Dynamic CtDNA-guided Targeted Therapy in DLBCL

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.

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Key information

Conditions

Diffuse Large B Cell Lymphoma (DLBCL) Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

R-CHOP + X

Drug

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.

Primary outcomes

Complete response (CR) rate

Time frame: 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 outcomes

2-year progression-free survival (PFS) rate

Time frame: 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

Time frame: 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

Time frame: 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Weili Zhao, MD, PhD

CONTACT

[email protected]

+862164370045 ext. 610707

Sponsors and collaborators

Lead sponsor

Ruijin Hospital

Other

Registry information

Official study title

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

Important dates

Study start: 2024
Primary completion: 2026
Study completion: 2028
First posted: Dec 27, 2024
Registry last updated: Dec 27, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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