A phase II efficacy and safety study of cell-free circulating tumor DNA-guided commencement of second-line treatment in patients with DLBCL/HGBCL relapse

Trial details

Who runs it

Instytut Hematologii I Transfuzjologii

Trial code

EU 2024-518275-64-00

Record updated

2026. augusztus 28.

Original description

The primary objective of the proposed phase 2 study is to evaluate the efficacy and safety of an intervention involving early implementation of second-line treatment in DLBCL/HGBCL patients, initiated based on eligibility including assessment of circulating tumor-derived DNA.Read full original descriptionShow less

The primary objective of the proposed phase 2 study is to evaluate the efficacy and safety of an intervention involving early implementation of second-line treatment in DLBCL/HGBCL patients, initiated based on eligibility including assessment of circulating tumor-derived DNA.

Inclusion: Stage I - prescreening 1. patients with a diagnosis of DLBCL or HGBCL, eligible for chemotherapy according to the R-CHOP or R-CHOP-like regimen (DLBCL) or Pola-R-CHP (DLBCL) or DA-EPOCH-R (HGBCL); Available results of the following tests: - quantitative and qualitative analysis of mutation assessment in peripheral blood by CAPP-Seq and ddPCR prior to the start of first-line treatment, or a secured blood sample allowing such analysis; - Quantitative assessment of circulating free DNA (cfDNA) of tumor origin during treatment (after the 2nd cycle of R-CHOP or R-CHOP-like in DLBCL patients, after the 2nd cycle of DA-EPOCH-R in HGBCL patients) and after completion of 1st line treatment or secured blood samples enabling such analysis; - PET-CT before inclusion of first-line treatment and after completion of first-line treatment - PET-CT or CT during 1st line treatment (after 2nd or 3rd cycle of R-CHOP or R-CHOP-like or Pola-R-CHP in DLBCL, after 2nd or 3rd cycle of DA-EPOCH-R for HGBCL); Signing informed consent to participate in Phase II clinical trial.); Age ≥18 years; Perform a PET/CT scan to assess disease progression before starting treatment (a description of the result does not have to be available on the day the patient is included in the study); Age ≥18 years; ECOG 0-2 or ECOG 3, if the general condition is due to disease progression; Consent to effective contraception during the trial with contraception for 14 months for women and 11 months for men after the last dose of immunochemotherapy 6. In women of childbearing age, a negative serum pregnancy test at screening and agreement to use highly effective contraception during the trial and for 14 months after the last dose of chemotherapy (except for patients over 50 years of age with natural amenorrhea for at least 12 months or after a bilateral salpingo-oophorectomy or hysterectomy); Signing consent to participate in Phase I clinical trial; Provide access to histopathological material from the disease diagnosis in case of technical difficulties in obtaining sufficient genetic material from cfDNA; In the case of planned treatment with Pola-R-CHP, meeting the general and specific eligibility criteria for first-line therapy according to drug program B.12; Stage II Patients diagnosed with DLBCL or HGBCL, in complete remission (CR) confirmed by PET-CT after completion of first-line treatment (R-CHOP or R-CHOP-like or Pola-R-CHP in DLBCL patients, DA-EPOCH-R in HGBCL patients). Modifications of standard R-CHOP immunochemotherapy to, for example, R-CHOP-14, addition of etoposide (R-CHOEP), dose changes due to comorbidities or side effects are allowed.

Exclusion: Treatment for malignant neoplasm other than basal cell carcinoma of the skin less than 5 years prior to study inclusion; The following test results are not available: - quantitative and qualitative analysis of peripheral blood mutation assessment by CAPP-Seq and ddPCR prior to initiation of first-line treatment, or a secured blood sample allowing such analysis; - quantitative assessment of circulating tumor-derived free DNA (cfDNA) during treatment (after the 2nd cycle of R-CHOP or R-CHOP-like or Pola-R-CHP in DLBCL patients, after the 2nd cycle of DA-EPOCH-R in HGBCL patients) and after completion of first-line treatment, or secured blood samples enabling such analysis; Treatmentdue due to malignant neoplasm other than basal cell carcinoma of the skin less than 5 years prior to study inclusion; Stage I - prescreening Richter syndrome, transformation to DLBCL of indolent lymphomas, G3B follicular lymphoma, lymphomas with intermediate features between DLBCL and Hodgkin's lymphoma; Active second primary malignancy other than basal cell carcinoma of the skin; n addition, for treatment under drug program B.12: (a) disease progression during treatment; (b) occurrence of symptoms of hypersensitivity to any of the drugs used or to mouse proteins or any of the excipients of the formulations; (c) occurrence of intolerable or life-threatening toxicity despite adequate management; (d) diagnosis of progressive multifocal leukoencephalopathy (PML); (e) the occurrence of diseases or conditions that, in the judgment of the treating physician attending physician makes it impossible to continue treatment; Active second primary malignancy other than basal cell carcinoma of the skin; For planned treatment with vedotin polatuzumab under drug program B.12: (a) active, severe infection; (b) bilirubin levels exceeding 1.5 times the upper limit of normal for the laboratory; (c) peripheral neuropathy ≥ grade 2; (d) presence of contraindications to the use of vedotin polatuzumab, bendamustine and rituximab, which are derived from the Summary Product Chracteristcs; creatinine clearance <30 ml/min; Creatinine clearance <30 ml/min; Pregnancy and breastfeeding; Any other significant abnormality that, in the opinion of the Investigator, excludes the patient from participation in the study or prevents the application of the planned treatment regimens; inability of the patient to sign the informed consent form; Stage II Lack of CR after completion of first-line treatment; Pregnancy and breastfeeding; Any other significant abnormality that, in the opinion of the Investigator, excludes the patient from participation in the study or prevents the application of the planned treatment regimens; inability of the patient to sign the informed consent form; inability of the patient to sign the informed consent form; Stage III DLBCL/HGBCL lymphoma with secondary central nervous system involvement; DLBCL lymphoma with primary central nervous system involvement.

EU CTIS 2024-518275-64-00