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This phase I/II trial aims to evaluate safety and efficacy of Chidamide, Decitabine and Immune checkpoint inhibitors in relapsed/refractory Non-Hodgkin Lymphoma and advanced solid tumors.
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. Low-dose decitabine inhibits the activity of DNA methyltransferase, which can increase the expression of tumor antigens and HLA molecules, enhance antigen processing, promote T cell infiltration, and boost effector T cell function. Immune checkpoint inhibitors (ICIs) have emerged as effective therapies for many cancers by promoting the reactivation and restoring function of T cells. In conclusion, we speculate that the chemotherapy free regimen of Chidamide, Decitabine and Immune checkpoint inhibitors may explore a new avenue for therapeutic intervention in relapsed/refractory Non-Hodgkin Lymphoma and advanced solid tumors.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental arm | Experimental | Drug: Chidamide10mg/day, day1-4; 20mg/day, day8, 11, 15, 18. Drug: Decitabine10mg/day, day1-5. Drug: Immune Checkpoint Inhibitors(anti-PD1/PD-L1/CTLA4 antibodies). Physicians will decide which ICIs will be used during treatment. Every 3 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Chidamide | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Objective response rate (ORR) | The percentage of patients with CR or PR was determined according to the revised lymphoma efficacy evaluation criteria (Lugano 2014 criteria) and Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). | 3 years |
| Adverse events | Incidence, nature, and severity of adverse events are graded according to the National Cancer Institute Common Terminology Criteria for adverse events (version5.0). | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Duration of response (DOR) | Time from the first recording of CR or PR evidence to disease progression or death from any cause was determined according to the revised lymphoma efficacy evaluation criteria (Lugano 2014 criteria) and Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Biomarkers predictive of response | Biomarkers from tumor cells, lymphocytes and tumor microenvironment will be assessed for their potential in predicting clinical response. | 3 years |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Weidong Han, Professor | Contact | +86-10-55499341 | hanwdrsw@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Weidong Han, Prfessor | Biotherapeutic Department, Chinese PLA General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Biotherapeutic Department, Chinese PLA General Hospital | Recruiting | Beijing | Beijing Municipality | 100853 | China |
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| Decitabine | Drug | Low-dose decitabine inhibits the activity of DNA methyltransferase, which can increase tumor antigens and HLA expression, enhance antigen processing, promote T cell infiltration, and boost effector T cell function. |
|
| Immune checkpoint inhibitors(anti-PD1/PD-L1/CTLA4 antibodies) | Drug | Immune checkpoint inhibitors (ICIs) have emerged as effective therapies for many cancers by promoting the reactivation and restoring function of T cells. |
|
| Progression-free survival (PFS) |
Time from the date of first administration of the study drug to disease progression or death from any cause. |
| 3 years |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C547816 | N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide |
| D000077209 | Decitabine |
| ID | Term |
|---|---|
| D001374 | Azacitidine |
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
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