Linperlisib Combined With Chidamide in Patients With PTCL

Peripheral T-cell Lymphoma Clinical Trial

Official title:

PI3Kδ Inhibitor Linperlisib Combined With HDAC Inhibitor Chidamide Versus CHOP in Patients With Peripheral T-cell Lymphoma: a Multicenter, Open Label, Phase Ib/II Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06421948
• Other study ID #: HNSZLYYML08
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 1, 2024
• Est. completion date: May 31, 2026

Study information

• Verified date: May 2024
• Source: Henan Cancer Hospital
• Contact: Yanyan Liu
• Phone: 86 037165587791
• Email: yyliu[@]zzu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to determine the maximum tolerated dose (MTD) of PI3Kδ inhibitor linperlisib when combined with fixed dose of HDAC inhibitor chidamide in participants with peripheral T-cell lymphoma (PTCL), and to compare the combination of linperlisib and chidamide to standard CHOP (cyclophosphamide, doxorubicin/epirubicin, vincristine, and prednisone) regimen chemotherapy in the frontline treatment of PTCL to see which therapy is better.

Description:

In the phase Ib trial, participants with newly diagnosed or relapsed/refractory PTCL will receive fixed dose of chidamide (20 mg, twice a week) and escalating dose of linperlisib (40 mg, 60 mg, or 80 mg, once a day), to find out the optimal dose of linperlisib.

In the phase II trial, participants with newly diagnosed PTCL will be randomized into experimental arm (arm A) to receive linperlisib in combination with chidamide, or control arm (arm B) to receive standard CHOP regimen chemotherapy.

Interim efficacy assessment will be performed after three cycles of treatment. Responded participants will receive another three cycles of treatment. After a total of 6 cycles of treatment, participants can choose autologous hematopoietic stem cell transplantation, maintenance treatment with linperlisib and/or chidamide, or watch and wait.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: May 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Age 18-75 years at the time of inclusion (Age 18-80 years for phase Ib study)

• Patients with a newly diagnosed and histologically confirmed PTCL (phase Ib study includes both newly diagnosed and relapsed/refractory PTCL). Anaplastic large cell lymphoma and NK/T-cell lymphoma are not included.

• ECOG PS 0-2 at protocol entry

• Estimated life expectancy of 6 months or longer

• Measurable disease

• Hemoglobin = 8 g/dL (=5 mmol/l); Platelets = 75 x 10E9/L; Absolute neutrophil count = 1.0 x 10E9/L; Platelets = 50 x 10E9/L permitted if documented bone marrow involvement; Serum bilirubin = 1.5 x upper limit of normal (ULN); Serum glutamic-oxaloacetic transaminase (AST) and/or serum glutamic-pyruvic transaminase (ALT) = 2.5 x ULN, or = 5 x ULN if elevation is due to hepatic involvement by lymphoma; Serum creatinine = 1.5 x ULNb; left ventricular ejection fraction (LVEF) = 50%

• Women of childbearing potential must use safe anticonception (e.g. contraceptive pills, intrauterine devices etc.) during the study and 12 months after the last administration of study drugs; Male patients must use contraception for the duration of the study and 6 months after the last administration of study drugs if his partner is of childbearing potential

• Written informed consent

Exclusion Criteria:

• Patients previously treated with PI3K inhibitor

• Patients previously treated with chidamide (phase Ib study is not limited by this item)

• Suspected or documented central nervous system involvement by lymphoma

• Patients with positive HIV and/or active hepatitis B and/or hepatitis C infection

• Patients with active, uncontrolled infections

• Unwillingness or inability to comply with the protocol

• Deemed 'unfit' by the treating physician

• Pregnant and/or breastfeeding women

• Concurrent severe and/or uncontrolled medical disease which is not lymphoma-related

• Patients with contraindications to chemotherapy

• Known hypersensitivity to one or more of the study drugs

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• Peripheral T-cell Lymphoma

Intervention

Drug:
• Linperlisib and chidamide
A combination of linperlisib and chidamide will be administered for 6 cycles in patients responded to treatment.
• cyclophosphamide, doxorubicin/epirubicin, vincristine, and prednisone
A combination of cyclophosphamide, doxorubicin/epirubicin, vincristine, and prednisone (CHOP) will be administered for 6 cycles in patients responded to treatment.

Locations

Country	Name	City	State
China	Affiliated Cancer Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Yanyan Liu

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CRR	Complete response rate	Through study completion, an average of 3 years
Secondary	PFS	Progression-free survival	12 months
Secondary	OS	Overall survival	12 months
Secondary	AE	Adverse event	Through study completion, an average of 3 years