Diffuse Large B-Cell Lymphoma (DLBCL)
Conditions
Keywords
newly diagnosed MYC/BCL2 double-expressor DLBCL
Brief summary
Efficacy and safety of chidamide in combination with the R-mini CHOP regimen, followed by chidamide plus CD20 monoclonal antibody as maintenance therapy, in elderly patients with newly diagnosed MYC/BCL2 double-expressor DLBCL.
Detailed description
The primary study objective is to evaluate the 2-year progression-free survival (PFS) rate of chidamide in combination with the R-miniCHOP regimen. Secondary objectives include the objective response rate (ORR), duration of response (DOR), complete response (CR) rate, the percentage of patients converting from PR/SD to CR/PR, overall survival (OS), and safety parameters. The exploratory objective is to investigate the correlation between biomarkers (e.g., tumor genomics, proteomics) and ctDNA with treatment efficacy.
Interventions
DRUGChidamide
Chidamide, oral, 20 mg (4 tablets) each time, twice a week, D1-14.
DRUGRituximab
Rituximab, 375 mg/m² IV, Cycle 1-4, Day 1.
DRUGCyclophosphamide
Cyclophosphamide, 400 mg/m² IV, Cycle 1-4, Day 2.
DRUGDoxorubicin
Doxorubicin, 25 mg/m² IV, Cycle 1-4, Day 2.
DRUGVincristine
Vincristine, 1 mg/m² IV, Cycle 1-4, Day 2.
DRUGPrednisone
Prednisone, 40 mg/m² orally, Cycle 1-4, Days 1-5.
DRUGChidamide + Rituximab maintenance
Chidamide, oral, 20 mg (4 tablets) each time, twice a week, D1-14. Rituximab, 375 mg/m² IV, once every 12 weeks. 21 days/cycle.
Sponsors
Ou Bai, MD/PHD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 70 years; 2. No prior treatment for DLBCL; 3. Histopathologically confirmed diagnosis (all of the following conditions must be met simultaneously): ① Diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), and CD20-positive; ② "MYC/BCL2 double-expressor": Immunohistochemistry (IHC) per WHO criteria: MYC ≥ 40%, and BCL2 ≥ 50%; ③ Non-"double-hit" or "triple-hit" lymphoma; 4. At least one 18F-fluorodeoxyglucose (18FDG)-avid lesion on positron emission tomography-computed tomography (PET-CT) according to the 2014 Lugano classification for Hodgkin and non-Hodgkin lymphoma; 5. International Prognostic Index (IPI) score \> 1; 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2; 7. At screening, laboratory tests must meet the following criteria, unless judged by the investigator to be due to lymphoma (no corrective or supportive treatment for the indicators below within 2 weeks prior to assessment): ① Hematology: Hemoglobin (Hb) ≥ 90 g/L, Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L, Platelet count (PLT) ≥ 90 × 10⁹/L; ② Biochemistry: Serum creatinine (Cr) ≤ 1.5 × upper limit of normal (ULN); Total bilirubin (TBIL) ≤ 1.5 × ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN (≤ 5 × ULN in cases of liver metastasis); 8. Life expectancy ≥ 6 months; 9. Understand and voluntarily sign a written informed consent form.
Exclusion criteria
1. Central nervous system (CNS) involvement; 2. Transformed lymphoma, i.e., lymphoma transformed from other lymphoma types such as follicular lymphoma, marginal zone B-cell lymphoma, or chronic lymphocytic leukemia/small lymphocytic lymphoma; specific subtypes of DLBCL (e.g., primary CNS DLBCL, etc.); 3. Uncontrolled cardiovascular or cerebrovascular diseases, coagulation disorders, autoimmune diseases, or severe infectious diseases; 4. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, or known sensitivity or allergic reactions to murine products; contraindications to any component of the CHOP regimen or chidamide; 5. HIV/HCV infection; 6. If HBsAg is positive, HBV DNA testing is required; patients with negative DNA may be enrolled. If HBsAg is negative but HBcAb is positive (regardless of HBsAb status), HBV DNA testing is required; patients with negative DNA may be enrolled. 7. Uncontrolled cardiovascular or cerebrovascular diseases, coagulation disorders, autoimmune diseases, or severe infectious diseases; 8. Inability to comply with the study protocol due to psychiatric or other unknown reasons; 9. For female patients of childbearing potential or male patients with partners of childbearing potential, unwillingness or inability to use effective contraception throughout the study treatment period and for 12 weeks after the last dose of chidamide or 12 months after the last dose of rituximab, whichever is longer; pregnant or breastfeeding women; 10. Other conditions deemed unsuitable for participation in this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | 24 months | The time from study enrollment to the first documented disease progression or death from any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | 24 months | To assess the Overall Response Rate (ORR) referred to Lugano 2014. |
| Duration of Response (DOR) | 24 months | The duration from the first documentation of response (achievement of complete response or partial response) to the first unequivocal evidence of relapse or progression. |
| Complete Response Rate (CRR) | 24 months | To assess the Complete Response Rate (CRR) referred to Lugano 2014. |
| Percentage of patients converting from PR/SD to CR/PR | 24 months | Percentage of patients converting from PR/SD to CR/PR |
| Overall survival（OS） | 24 months | Overall survival（OS） is defined as the time from the date of enrollment to the date of death from any cause. |
| Adverse Events | 24 months | An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment, assessed by NCI-CTCAE v5.0. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. |
Countries
China
Contacts
CONTACTOu Bai, PHD
PRINCIPAL_INVESTIGATOROu Bai, PHD
The First Bethune Hospital of Jilin University
Outcome results
None listed