This clinical trial evaluates if real-time phased variant enrichment and detection sequencing (PhaseED-seq) circulating tumor deoxyribonucleic acid (ctDNA) assay can be used as a tool to guide therapy in newly diagnosed diffuse large B-cell lymphoma (DLBCL). DLBCL can be cured by the cyclophosphamide, doxorubicin, prednisone, rituximab and vincristine (R-CHOP) or cyclophosphamide, doxorubicin, prednisone, rituximab and polatuzumab vedotin (R-pola-CHP) treatment regimens. However, these treatments can cause side effects like nerve injury, fatigue, nausea and vomiting, pain, heart damage, infections, worse quality of life, and even second cancers. A blood test to measure tiny fragments of material released into the blood by lymphoma called ctDNA can be performed with blood draws. ctDNA is thought to be effective compared to standard imaging scans at detecting small amounts of residual disease that remain after treatment which can eventually cause the cancer to return. Standard treatment for newly diagnosed DLBCL is with 6 cycles of R-CHOP or R-pola-CHP without measurement of ctDNA or adjusting treatment based on mid-treatment response. Real-time measurement of ctDNA using the PhaseED-seq assay during standard R-CHOP or R-pola-CHP may reduce side effects, improve quality of life, and provide a faster return to baseline health for patients with undetectable ctDNA.
Additional locations may be listed on ClinicalTrials.gov for NCT06693830.
Locations matching your search criteria
United States
New York
New York
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer CenterStatus: Active
Contact: Hua-Jay Jeffery Cherng
Phone: 212-305-0591
PRIMARY OBJECTIVES:
I. Evaluate the feasibility of circulating tumor DNA (ctDNA) sequencing for real-time guidance of clinical decision making during frontline therapy for diffuse large B-cell lymphoma (DLBCL).
II. Determine outcomes of patients with newly diagnosed DLBCL who become undetectable for ctDNA and demonstrate a radiographic complete response during standard frontline therapy and discontinue chemotherapy early.
SECONDARY OBJECTIVES:
I. Estimate the rate of interim ctDNA negativity during standard frontline therapy for DLBCL.
II. Assess the proportion of patients eligible for chemotherapy de-escalation during standard frontline therapy for DLBCL.
III. Assess the adverse events associated with a de-escalated course of frontline therapy for DLBCL or standard treatment.
IV. Evaluate the concordance between positron emission tomography (PET) response assessment with ctDNA detection status during frontline therapy for DLBCL.
EXPLORATORY OBJECTIVES:
I. Assess the risk of molecular relapse after therapy de-escalation.
II. Evaluate the concordance between novel PET quantitative and radiomics features with ctDNA status during frontline therapy for DLBCL.
III. Evaluate patient reported outcomes and patient reported adverse events associated with a de-escalated course of frontline therapy for DLBCL or standard treatment.
IV. Evaluate markers of cardiac injury associated with a de-escalated course of frontline therapy for DLBCL or standard treatment.
OUTLINE: Patients are assigned to 1 of 2 arms.
ARM I: Patients receive standard of care rituximab, cyclophosphamide, doxorubicin, and vincristine intravenously (IV) on day 1, as well as prednisone orally (PO) days 1-5 of each cycle (R-CHOP) or rituximab, polatuzumab vedotin, cyclophosphamide, and doxorubicin IV on day 1, as well as prednisone orally (PO) days 1-5 of each cycle (R-pola-CHP). Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ctDNA blood sample collection on cycle (C) 4 day (D) 1. Patients with successful ctDNA sequencing, who are minimal residual disease (MRD) negative (undetectable ctDNA) on C4D1, and in a complete response (CR) de-escalate treatment to rituximab IV alone on day 1 of each cycle for cycles 5-6 in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography (ECHO) during screening, as well as blood sample collection and positron emission tomography (PET)/computed tomography (CT) or CT throughout the study.
ARM II: Patients receive standard of care rituximab, cyclophosphamide, doxorubicin, and vincristine IV on day 1, as well as prednisone PO days 1-5 of each cycle (R-CHOP) or rituximab, polatuzumab vedotin, cyclophosphamide, and doxorubicin IV on day 1, as well as prednisone PO days 1-5 of each cycle (R-pola-CHP). Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ctDNA blood sample collection on C4D1. Patients with failure of ctDNA sequencing, are MRD positive (detectable ctDNA) on C4D1, and/or are not in a CR continue standard therapy, which may include continuing R-CHOP/R-pola-CHP for cycles 5-6 in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening, as well as blood sample collection and PET/CT or CT throughout the study.
After completion of study intervention, patients are followed up at 3-4 and 12-14 weeks post cycle 6 day 1, and at 6, 12, and 24 months.
Trial PhaseNo phase specified
Trial Typesupportive care
Lead OrganizationNYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
Principal InvestigatorHua-Jay Jeffery Cherng
