Diffuse Large B-Cell Lymphoma
Conditions
Keywords
Chidamide, Tucidinostat, Minimal Residual Disease, Maintenance Therapy, Double-Expressor Lymphoma
Brief summary
This is a prospective, multicenter, single-arm, open-label phase 2 study designed to evaluate the efficacy and safety of chidamide maintenance in adults with newly diagnosed double-expressor diffuse large B-cell lymphoma (DLBCL) who achieve complete response after induction therapy but remain ctDNA minimal residual disease (MRD)-positive. Eligible participants will receive oral chidamide 20 mg on Days 1, 4, 8, and 11 of each 21-day cycle. ctDNA MRD will be assessed every 12 weeks. Treatment will continue until two consecutive MRD-negative assessments, disease progression, intolerable toxicity, withdrawal of consent, or completion of 2 years of maintenance. The primary objectives are to evaluate ctDNA MRD negativity and 2-year progression-free survival. Secondary objectives include event-free survival, overall survival, and safety.
Detailed description
Patients with double-expressor DLBCL remain at increased risk of relapse despite achieving complete response after induction therapy. ctDNA-based MRD assessment may identify a subgroup with persistent molecular disease who are at particularly high risk for recurrence. Chidamide is an oral selective histone deacetylase inhibitor with potential antitumor and immune-modulating activity in B-cell lymphomas. This prospective, multicenter, single-arm, open-label phase 2 study will enroll adult patients with newly diagnosed CD20-positive double-expressor DLBCL, defined by MYC expression \>=40% and BCL2 expression \>=50% by immunohistochemistry, who achieve complete response after initial induction therapy but remain ctDNA MRD-positive. Participants will receive chidamide 20 mg orally on Days 1, 4, 8, and 11 of each 21-day cycle. ctDNA MRD will be monitored every 12 weeks. Treatment will stop upon two consecutive MRD-negative assessments, disease progression, intolerable toxicity, withdrawal of consent, or completion of 2 years of maintenance. The study will evaluate ctDNA MRD negativity rate and 2-year progression-free survival as primary endpoints, with event-free survival, overall survival, and safety as secondary endpoints.
Interventions
DRUGChidamide
Chidamide 20 mg orally on Days 1, 4, 8, and 11 of each 21-day cycle. ctDNA MRD assessments will be performed every 12 weeks. Treatment will continue until two consecutive MRD-negative assessments at least 3 months apart, disease progression, intolerable toxicity, withdrawal of consent, or completion of 2 years of maintenance.
Sponsors
Rong Tao
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed diffuse large B-cell lymphoma, CD20-positive. * Double-expressor lymphoma confirmed by pathology, defined as MYC expression \>=40% and BCL2 expression \>=50% by immunohistochemistry. * Complete response after initial induction therapy. * Age \>=18 and \<=80 years. * ECOG performance status 0-2. * No prior history of malignant tumor and no concurrent malignancy. * International Prognostic Index (IPI) score \>1. * ctDNA MRD-positive at screening/enrollment. * Life expectancy of at least 6 months, in the opinion of the investigator. * Written informed consent provided before any study-specific procedure.
Exclusion criteria
* Failure to achieve complete response after initial induction therapy. * Prior organ transplantation. * Uncontrolled coagulopathy or active bleeding. * Uncontrolled cardiovascular or cerebrovascular disease, including left ventricular ejection fraction \<50%, connective tissue disease, or severe active infection. * Major organ surgery within 6 weeks before screening. * Screening laboratory abnormalities not attributable to lymphoma, including: neutrophil count \<1.5 x 10\^9/L; platelet count \<80 x 10\^9/L (or \<50 x 10\^9/L in patients with bone marrow involvement); total bilirubin \>1.5 x upper limit of normal; ALT/AST \>2.5 x upper limit of normal, or \>5 x upper limit of normal in patients with hepatic involvement; serum creatinine \>1.5 x upper limit of normal. * Active hepatitis B not meeting protocol-defined virologic criteria for enrollment; patients with positive HBsAg or positive HBcAb require HBV DNA testing and must meet protocol-specified thresholds. * HIV infection. * Ongoing antitumor therapy for lymphoma or another malignancy. * Drug abuse or chronic alcohol abuse that may interfere with study evaluation. * Psychiatric illness or any condition resulting in inability to comply with the protocol. * Requirement for ongoing treatment with strong or moderate CYP3A inhibitors or inducers; patients exposed to these agents within 7 days before first study dose, or within fewer than 5 half-lives, are not eligible. * Inability to swallow capsules or clinically significant gastrointestinal disorders that may affect drug absorption, including malabsorption syndrome, bariatric surgery, inflammatory bowel disease, or partial/complete bowel obstruction. * Any other uncontrolled medical condition that, in the investigator's judgment, may compromise safety, interfere with oral drug absorption or metabolism, or place the participant at excessive risk.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ctDNA MRD Negativity Rate | From first dose up to 24 months | The proportion of enrolled participants who convert from ctDNA MRD-positive status at study entry to ctDNA MRD-negative status during chidamide maintenance, based on the protocol-specified ctDNA assay. |
| 2-Year Progression-Free Survival Rate | 24 months after study entry | The proportion of enrolled participants who are alive and free of disease progression 24 months after study entry. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event-Free Survival | From study entry up to 24 months | Time from study entry to disease progression, initiation of new antitumor therapy, or death from any cause. |
| Overall Survival | From study entry up to 24 months | Time from study entry to death from any cause. |
| Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events | From first dose to 30 days after last dose. | Incidence of hematologic and non-hematologic adverse events and serious adverse events, graded according to NCI CTCAE version 5.0. |
Countries
China
Contacts
CONTACTRong Tao, MD & PhD
CONTACTWenhao Zhang, MD
STUDY_CHAIRRong Tao, MD & PhD
Fudan University
PRINCIPAL_INVESTIGATORWenhao Zhang, MD
Fudan University
Outcome results
None listed