2024-518275-64-00招募中2 期
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
Instytut Hematologii I Transfuzjologii9 个研究点 分布在 1 个国家目标入组 340 人开始时间: 2024年12月2日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 340
- 试验地点
- 9
- 主要终点
- ORR for second-line treatment initiated based on a diagnostic algorithm that takes into account cfDNA levels.
研究概览
简要总结
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.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Stage I - prescreening
- •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).
- •Signed consent to participate in the Phase I clinical trial.
- •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.
- •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.
排除标准
- •Stage I - prescreening Richter syndrome, transformation to DLBCL of indolent lymphomas, G3B follicular lymphoma, lymphomas with intermediate features between DLBCL and Hodgkin's lymphoma.
- •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.
- •Active second primary malignancy other than basal cell carcinoma of the skin.
- •Treatment for malignant neoplasm other than basal cell carcinoma of the skin less than 5 years prior to study inclusion.
- •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.
- •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.
- •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;
- •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
- •inability of the patient to sign the informed consent form.
- •Stage III DLBCL/HGBCL lymphoma with secondary central nervous system involvement.
- •creatinine clearance <30 ml/min.
- •DLBCL lymphoma with primary central nervous system involvement.
- •Creatinine clearance <30 ml/min.
- •Active second primary malignancy other than basal cell carcinoma of the skin
- •Treatmentdue due to malignant neoplasm other than basal cell carcinoma of the skin less than 5 years prior to study inclusion.
结局指标
主要结局
ORR for second-line treatment initiated based on a diagnostic algorithm that takes into account cfDNA levels.
ORR for second-line treatment initiated based on a diagnostic algorithm that takes into account cfDNA levels.
The incidence of grade 3 and 4 adverse reactions assessed according to CTCAE v. 5.
The incidence of grade 3 and 4 adverse reactions assessed according to CTCAE v. 5.
次要结局
- Assessment of health-related quality of life using the EORTC QLQ-C30 generic questionnaire.
- Sensitivity, specificity, PPV, NPV of circulating DNA assay measured by NGS and/or ddPCR (individually selected markers) after first-line treatment in relation to the likelihood of maintaining CR status at 36 months of follow-up
- TTNT since the end of first-line treatment, which will be referenced to archival/historical groups of patients treated at hematology centers collaborating in the PLRG
研究者
Instytut Hematologii I Transfuzjologii
Scientific
Instytut Hematologii I Transfuzjologii
研究点 (9)
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