LymphomaNCT06693830
ctDNA-guided Therapy Optimization in Newly Diagnosed DLBCL
A study testing Phased Variant Enrichment and Detection Sequencing (PhasED-seq) and De-escalated Treatment in people with Lymphoma and Lymphoma, B-Cell, run by Hua-Jay J Cherng, MD at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, Lymphoma, B-Cell, Diffuse Large B Cell Lymphoma
- What is being tested?
- Phased Variant Enrichment and Detection Sequencing (PhasED-seq) and De-escalated Treatment
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Dec 2024to Dec 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Columbia University
New York, New York, 10032
Research Nurse Navigator, 212-305-0591, cancerclinicaltrials@cumc.columbia.edu
Hua-Jay J Cherng, MD
About this study
Official title: Sequencing-guided cHemotherapy Optimization Using Real-Time Evaluation in Newly Diagnosed DLBCL With Circulating Tumor DNA: SHORTEN-ctDNA
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).
Read the detailed 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 study an anticipated 40 patients with newly diagnosed DLBCL will be screened for a target enrollment goal of 32 participants. These 32 patients will receive standard treatment with 4 cycles of R-CHOP or R-pola-CHP immunochemotherapy. These patients will have blood samples collected after 3 cycles to test for the presence of ctDNA in real-time. Patients who have successful real-time sequencing and have undetected ctDNA as well as a complete remission on interim re-staging scans will de-escalate treatment and omit chemotherapy for their final 2 cycles of treatment. These patients will receive rituximab alone for their final 2 cycles. All others will continue standard treatment.
26 participants are expected to have successful real-time sequencing, of which 13 patients are expected to meet criteria for treatment de-escalation and omit chemotherapy for their final 2 cycles of treatment.
- Conditions
- Lymphoma, Lymphoma, B-Cell, Diffuse Large B Cell Lymphoma, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, High-grade B-cell Lymphoma
- Being tested
- Phased Variant Enrichment and Detection Sequencing (PhasED-seq), Standard of Care Treatment, De-escalated Treatment
- Keywords
- circulating tumor DNA, measurable residual disease
- Medical subject headings
- Lymphoma, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Neoplasm, Residual
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
Standard of Care TreatmentOther
Standard of Care Treatment for cycles 1-6
De-escalated TreatmentOther
Standard of Care Treatment for cycles 1-4 and de-escalated treatment for cycles 5 and 6
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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). Receives: Device: Phased Variant Enrichment and Detection Sequencing (PhasED-seq); Other: Standard of Care Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: up to 5 months
Complete Response Rate (CRR)
Complete response rate as assessed by PET/CT scan in participants who receive de-escalated treatment
Measured: up to 6 months
Secondary outcomes (5)
Rate of Minimal Residual Disease (MRD) Negativity
MRD negativity defined as ctDNA negativity as determined by blood sample analysis
Measured: Up to 4 months
Time to ctDNA Result
Time from sample collection to ctDNA result
Measured: Up to 28 days
Proportion of Participants Eligible for De-escalation
The proportion of participants eligible for de-escalation
Measured: Up to 5 months
Progression Free Survival (PFS) Rate
PFS defined as the time between C1D1 of therapy and progression of DLBCL.
Measured: 2 years
Overall Survival (OS) Rate
OS defined as the time between C1D1 of therapy and death from any cause.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2024
- Study start11 Dec 2024
- Primary completionDec 2027 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Device feasibility
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hua-Jay J Cherng, MD
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Conquer Cancer Foundation, Foresight Diagnostics
- Responsible party
- Sponsor-investigator, Hua-Jay J Cherng, MD, Columbia University
- Investigators
- Hua-Jay J Cherng, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06693830
- Sponsor's protocol ID
- AAAU9823
- Other IDs
- R03CA286676
- Status last verified
- Jan 2026
- First submitted
- 15 Nov 2024
- Last updated
- 23 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sequencing-guided cHemotherapy Optimization Using Real-Time Evaluation in Newly Diagnosed DLBCL With Circulating Tumor DNA: SHORTEN-ctDNA
- ClinicalTrials.gov ID
- NCT06693830
- Acronym / sponsor ID
- AAAU9823
- Conditions
- Lymphoma, Lymphoma, B-Cell, Diffuse Large B Cell Lymphoma, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, High-grade B-cell Lymphoma
- Keywords
- circulating tumor DNA, measurable residual disease
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Hua-Jay J Cherng, MDUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Conquer Cancer Foundation, Foresight Diagnostics
- Study start
- 11 Dec 2024 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 18 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed 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 study an anticipated 40 patients with newly diagnosed DLBCL will be screened for a target enrollment goal of 32 participants. These 32 patients will receive standard treatment with 4 cycles of R-CHOP or R-pola-CHP immunochemotherapy. These patients will have blood samples collected after 3 cycles to test for the presence of ctDNA in real-time. Patients who have successful real-time sequencing and have undetected ctDNA as well as a complete remission on interim re-staging scans will de-escalate treatment and omit chemotherapy for their final 2 cycles of treatment. These patients will receive rituximab alone for their final 2 cycles. All others will continue standard treatment.
26 participants are expected to have successful real-time sequencing, of which 13 patients are expected to meet criteria for treatment de-escalation and omit chemotherapy for their final 2 cycles of treatment.
Study design
- Primary purpose
- Device feasibility
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Other | Device: Phased Variant Enrichment and Detection Sequencing (PhasED-seq), Other: De-escalated TreatmentAll 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) |
| Group 2 | Other | Device: Phased Variant Enrichment and Detection Sequencing (PhasED-seq), Other: Standard of Care TreatmentAll 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients with newly diagnosed, histologically confirmed CD20+ DLBCL
- 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
Key exclusion criteria (27 listed)
- Previous treatment for diffuse large B-cell lymphoma, except as outlined below:
- Simultaneous participation in other treatment clinical protocol
- Planned anti-lymphoma therapies beyond R-CHOP or R-pola-CHP:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Device | Group 1, Group 2 |
| Standard of Care TreatmentStandard of Care Treatment for cycles 1-6 | Other | Group 2 |
| De-escalated TreatmentStandard of Care Treatment for cycles 1-4 and de-escalated treatment for cycles 5 and 6 | Other | Group 1 |
Primary outcome
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
5 secondary outcomes
Rate of Minimal Residual Disease (MRD) Negativity
Time frame: Up to 4 months
Time to ctDNA Result
Time frame: Up to 28 days
Proportion of Participants Eligible for De-escalation
Time frame: Up to 5 months
Progression Free Survival (PFS) Rate
Time frame: 2 years
Overall Survival (OS) Rate
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Hua-Jay J Cherng, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Phased Variant Enrichment and Detection Sequencing (PhasED-seq) and De-escalated Treatment in people with Lymphoma and Lymphoma, B-Cell, run by Hua-Jay J Cherng, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Research Nurse Navigator (212-342-5162, cancerclinicaltrials@cumc.columbia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Success Rate of Real-Time Circulating Tumor DNA (ctDNA) Sequencing (time frame: up to 5 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2026.