Study on Predicting Response to Standard First-Line Treatment in Diffuse Large B-Cell Lymphoma (DLBCL) Patients Using ctDNA Combined With PET

Official title

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

Overview

This is a prospective, multicenter, multi-cohort study of ctDNA combined with PET for predicting the efficacy of standard first-line therapy for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).

Detailed description

This multicenter, prospective, multi-cohort clinical study was designed to evaluate the relevance of combined test results for PET / CT and ctDNA and patient survival outcomes in patients with naive DLBCL after 2 cycles of treatment with the standard first-line therapy. The study plans to enroll 80 patients with newly diagnosed, CD20-positive DLBCL who have not received prior systemic therapy. Participants will be stratified into two cohorts based on baseline International Prognostic Index (IPI) scores, receiving either the NMPA-approved R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or the NMPA-approved Pola-R-CHP regimen (polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, prednisone) for 6 cycles. PET/CT imaging will be performed at baseline, Cycle 2 Day 20 (C2D20), and 6 weeks after Cycle 6 Day 21 (C6D21), while whole-blood samples for circulating tumor DNA (ctDNA) analysis will be collected at baseline, Cycle 3 Day 1 (C3D1), and C6D21.The primary endpoint of this study is the association of PET / CT and ctDNA test results with progression-free survival (PFS) after 2 cycles of RCHOP or Pola-R-CHP regimen in treatment-naive patients with diffuse large B cell lymphoma (DLBCL). Secondary endpoints are the correlation between the combination of PET / CT and ctDNA with tumor remission after 2 cycles of RCHOP or Pola-R-CHP in DLBCL patients, association of PET / CT and ctDNA with RCHOP or Pola-R-CHP and assessment of the CR rate, ORR, EFS and safety of real-world RCHOP or Pola-R-CHP regimen in treatment-naive DLBCL patients.

Interventions

• Drug POLA-R-CHP
  Pola-R-CHP treatment for 6 cycles (IPI score 2-5)

Primary outcome measures

• Correlation between combined PET/CT and ctDNA assessments after 2 cycles of R-CHOP or Pola-R-CHP therapy and progression-free survival (PFS) [Time frame: Baseline, Day 20 of Cycle 2, and 6 weeks after Cycle 6 completion（each cycle is 21 days）]

Secondary outcome measures (1)

• Correlation between combined PET/CT and ctDNA assessments after 2 cycles of R-CHOP or Pola-R-CHP therapy and tumor response and overall survival (OS) in treatment-naive DLBCL patients [Time frame: Through study completion, an average of 2 year"]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 1 center

• Fudan University Shanghai Cancer Center — Shanghai

Identifiers

NCT: NCT07070648 · SHCA-HEMA-03

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