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).
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.
Up to 14 days of corticosteroids for the relief of lymphoma-related symptoms
A dose of pre-phase vincristine or rituximab
One cycle of R-chemotherapy (including but not limited to R-CHOP, R-pola-CHP, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab [DA-EPOCH-R) that has not started more than 28 days prior to consent
Intrathecal chemotherapy for central nervous system (CNS) prophylaxis
Sequential
Phased Variant Enrichment and Detection Sequencing (PhasED-seq)
DevicePhasED-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.
Standard of Care Treatment
Other interventionStandard of Care Treatment for cycles 1-6
De-escalated Treatment
Other interventionStandard of Care Treatment for cycles 1-4 and de-escalated treatment for cycles 5 and 6
Success Rate of Real-Time Circulating Tumor DNA (ctDNA) Sequencing
Success defined as: C4D1 sample collected, DNA successfully sequenced from the diagnostic tissue sample, C4D1 timepoint result must be available within 28 days of C4D1
Complete Response Rate (CRR)
Complete response rate as assessed by PET/CT scan in participants who receive de-escalated treatment
Rate of Minimal Residual Disease (MRD) Negativity
MRD negativity defined as ctDNA negativity as determined by blood sample analysis
Time to ctDNA Result
Time from sample collection to ctDNA result
Proportion of Participants Eligible for De-escalation
The proportion of participants eligible for de-escalation
Progression Free Survival (PFS) Rate
PFS defined as the time between C1D1 of therapy and progression of DLBCL.
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Hua-Jay J Cherng, MD
Lead sponsor
Columbia University
Sponsor institution
National Cancer Institute (NCI)
Collaborator
Conquer Cancer Foundation
Collaborator
Foresight Diagnostics
Collaborator
