCT07195799 on ClinicalTrials.gov

What this trial studies

This is a multicenter, open-label, non-randomized Phase 2 trial using multiple cohorts to give linperlisib together with a cyclophosphamide‑prednisone‑thalidomide (CPT) backbone to patients with various relapsed or refractory NHL subtypes. The trial enrolls adults with histologically confirmed FL, PTCL, NKTCL, CLL, MZL, or MCL who meet prior-therapy and measurable-disease requirements for their subtype. Primary objectives are to measure anti-lymphoma activity (for example response rate and progression-free survival) and to characterize safety and tolerability of the combination. Dosing details and cohort-specific eligibility determine treatment schedules and monitoring at the participating site.

Who should consider this trial

Good fit: Adults (≥18 years) with histologically confirmed relapsed or refractory FL, PTCL, NKTCL, CLL, MZL, or MCL who meet subtype-specific prior therapy and measurable-disease criteria (for example FL after ≥2 systemic lines, PTCL after ≥1 prior systemic therapy) are the intended candidates.

Not a fit: Patients who are newly diagnosed, who cannot tolerate the study drugs because of comorbidities or organ dysfunction, or who do not meet the cohort-specific prior‑therapy or measurable-disease requirements are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the combination could increase response rates or extend disease control for patients with relapsed or refractory NHL who have limited treatment options.

How similar studies have performed: PI3K inhibitors like linperlisib have shown activity in some NHL subtypes but have had mixed safety and durability profiles, and combining a PI3K inhibitor with a CPT regimen is a relatively novel approach with limited prior data.

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.

Where this trial is running

Nanjing, Jiangsu

• The First Affiliated Hospital with Nanjing Medical University — Nanjing, Jiangsu, China (RECRUITING)

Study contacts

• Study coordinator: Huayuan ZHU, MD, phD

Conditions: Non-Hodgkin Lymphoma