Trials / Recruiting

RecruitingNCT06693830

ctDNA-guided Therapy Optimization in Newly Diagnosed DLBCL

Sequencing-guided cHemotherapy Optimization Using Real-Time Evaluation in Newly Diagnosed DLBCL With Circulating Tumor DNA: SHORTEN-ctDNA

Status: Recruiting
Phase: N/A
Study type: Interventional
Enrollment: 40 (estimated)

Sponsor: Hua-Jay J Cherng, MD · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

The purpose of this study is to 1) determine whether it is feasible to measure circulating tumor DNA (ctDNA) in real-time during standard treatment for newly diagnosed diffuse large B-cell lymphoma (DLBCL), and 2) evaluate the outcomes of participants with undetectable ctDNA in the middle of treatment who receive a shortened course of chemotherapy. There are no investigational drug agents to be administered in this study. The investigational assay, phased variant enrichment and detection sequencing (PhasED-seq) will be used to guide de-escalation of standard-of-care therapy for newly diagnosed DLBCL. The PhasED-seq assay has not yet been approved by the Food and Drug Administration (FDA).

Detailed description

The feasibility of real-time ctDNA sequencing with PhasED-seq during DLBCL therapy has yet to be established. There are logistical challenges to developing a consistent and efficient workflow for obtaining, processing, and sequencing patient samples during frontline immunochemotherapy. ctDNA sequencing must be reliable with a low failure rate before it can be adopted as an integral biomarker for treatment decision making in the clinic. Furthermore, the outcomes of patients who have undetectable ctDNA with PhasED-seq during treatment who de-escalate their chemotherapy must be assessed. In this study an anticipated 40 patients with newly diagnosed DLBCL will be screened for a target enrollment goal of 32 participants. These 32 patients will receive standard treatment with 4 cycles of R-CHOP or R-pola-CHP immunochemotherapy. These patients will have blood samples collected after 3 cycles to test for the presence of ctDNA in real-time. Patients who have successful real-time sequencing and have undetected ctDNA as well as a complete remission on interim re-staging scans will de-escalate treatment and omit chemotherapy for their final 2 cycles of treatment. These patients will receive rituximab alone for their final 2 cycles. All others will continue standard treatment. 26 participants are expected to have successful real-time sequencing, of which 13 patients are expected to meet criteria for treatment de-escalation and omit chemotherapy for their final 2 cycles of treatment.

Conditions

Interventions

Type	Name	Description
DEVICE	Phased Variant Enrichment and Detection Sequencing (PhasED-seq)	PhasED-seq designed to detect minimal residual disease (MRD) as indicated by the presence of circulating tumor DNA (ctDNA) evidenced by an aggregate signal of phased variants (PVs) in the plasma of patients diagnosed with large B-cell lymphoma (LBCL) following first-line therapy.
OTHER	Standard of Care Treatment	Standard of Care Treatment for cycles 1-6
OTHER	De-escalated Treatment	Standard of Care Treatment for cycles 1-4 and de-escalated treatment for cycles 5 and 6

Timeline

Start date: 2024-12-11
Primary completion: 2027-12-01
Completion: 2029-12-01
First posted: 2024-11-18
Last updated: 2026-01-23

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated device study

Source: ClinicalTrials.gov record NCT06693830. Inclusion in this directory is not an endorsement.