Predicting response to first-line DLBCL treatment using ctDNA and PET/CT

Study on Predicting Response to Standard First-Line Treatment in Diffuse Large B-Cell Lymphoma (DLBCL) Patients Using ctDNA Combined With PET: A Prospective, Multicenter, Multicohort Investigation

This project will test whether combining a blood ctDNA test with PET/CT scans after two treatment cycles can predict treatment response in people newly diagnosed with DLBCL who are starting standard first-line therapy.

Quick facts

• Study type: Observational
• Enrollment: 300 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: chemotherapy, rituximab, polatuzumab, cyclophosphamide, doxorubicin, prednisone
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07070648 on ClinicalTrials.gov

What this trial studies

This is a prospective, multicenter, multi-cohort study enrolling about 80 adults with newly diagnosed, CD20‑positive DLBCL who have not received prior systemic therapy. Participants are stratified by baseline International Prognostic Index (IPI) and receive six cycles of either R‑CHOP or Pola‑R‑CHP, with PET/CT at baseline, Cycle 2 Day 20, and six weeks after Cycle 6 Day 21. Whole-blood samples for circulating tumor DNA (ctDNA) are collected at baseline, Cycle 3 Day 1, and six weeks after Cycle 6 Day 21 to compare molecular response with imaging. The primary aim is to see if PET and ctDNA results after two cycles are associated with progression-free survival, with secondary endpoints including remission rates and correlation of combined testing with treatment outcomes.

Who should consider this trial

Good fit: Adults (≥18) with newly diagnosed, CD20‑positive DLBCL, ECOG performance status 0–2, measurable disease, and no prior systemic therapy who can attend the study center are the intended participants.

Not a fit: Patients who have already received systemic therapy, lack measurable PET‑avid disease or detectable ctDNA, or cannot travel to the Shanghai study center are unlikely to gain benefit from participation.

Why it matters

Potential benefit: If successful, combining ctDNA and PET/CT could identify non-responders earlier so therapy can be changed sooner, potentially improving outcomes and avoiding ineffective treatment.

How similar studies have performed: Previous studies have shown interim PET and ctDNA individually have prognostic value in DLBCL, and early data suggest combining them may improve prediction, but large prospective validation remains limited.

Eligibility criteria

Inclusion Criteria:

* Age ≥ 18 years old.
* Previously untreated CD20-positive DLBCL patients, including the following types according to the 2016 WHO classification of lymphoid neoplasms: DLBCL, not otherwise specified (NOS) including germinal center B-cell type and activated B-cell type; T-cell/histiocyte-rich large B-cell lymphoma; Epstein - Barr virus-positive DLBCL, NOS; ALK-positive large B-cell lymphoma; HHV8-positive DLBCL, NOS; high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double-hit or triple-hit lymphoma); high-grade B-cell lymphoma, NOS.
* Signed informed consent form (ICF).
* Eastern Cooperative Oncology Group (ECOG) performance status score 0 - 2, with an expected survival greater than 12 months.
* Have at least one measurable two-dimensional lesion determined by clinical examination, CT scan, or MRI: ① lymph nodes \> 1.5 cm; ② other non-lymph node lesions ≥ 1.0 cm.
* Good function of major organs: Hematological function: absolute neutrophil count ≥ 1,000/mm³, platelet count ≥ 75,000/mm³; Liver function: ALT/AST \< 3 times the upper limit of normal (ULN) and total bilirubin ≤ 1.5× ULN (for patients with Gilbert syndrome, hilar compressive adenopathy-induced cholestasis, liver involvement or lymphoma-induced biliary obstruction \< 5 times ULN); Renal function: creatinine clearance \> 30 mL/min, creatinine ≤ 1.5× ULN; Pulmonary function: indoor oxygen saturation ≥ 95%; Cardiac function: no obvious cardiac insufficiency or cardiovascular disease.
* Fertile patients must be willing to take highly effective contraceptive measures during the study and within 120 days after the last administration of treatment.

Exclusion Criteria:

* Patients planned to receive short-cycle chemotherapy and radiotherapy.
* Subjects judged by the investigator to have any factors affecting compliance with the protocol, including uncontrollable medical, psychological, family, sociological or geographical conditions; or unwilling or unable to comply with the procedures required in the study protocol.
* Known human immunodeficiency virus (HIV) infection or positive immunassay.
* Viral infections that cannot be controlled by antiviral drugs, such as herpesvirus active infection, acute or chronic active hepatitis B, acute or chronic active hepatitis C, etc. (Note: Chronic HBV carriers or inactive HBsAg-positive subjects with HBV-DNA below the detection limit can be enrolled, requiring clinical evaluation, and if appropriate, preventive antiviral treatment is required; HCV antibody-negative subjects can be enrolled, and HCV antibody-positive patients need to be tested for HCV-RNA, and if negative, they can be enrolled).
* Patients with uncontrolled lymphoma central nervous system infiltration (central nervous system diseases diagnosed at the initial diagnosis are allowed, provided that complete remission of central nervous system diseases is achieved and maintained and there is no central nervous system disease at recurrence).
* Pregnant or lactating patients.
* Other concurrent serious diseases or medical conditions that would interfere with participation in the study.

Where this trial is running

Shanghai, Shanghai Municipality

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Rong Tao, M.D

Conditions Diffuse Large B-Cell Lymphoma; DLBCL; ctDNA; PET-CT