Chidamide in Combination With Decitabine in Non-Hodgkin's Lymphoma Relapsed After Chimeric Antigen Receptor

Study Overview
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Brief Summary
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This is a Phase I/II clinical trial for patients with r/r Non-Hodgkin's Lymphoma relapsed after chimeric antigen receptor T cells infusion. The purpose is to evaluate the safety and efficacy of the treatment with chidamide in combination with decitabine.

Official Title
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Chidamide in Combination With Decitabine in Non-Hodgkin's Lymphoma Relapsed After Chimeric Antigen Receptor : An Open-label Phase I/II Trial

Conditions
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Non Hodgkin Lymphoma

Intervention / Treatment
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* Drug: Chidamide
* Drug: Decitabine
* Drug: Camrelizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have histological confirmation of Non-Hodgkin lymphoma (NHL) and relapsed after chimeric antigen receptor T cells infusion. 18 to 65 years of age. ECOG performance of less than 2. Life expectancy of at least 3 months. Subjects with lymphoma must have at least one measureable new lesion >1.5cm as defined by lymphoma response criteria. Subjects must have relapsed after chimeric antigen receptor T cells infusion without any intervention treatment prior to Day 1. Subjects must have adequate marrow, live, renal and heart functions. Exclusion Criteria: Subjects with any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications. Serious uncontrolled medical disorders or active infections, pulmonary infection especially. Active alimentary tract hemorrhage or history of alimentary tract hemorrhage in one month . Prior organ allograft. Women who are pregnant or breastfeeding. Women with a positive pregnancy test on enrollment or prior to investigational product administration. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: chidamide in combination with decitabine<br>chidamide 10mg/day, days 1-5, 20mg/day, day 8, 11,15, 18; decitabine 10 mg/day, days 1-5, every 3 weeks | Drug: Chidamide<br>* Chidamide is a novel and orally active benzamide class of HDAC inhibitor that selectively inhibits activity of HDAC1, 2, 3 and 10, which can Induce tumor-cell apoptosis, suppress cell proliferation and enhance immune surveillance; Decitabine is an investigational (experimental) drug that works by depleting DNA methyltransferase 1(DNMT1), which can increase tumor antigens and HLA expression, enhances antigen processing, promotes T cell infiltration, and boosts effector T cell function.<br>Drug: Decitabine<br>* Decitabine is an investigational (experimental) drug that works by depleting DNA methyltransferase 1(DNMT1), which can increase tumor antigens and HLA expression, enhances antigen processing, promotes T cell infiltration, and boosts effector T cell function.<br>|
| Experimental: decitabine in combination with Camrelizumab<br>decitabine 10 mg/day, days 1-5, every 3 weeks; camrelizumab 200mg d6 | Drug: Decitabine<br>* Decitabine is an investigational (experimental) drug that works by depleting DNA methyltransferase 1(DNMT1), which can increase tumor antigens and HLA expression, enhances antigen processing, promotes T cell infiltration, and boosts effector T cell function.<br>Drug: Camrelizumab<br>* Camrelizumab is a humanized anti-PD-1 monoclonal antibody.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CR rate | CR rate assess by investigators per the 2014 Lugano classification rate of subjects achieved complete response in all evaluable subjects | 2 years | 
| Adverse events | Adverse events were defined according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0) | 2 years |