Dynamic CtDNA-guided Targeted Therapy in DLBCL

Phase 2

Not yet recruiting

• Conditions: Diffuse Large B Cell Lymphoma (DLBCL)
• Interventions: Drug: R-CHOP + X

• Registration Number: NCT06748521
• Lead Sponsor: Ruijin Hospital

Brief Summary

This is a prospective, single-arm, noninferiority trial involving patients with previously untreated CD20-positive DLBCL. The aim of this study is to determine the efficacy and safety of treatment stratified based on ctDNA dynamic changes after one cycle of chemotherapy and the targeted therapy based on DLBCL genotype.

A total of 108 patients were planned to be enrolled in this trial, and the patients were stratified according to the dynamic changes of ctDNA after one cycle of chemotherapy: the chemotherapy-sensitive group continued the original R-CHOP regimen, and the potential drug resistance group received genotype-guided targeted drug combination. The whole trial included a screening period (day -28 to day -1), a treatment period, and a 2-year follow-up period.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-12
• Study First Submitted: 2024-12-12
• Study First Submitted QC: 2024-12-22
• Last Update Submitted: 2024-12-22
• Study First Posted: 2024-12-27
• Last Update Posted: 2024-12-27
• Study Start: 2024-12-31
• Primary Completion: 2026-12-13
• Study Completion: 2028-06-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 108

Inclusion Criteria

• Signed Informed Consent Form
• Age 18-75 years at the time of signing Informed Consent Form and willingness to comply with study protocol procedures
• Previously untreated participants with CD20-positive DLBCL
• IPI score 2-5
• ECOG Performance Status of 0, 1, or 2
• Life expectancy ≥ 6 months

Exclusion Criteria

• Contraindication to any of the individual components of R-CHOP or Obutinib or Decitabine or Lenalidomide or Chidamide

• Have received systemic or local treatment including chemotherapy in the past

• Have received autologous stem cell transplantation in the past

• Past medical history of other malignant tumors, except basal cell carcinoma of the skin and cervical cancer in situ

• Accompanied by uncontrolled cardiovascular and cerebrovascular diseases, coagulopathy, connective tissue diseases, severe infectious diseases and other diseases

• Primary central nervous system lymphoma

• Left ventricular ejection fraction ≦50%

• Other concurrent and uncontrolled situation which will affect the patient's medical status based on researchers' decision

• Any of the following abnormal laboratory values (unless any of these abnormalities are due to underlying lymphoma):

  • ANC < 1.0 x 10^9/L
  • PLT < 75 x 10^9/L
  • Hb < 100g/L
  • Serum AST and ALT ≥ 2.5 x ULN
  • Total bilirubin ≥ 1.5 x ULN
  • Serum creatinine ≥ 1.5 x ULN

• Psychiatric patients or other patients who are known or suspected to be unable to fully accomplish with the research protocol

• Pregnant or lactating women

• Patients with positive HbsAg test results need to undergo HBV-DNA test and can be admitted to the group after turning negative. In addition, if the HBsAg test result is negative, but the HBcAb test is positive (regardless of the HBsAb status), HBV-DNA is also required；if the result is positive, patients also need to be treated to become negative before entering the group

• Patients living with HIV

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
treatment group	R-CHOP + X	-

Primary Outcome Measures

Name	Time	Method
Complete response (CR) rate	End of Cycle 6 (each cycle is 21 days)	CR rate at the end of treatment. Defined as the proportion of participants who achieved CR at the end of treatment.

Secondary Outcome Measures

Name	Time	Method
2-year progression-free survival (PFS) rate	2 years	PFS, defined as the time from enrollment to the first occurrence of disease progression or relapse using the 2014 Lugano Response Criteria or death due to any cause, whichever occurs first; as determined by the investigator. The 2-year PFS rate was the percentage of patients who did not experience disease progression or death within two years of enrollment.
2-year Overall survival (OS) rate	2 years	OS defined as the time from enrollment to death from any cause. The 2-year OS rate was the percentage of patients who did not die within two years of enrollment.
The incidence and severity of adverse events were determined according to the NCI CTCAE v5.0 rating scale	From enrollment to study completion, a maximum of 4 years	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. 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.