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This open-label, multi-cohorts, phase 1/2 study has the primary objective of comparing decitabine-primed tandem CART 19/20 solo, with decitabine-primed tandem CART 19/20 plus chidamide, decitabine-primed tandem CART 19/20 plus decitabine, and decitabine-primed tandem CART 19/20 plus decitabine+chidamide in patients with aggressive B-NHL who were confirmed as Relapsed and/or Refractory B cell Non-Hodgkin's Lymphoma with hugh tumor burden (Sum of the Product of the perpendicular Diameters for multiple lesions, SPD ≥ 100cm^2 or the largest-diameter of tumor ≥ 10 cm.).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Decitabine-primed Tandem CAR19/20 engineered T cells | Active Comparator | Tandem dual Specificity targeting CD19 and CD20 decitabine-primed CAR-T cells can recognize and kill the CD19 negative malignant cells through recognition of CD20 and improve the possibility of killing lymphoma tumor cells. |
|
| Decitabine-primed Tandem CAR19/20 engineered T cells plus chidamide | Experimental | 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-primed Tandem CAR19/20 engineered T cells plus decitabine | Experimental | 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. |
|
| Decitabine-primed Tandem CAR19/20 engineered T cells plus chidamide+decitabine | Experimental | The combination of chidamide and decitabine can increase tumor antigens and HLA expression, enhances antigen processing, promotes T cell infiltration, and boosts effector T cell function, induce tumor-cell apoptosis, suppress cell proliferation and enhance immune surveillance |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Chidamide | Drug | Chidamide will be added 1 month after responding to CART cells infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Adverse events after intervention | Safety Outcome | 12 months |
| Progression Free Survival | 2 years | |
| Duration of Response | 2 years | |
| Overall Survival | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate Outcome Measure | ORR assess by investigators per the 2014 Lugano classification rate of subjects achieved objective response in all evaluable subjects | 2 years |
| Intervention treatment-related adverse events (AEs) |
| Measure | Description | Time Frame |
|---|---|---|
| Exploratory research | Track cart cells in PB after infusions by TCR, transcriptional, and epigenetic sequencing. | 12 months |
Inclusion Criteria:
Age ≥16 and ≤ 65 years.
Sum of the Product of the perpendicular Diameters for multiple lesions, SPD ≥ 100cm^2 or the largest-diameter of tumor ≥ 10cm.
Histologically confirmed CD20+ and/or CD19+ aggressive B-cell non-Hodgkin lymphoma (NHL), including the following types defined by the World Health Organization (WHO) 2016:
Refractory disease or relapse after treatment with ≥2 lines of chemotherapy, including rituximab and anthracycline and either having failed autologous hematopoietic stem cell transplantation (HSCT), being ineligible for autologous HSCT or not consenting to autologous HSCT.
We defined chemotherapy-refractory disease as meeting one or more of the following criteria:
Failure following autologous HSCT was defined as follows:
PD or relapse ≥3 months after treatment with targeted CD19 therapy, including CD19 CAR T cells or anti-CD19/anti-CD3.
Successful leukapheresis assessment and preculture of T cells.
Life expectancy > 3 months.
Adequate organ function:
An adequate bone marrow reserve defined as:
Measurable or assessable disease according to the "IWG Response Criteria for Malignant Lymphoma" (Cheson 2014). Patients in complete remission (CR) with no evidence of disease were not eligible.
Informed consent/assent requiring that all patients have the ability to understand and the willingness to provide written informed consent.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Weidong Han, M.D. | Contact | +861055499341 | hanwdrsw@sina.com |
| Name | Affiliation | Role |
|---|---|---|
| Weidong Han, M.D. | Chinese PLA Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Biotherapeutic Department of Chinese PLA General Hospital | Recruiting | Beijing | Beijing Municipality | 100853 | China |
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| Decitabine | Drug | Decitabine will be added 1 month after responding to CART cells infusion |
|
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| Chidamide and Decitabine | Drug | Both chidamide and decitabine will be added 1 month after responding to CART cells infusion |
|
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| Decitabine-primed Tandem CAR19/20 engineered T cells | Biological | Tandem CAR19/20 engineered T cells |
|
|
Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0
| 12 months |
| ID | Term |
|---|---|
| C547816 | N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide |
| C423142 | KPNA1 protein, human |
| 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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