Sequencing-guided cHemotherapy Optimization Using Real-Time Evaluation in Newly Diagnosed DLBCL With Circulating Tumor DNA: SHORTEN-ctDNA
Hua-Jay J Cherng, MD
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).
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…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Patients with newly diagnosed, histologically confirmed CD20+ DLBCL * Stage II-IV disease * Planned for anthracycline-based therapy with standard dosed R-CHOP or R-pola- CHP without consolidative radiation * Measurable disease on cross sectional imaging ≥ 1.5 cm in longest diameter and measurable in two perpendicular dimensions, with at least one corresponding hypermetabolic lesion by Lugano classification on baseline FDG PET/CT or CT with intravenous contrast of the chest, abdomen, and pelvis if FDG PET/CT not available. 2. Age 18 years or older at time of sc…
Interventions
- DevicePhased 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.
- OtherStandard of Care Treatment
Standard of Care Treatment for cycles 1-6
- OtherDe-escalated Treatment
Standard of Care Treatment for cycles 1-4 and de-escalated treatment for cycles 5 and 6
Location
- Columbia UniversityNew York, New York