ctDNA-guided Therapy Optimization in Newly Diagnosed DLBCL

NCT06693830 | Recruiting DMC FDA Device

• 2 other identifiers: AAAU9823R03CA286676
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Diffuse Large B Cell Lymphoma; High-grade B-cell Lymphoma; Lymphoma; Lymphoma, B-Cell; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified

Keywords

circulating tumor DNA; measurable residual disease

Outcome Measures

Primary Outcomes (2)

• 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

  up to 5 months

• Complete Response Rate (CRR)

  Complete response rate as assessed by PET/CT scan in participants who receive de-escalated treatment

  up to 6 months

Secondary Outcomes (5)

• Rate of Minimal Residual Disease (MRD) Negativity

  Up to 4 months

• Time to ctDNA Result

  Up to 28 days

• Proportion of Participants Eligible for De-escalation

  Up to 5 months

• Progression Free Survival (PFS) Rate

  2 years

• Overall Survival (OS) Rate

  2 years

Study Arms (2)

Group 1

OTHER

All participants on this study will receive standard immunochemotherapy treatment for the first 4 cycles. Blood samples will be collected for real-time ctDNA sequencing with the PhasED-seq assay. Participants with undetectable ctDNA from the first day of cycle 4 and in a complete response (CR) on their PET/CT scan will get de-escalated treatment for cycle 5 and cycle 6 (rituximab alone without chemotherapy)

Device: Phased Variant Enrichment and Detection Sequencing (PhasED-seq); Other: De-escalated Treatment

Group 2

OTHER

All participants on this study will receive standard immunochemotherapy treatment for the first 4 cycles. Blood samples will be collected for real-time ctDNA sequencing with the PhasED-seq assay. Participants with detectable ctDNA, not in in a CR on PET/CT, and/or whose ctDNA sequencing was unsuccessful for any reason will continue standard of care for the remainder of treatment (cycle 5 and 6).

Device: Phased Variant Enrichment and Detection Sequencing (PhasED-seq); Other: Standard of Care Treatment

Interventions

Phased Variant Enrichment and Detection Sequencing (PhasED-seq) DEVICE

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.

Group 1; Group 2

Standard of Care Treatment OTHER

Standard of Care Treatment for cycles 1-6

Group 2

De-escalated Treatment OTHER

Standard of Care Treatment for cycles 1-4 and de-escalated treatment for cycles 5 and 6

Group 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age 18 years or older at time of screening
• Subject/legal representative willing and able to provide written informed consent
• Ability to comply with outpatient treatment, laboratory monitoring, and required clinic visits for duration of study participation
• Organ function as assessed by laboratory and cardiac function testing and Eastern Cooperative Oncology Group (ECOG) performance status in appropriate range for receipt of R-CHOP or R-pola-CHP at standard dose as per treating physician

You may not qualify if:

• Previous treatment for diffuse large B-cell lymphoma, except as outlined below:
• 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
• Radiation therapy for the treatment or prevention of spinal cord compression that has not started more than 28 days prior to enrollment
• Simultaneous participation in other treatment clinical protocol
• Planned anti-lymphoma therapies beyond R-CHOP or R-pola-CHP:
• Consolidative radiation to any baseline sites of disease
• Planned high-dose intravenous methotrexate for central nervous system (CNS) lymphoma prophylaxis (both mid-cycle and EOT excluded)
• Any number of doses of intrathecal chemotherapy for CNS lymphoma prophylaxis are allowed
• Transformed indolent lymphoma (including follicular lymphoma, marginal zone lymphoma, or lymphoplasmacytic lymphoma) or grade IIIB follicular lymphoma
• Known CNS involvement by lymphoma. R-CHOP and R-pola- CHP are insufficient to treat CNS disease.
• Any disease characteristics that would make R-CHOP or R-pola-CHP without radiation insufficient therapy at the discretion of the treating physician
• High-grade B-cell lymphoma with rearrangement of MYC and BCL2, primary mediastinal B-cell lymphoma, and HIV-associated lymphomas are excluded

Sponsors & Collaborators

• Foresight Diagnostics: collaborator
• Hua-Jay J Cherng, MD: lead
• Conquer Cancer Foundation: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Columbia University

New York, New York, 10032, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Neoplasm, Residual

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Hua-Jay J Cherng, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Research Nurse Navigator

CONTACT

212-342-5162; cancerclinicaltrials@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DEVICE FEASIBILITY
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: November 15, 2024
• First Posted: November 18, 2024
• Study Start: December 11, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2029
• Last Updated: January 23, 2026

Record last verified: 2026-01

Locations

US (1)