Brentuximab vedotin for Peripheral T-cell lymphoma (PTCL) | Anaplastic large cell lymphoma (ALCL) | Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) | Angioimmunoblastic T-cell lymphoma (AITL) | Adult T-cell leukaemia/lymphoma (ATLL) | Enteropathy-associated T-cell lymphoma (EATL) | Hepatosplenic T-cell lymphoma | Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) | Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract | Follicular T-cell lymphoma | Nodal peripheral T-cell lymphoma with T-follicular helper phenotype

Inclusion criteria

• {"criterion_text":"- 1.\tAge >18 years"}
• {"criterion_text":"- 2.\tWritten informed consent"}
• {"criterion_text":"- 3.\tHistologically confirmed diagnosis of CD30-expressing PTCL. The following histological subtypes according to the Revised European-American Lymphoma World Health Organization (WHO) 2016 classification are eligible: a.\tSystemic anaplastic large cell lymphoma (ALCL) ALK+ with age-adjusted international prognostic index (aaIPI) ≥1 b.\tSystemic anaplastic large cell lymphoma (ALCL) ALK- c.\tPeripheral T-cell lymphoma not otherwise specified (PTCL-NOS) d.\tAngioimmunoblastic T-cell lymphoma (AITL) e.\tAdult T-cell leukaemia/lymphoma (ATLL; acute and lymphoma types only, must be positive for human T cell leukaemia virus 1) f.\tEnteropathy-associated T-cell lymphoma (EATL) g.\tHepatosplenic T-cell lymphoma h.\tMonomorphic epitheliotropic intestinal T-cell lymphoma (MEITCL) i.\tIndolent T-cell lymphoproliferative disorder (T-LPD) of the gastrointestinal (GI) tract j.\tFollicular T-cell lymphoma k.\tNodal peripheral T-cell lymphoma with T-follicular helper (TFH) phenotype"}
• {"criterion_text":"- 4.\tPositive CD30 expression by local pathology assessment."}
• {"criterion_text":"- 5.\tPatients must have at least one measurable disease site. The lesion must be fluorodeoxyglucose (FDG)-avid by PET and must have a greatest transverse diameter of ≥1.5 cm and greatest perpendicular diameter of ≥1.0 cm by CT, as assessed by the site radiologist."}
• {"criterion_text":"- 6.\tEastern Cooperative Oncology Group (ECOG, Appendix B) performance status of 0 to 1"}
• {"criterion_text":"- 7.\t Patient must be autologous stem cell transplant (ASCT)-eligible"}
• {"criterion_text":"- 8.\t Patient must be appropriate candidate for treatment with anthracyclines"}
• {"criterion_text":"- 9.\tPatient must have the following laboratory criteria at screening: a.\tAbsolute neutrophil count (ANC) ≥ 1.0 x 109/L (unless secondary to bone marrow involvement by PTCL) b.\tPlatelet count ≥ 50 x 109/L (unless secondary to bone marrow involvement by PTCL) c.\tTotal serum bilirubin < 1.5 × upper limit of normal (ULN) unless secondary to Gilbert’s syndrome or documented liver involvement by lymphoma. Patients with Gilbert’s syndrome or documented liver involvement by lymphoma may be included if their total bilirubin is ≤3 × ULN d.\tAlanine transaminase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) ≤3 × ULN, or <5 × ULN in cases of documented liver involvement by lymphoma e.\tSerum creatinine clearance must be >50 mL/minute/1.73m2 either measured or calculated using a standard Cockcroft and Gault formula (Cockroft and Gault, 1976, Appendix A)."}
• {"criterion_text":"- 10.\tFemales of childbearing potential (FCBP) must not be pregnant or breastfeeding and must agree to use two effective contraception methods (at least one highly-effective method and one additional acceptable (barrier) method, see Appendix G) each time engaging in sexual activity with a male during the study treatment and for 12 months following the last dose of treatment. FCBP must refrain from donating oocyte during the course of study or for 12 months following the last dose of treatment, whichever is longer."}
• {"criterion_text":"- 11.\tMale participants must agree to use condom each time they have sex with a woman of childbearing potential during the study treatment and for 6 months following the last dose of treatment. In addition to the use of condom by male participants, their female partners who are of childbearing potential must use one highly effective contraception method (see Appendix G) at the same time. Male participants must refrain from donating sperm during the study participation or for 6 months following the last dose of treatment, whichever is longer."}
• {"criterion_text":"- 12.\tIn the opinion of investigator, the patient must: a.\tbe able to understand, give written informed consent, and comply with all study-related procedures, medication use, and evaluations b.\tnot have a history of noncompliance in relation to medical regimens or be considered potentially unreliable and/or uncooperative"}

