Linperlisib Combined With Chidamide in Patients With PTCL

Yanyan Liu

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

Peripheral T-cell Lymphoma

Treatments

Drug: cyclophosphamide, doxorubicin/epirubicin, vincristine, and prednisone

Drug: Linperlisib and chidamide

Study type

Interventional

Funder types

Other

Identifiers

NCT06421948

HNSZLYYML08

Details and patient eligibility

About

The phase Ib part of this study aims to determine the recommended phase II dose （RP2D）of linperlisib in combination with chidamide for the treatment of peripheral T-cell lymphoma (PTCL).

The phase IIa part is designed to evaluate the preliminary efficacy and safety of the linperlisib plus chidamide regimen in newly diagnosed PTCL patients.

The phase IIb part compares the efficacy and safety of linperlisib combined with chidamide versus the standard CHOP (CHOP-like) regimen in newly diagnosed PTCL patients.

Full 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 RP2D.

The phase IIa study is an exploratory efficacy study enrolling newly diagnosed PTCL patients who receive linperlisib in combination with chidamide to evaluate the efficacy and safety of the regimen.

In the phase IIb study, 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 (or CHOP-like) 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.

Enrollment

134 estimated patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age 18-75 years at the time of inclusion (Age 18-80 years for phase Ib and IIa 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, NK/T-cell lymphoma, and primary cutaneous 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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

134 participants in 4 patient groups

Phase Ib: Dose-escalation cohort

Experimental group

Description:

Linperlisib was administered in three dose groups of 40 mg, 60 mg, and 80 mg once daily (QD), with each group enrolling 3-6 patients with newly diagnosed or relapsed/refractory PTCL. Chidamide was given at a fixed dose of 20 mg twice weekly. During the 21-day DLT (dose-limiting toxicity) observation period, the maximum tolerated dose (MTD) of linperlisib was assessed, and the recommended phase II dose (RP2D) was determined for use in the phase II study.

Treatment:

Drug: Linperlisib and chidamide

Phase IIa: Expansion cohort

Experimental group

Description:

In newly diagnosed PTCL patients, the efficacy and safety of Linperlisib (RP2D) combined with Chidamide were evaluated. Each treatment cycle is 3 weeks, and patients who responded effectively would receive a total of six cycles of therapy.

Treatment:

Drug: Linperlisib and chidamide

Phase IIb: Randomized controlled study: experimental arm

Experimental group

Description:

Patients randomized to the experimental group will receive combination therapy with Linperlisib and Chidamide.

Treatment:

Drug: Linperlisib and chidamide

Phase IIb: Randomized controlled study: Control arm

Active Comparator group

Description:

Patients randomized to the control group will receive conventional CHOP or CHOP-like regimen chemotherapy.