NCT06693830 · Hua-Jay J Cherng, MD
ctDNA-guided Therapy Optimization in Newly Diagnosed DLBCL
What this study is about
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.
View original scientific description
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).
Interventions
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
Primary outcome measures
Success Rate of Real-Time Circulating Tumor DNA (ctDNA) Sequencing
Time frame: up to 5 months
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)
Time frame: up to 6 months
Complete response rate as assessed by PET/CT scan in participants who receive de-escalated treatment
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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
Exclusion criteria
- 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
- Richter transformation of chronic lymphocytic leukemia
- Pregnancy and/or nursing period. R-CHOP and R-pola-CHP may cause fetal harm or birth defects, and effects of exposure in the breastfed infant are unknown.
- A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "childbearing potential"
- Women of childbearing potential are eligible if a negative serum or urine beta human chorionic gonadotropin pregnancy test is documented within 28 days of screening, and they must agree to us an effective contraception method during systemic treatment
- Men who have partners of childbearing potential must agree to use an effective contraceptive method during systemic treatment
- In addition to routine contraceptive methods, "acceptable contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen.
- Uncontrolled active systemic infection
- Patients with a positive hepatitis B virus (HBV) core antibody and negative HBV surface antigen consistent with prior HBV exposure must be willing to take appropriate anti-viral prophylaxis.
- Patients with evidence of chronic HBV infection must have undetectable HBV viral load on the most recent test results obtained within the last year and received suppressive therapy.
- Participants with a history of hepatitis C virus (HCV) infection must have an undetectable viral load. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 28 days prior to consent.
- Active second malignancy unless in remission and with life expectancy \> 2 years with exception of patients diagnosed with basal cell or squamous cell carcinoma of the skin or carcinoma "in situ" of the cervix or breast who are eligible even if diagnosed within 2 years. If patients have another malignancy that was treated within the last 2 years, such patients may be enrolled, if the likelihood of requiring systemic therapy for this other malignancy within 2 years is less than 10%, as determined by an expert in that particular malignancy at CUIMC, and after consultation with the Principal Investigator. Hormone therapy for treated prostate and breast cancer is allowed.
- Known hypersensitivity to any component of R-CHOP or R-pola-CHP
Where
- New York, New York
Collaborators
National Cancer Institute (NCI), Conquer Cancer Foundation, Foresight Diagnostics
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jan 23, 2026 · Source of record for eligibility and locations