Exclusion criteria

• {"criterion_text":"- Patients must be excluded from participating in this clinical trial if they meet any of the following criteria: 1.\tCurrent diagnosis of any following lymphomas: a.\tPrimary cutaneous CD30-positive T-cell lymphoproliferative disorders and lymphomas. Cutaneous ALCL with extracutaneous tumour spread beyond locoregional lymph nodes is eligible (previous single-agent treatment to address cutaneous and locoregional disease is permissible) b.\tMycosis fungoides (MF), including transformed MF c.\tPTCL CD30-negative"}
• {"criterion_text":"- 2.\tHistory of another primary invasive cancer, hematologic malignancy, or myelodysplastic syndrome that has not been in remission for at least 3 years. Exceptions are malignancies with a negligible risk of metastasis or death (e.g., 5-year OS ≥90%), such as carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer."}
• {"criterion_text":"- 3.\tHistory of progressive multifocal leukoencephalopathy (PML)."}
• {"criterion_text":"- 4.\tKnown central nervous system (CNS) lymphoma involvement"}
• {"criterion_text":"- 5.\tPrior treatment with brentuximab vedotin."}
• {"criterion_text":"- 6.\tBaseline peripheral neuropathy ≥Grade 2 (per the NCI CTCAE, Version 5.0)"}
• {"criterion_text":"- 7.\tLeft ventricular ejection fraction (LVEF) of < 45% or history of myocardial infarction ≤6 months, or symptomatic cardiac disease (including symptomatic ventricular dysfunction, symptomatic coronary artery disease, and symptomatic arrhythmias) or prior treatment with anthracyclines."}
• {"criterion_text":"- 8.\tAny uncontrolled Grade 3 or higher (per the National Cancer Institute’s Common Terminology Criteria for Adverse Events, NCI CTCAE Version 5.0) viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study treatment."}
• {"criterion_text":"- 9.\tKnown human immunodeficiency virus (HIV) infection, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection."}
• {"criterion_text":"- 10.\tHistory of hypersensitivity to any component of CHEP, to compounds of similar biological or chemical composition as brentuximab vedotin, and/or the excipients contained in any of the drug formulations of study treatment."}
• {"criterion_text":"- 11.\tFemales who are pregnant or breastfeeding"}
• {"criterion_text":"- 12.\tPlanned CNS prophylaxis with intravenous high-dose methotrexate."}
• {"criterion_text":"- 13.\tVaccination with live vaccine within 30 days prior to study treatment"}
• {"criterion_text":"- 14.\tAny contraindication for brentuximab vedotin, cyclophosphamide, doxorubicin, etoposide or prednisone according to the respective SmPCs."}
• {"criterion_text":"- 15.\tSevere hepatic or renal impairment."}

Primary endpoints

• {"endpoint_text":"- Primary Endpoint 1.\tPET-negative complete response (CR) rate at the end of treatment","definition_or_measurement_approach":"Assessment based on PET negativity; main objective states efficacy is assessed based on Lugano 2014 criteria."}

Secondary endpoints

• {"endpoint_text":"- Key Secondary Endpoints 2.\tType, incidence, severity, seriousness, and relatedness of treatment emergent adverse events.","definition_or_measurement_approach":"Safety assessed by recording type, incidence, severity, seriousness, and relatedness of treatment-emergent adverse events (per NCI CTCAE v5.0 where applicable)."}
• {"endpoint_text":"- Key Secondary Endpoints 3.\tType, incidence, severity, seriousness, and relatedness of adverse events in the follow-up period.","definition_or_measurement_approach":"Adverse events in the follow-up period recorded and assessed for type, incidence, severity, seriousness and relatedness."}
• {"endpoint_text":"- Secondary Endpoints 1.\tProgression-free survival (PFS)","definition_or_measurement_approach":"PFS measured per trial definitions (based on Lugano 2014 criteria as referenced)."}
• {"endpoint_text":"- Secondary Endpoints 2.\tOverall survival (OS)","definition_or_measurement_approach":"OS measured from randomisation/enrolment to death from any cause."}
• {"endpoint_text":"- Secondary Endpoints 3.\tEvent-free survival (EFS)","definition_or_measurement_approach":"EFS measured per protocol definitions (events include progression, relapse, or death as defined)."}
• {"endpoint_text":"- Secondary Endpoints 4.\tObjective Response Rate (ORR) at the end of treatment","definition_or_measurement_approach":"ORR assessed per Lugano 2014 criteria (overall response rates including CR and PR)."}
• {"endpoint_text":"- Secondary Endpoints 5.\tRate of pre-planned upfront HDT/ASCT","definition_or_measurement_approach":"Proportion of patients undergoing pre-planned high-dose therapy with ASCT after study treatment."}
• {"endpoint_text":"- Secondary Endpoints 6.\tDuration of response (DoR)","definition_or_measurement_approach":"DoR measured from first documented response until progression or death per protocol."}

Other endpoints

• {"endpoint_text":"- Exploratory Objective 1.\tTo evaluate residual disease burden by serial ctDNA assessment","definition_or_measurement_approach":"Serial circulating tumor DNA (ctDNA) measurements to describe residual disease burden over time."}
• {"endpoint_text":"- Exploratory Objective 2.\tTo analyse mutational profile from tumour tissue by targeted next-generation DNA sequencing and to correlate it with mutational profile of ctDNA","definition_or_measurement_approach":"Targeted NGS on tumour tissue and comparison/correlation with ctDNA mutational profiles."}
• {"endpoint_text":"- Exploratory Objective 3.\tTo assess the relationship between potential molecular or cellular markers and efficacy brentuximab vedotin in combination with CHEP.","definition_or_measurement_approach":"Correlation analyses between specified molecular/cellular markers and efficacy endpoints (e.g., CR, PFS)."}

Czechia

Earliest CTIS Part Ii Submission Date

08-08-2024

Latest Decision Or Authorization Date

27-08-2024

Processing Time Days

19

Number Of Sites

7

Number Of Participants

33

Primary sponsor

Full Name

Kooperativni Lymfomova Skupina z.s.

Organisation Type

Patient organisation/association

Country Of Registered Address

Czechia