PI3Kδ Inhibitor Parsaclisib Combined With Chidamide for the Treatment of Relapsed/Refractory Peripheral T-cell Lymphoma

Study Overview
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Brief Summary
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This is a prospective single-arm, single-center, phase Ib/II clinical trial of PI3Kδ inhibitor Parsaclisib combined with chidamide for the treatment of relapsed/refractory peripheral T-cell lymphoma.

Official Title
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A Single Arm, Single-center, Phase Ib/II Clinical Trial of PI3Kδ Inhibitor Parsaclisib Combined With Chidamide for the Treatment of Relapsed/Refractory Peripheral T-cell Lymphoma

Conditions
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Peripheral T-Cell Lymphoma

Intervention / Treatment
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* Drug: Parsaclisib
* Drug: Chidamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 to 75 years old (including 18 and 75) Agreeing to sign the written informed consents Diagnosed as peripheral T-cell lymphoma, including peripheral T-cell lymphoma, unspecified type, anaplastic large cell lymphoma (ALK negative or positive), angioimmunoblastic T-cell lymphoma, enteropathy Related T-cell lymphoma, hepatosplenic T-cell lymphoma, γ/δ T-cell lymphoma, NK/T-cell lymphoma, and other subtypes of PTCL that the investigator judges to be suitable for participating in this study Received at least first-line anti-tumor therapy in the past, whether or not Chidamide has been used Having at least one measurable lesions World health organization-Eastern Cooperative Oncology Group Performance Status (ECOG) 0-2 Life expectancy no less than 3 months enough main organ function Pregnancy test within 7 days must be negative for women of childbearing period, and appropriate measures should be taken for contraception for women in childbearing period during the study and six months after this study Agreeing to follow the trail protocol requirements Exclusion Criteria: Types other than peripheral T-cell lymphoma listed in the enrollment criteria Diagnosed as central nervous system lymphoma Received palliative treatment for other malignant tumors in the past 2 years Uncontrolled active infection Congestive heart failure, uncontrolled coronary heart disease, arrhythmia and heart infarction less than 6 months The non-hematological toxicity caused by the previous anti-tumor treatment has not recovered to ≤1 grade, and the hematological toxicity has not recovered to ≤2 grade Patients with a history of mental illness Those who are known to be allergic to the active ingredients or excipients of the drug parsaclisib and chidamide Received PI3Kδ inhibitor treatment in the past Received autologous hematopoietic or allogeneic hematopoietic stem cell transplantation within 3 months World health organization-Eastern Cooperative Oncology Group Performance Status (ECOG) >2 There are factors that affect the absorption of oral drugs Pregnant or lactating women Researchers determine unsuited to participate in this trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PI3Kδ inhibitor Parsaclisib plus Chidamide<br>Phase Ib (Explored the appropriate dose of Parsaclisib in combination with chidamide) Parsaclisib is taken orally every day continuously, at approximately the same time every day, without food restriction, once a day. Chidamide is taken fixed 20mg twice a week with an interval of no less than 3 days, and taken 30 minutes after breakfast. Phase II: Induced treatment: Received the initial dose of Parsaclisib determined in Phase Ib within the first 8 weeks. Maintain treatment: 2.5mg orally every day continuously, at approximately the same time every day, without food restriction, once a day. Chidamide is taken fixed 20mg twice a week with an interval of no less than 3 days, and taken 30 minutes after breakfast. | Drug: Parsaclisib<br>* Phase Ib: Parsaclisib is taken orally every day continuously, at approximately the same time every day, without food restriction, once a day. This stage follows the traditional 3+3 model. Parsaclisib is set at 10 mg/day, 15 mg/day, 20 mg/day 3 dose groups, starting from 10 mg/day, each group included 3 subjects. The final dose determined at this stage will be used in the Phase II study. Phase II: Induced treatment: Received the initial dose of Parsaclisib determined in Phase Ib within the first 8 weeks (including the treatment received in Phase Ib). Maintain treatment: 2.5mg orally every day continuously, at approximately the same time every day, without food restriction, once a day until disease progression, death or unacceptable toxicity developments. The maximum treatment time of Parsaclisib is no more than 2 years.<br>* Other names: PI3K inhibitor;Drug: Chidamide<br>* Phase Ib: Chidamide is taken fixed 20mg twice a week with an interval of no less than 3 days, and taken 30 minutes after breakfast. Phase II: Chidamide is taken fixed 20mg twice a week with an interval of no less than 3 days, and taken 30 minutes after breakfast until disease progression, death or unacceptable toxicity developments.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate | the total proportion of patients with complete response (CR) and partial response (PR) | every 8 or 12 weeks from the day of the first cycle to 2 years after the last patient's enrollment (each cycle is 28 days). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year progression-free survival | the total proportion of patients with no progression from date of the first day of treatment to the date of confirmed progressive disease or death which one occurs first | from the day of the first cycle of treatment to the date of confirmed progressive disease or death, whichever occurs first, up to 2 years after last patient's enrollment (each cycle is 28 days). | 
| 2-year overall survival | from date of first day of treatment to the date of death by any cause | from date of the first cycle of treatment to the date of death from any cause, assessed up to 2 years after last patient's enrollment (each cycle is 28 days). | 
| incidence and relationship with study drugs of grade 3-4 adverse events | the incidence and relationship with study drugs of grade 3 or 4 adverse events (based on NCI CTC-AE v4.03 | from the date of the first cycle of treatment to 2 years after last patient's enrollment (each cycle is 28 days). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsed/Refractory Peripheral T-cell Lymphoma, PI3Kδ inhibitor, Chidamide