Dynamic CtDNA-guided Targeted Therapy in DLBCL

Efficacy and Safety of Dynamic CtDNA-guided Targeted Therapy in Patients with Previously Untreated Diffuse Large B-cell Lymphoma

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Diffuse Large B Cell Lymphoma (DLBCL)
• Intervention / Treatment: Drug: R-CHOP + X

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Weili Zhao, MD, PhD; Phone Number: 610707 +862164370045; Email: zhao.weili@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: treatment group

Drug: R-CHOP + X; Eligible participants will receive 1 cycle of R-CHOP therapy with genotyping and ctDNA testing at C1D14. Chemotherapy sensitive patients with C1D14 ctDNA negative or ctDNA LFC ≥ 2 will continue to receive R-CHOP therapy for up to 6 courses. Potentially resistant patients with C1D14 ctDNA positive and LFC < 2 were stratified by DLBCL genotyping and treated with cycle 2-6 R-CHOP in combination with obutinib or decitabine or lenalidomide or Chidamide.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year progression-free survival (PFS) rate	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 years
2-year Overall survival (OS) rate	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.	2 years
The incidence and severity of adverse events were determined according to the NCI CTCAE v5.0 rating scale	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.	From enrollment to study completion, a maximum of 4 years

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): December 31, 2024
• Primary Completion (Estimated): December 13, 2026
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: December 12, 2024
• First Submitted That Met QC Criteria: December 22, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 22, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
• Other Study ID Numbers: 2023ZD0511200

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No