Peripheral T-cell lymphomas (PTCL) MedDRA version: 20.0 Level: HLT Classification code 10002450 Term: Angioimmunoblastic T-cell lymphomas System Organ Class: 100000004851 MedDRA version: 20.0 Level: HLT Classification code 10001414 Term: Adult T-cell lymphomas/leukaemias System Organ Class: 100000004851 MedDRA version: 20.0 Level: HLT Classification code 10022704 Term: Intestinal T-cell lymphomas System Organ Class: 100000004851 MedDRA version: 20.0 Level: HLT Classification code 10034622 Te
Conditions
Interventions
Trade Name: Adcetris
Product Name: Adcetris
Product Code: Kód SÚKL 0193650
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Brentuximab vedotin
CAS Number: 91
Sponsors
Kooperativní lymfomová skupina, z.s.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age >18 years 2. Written informed consent 3. Histologically 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. Systemic anaplastic large cell lymphoma (ALCL) ALK+ with age- adjusted international prognostic index (aaIPI) =1 b. Systemic anaplastic large cell lymphoma (ALCL) ALK- c. Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) d. Angioimmunoblastic T-cell lymphoma (AITL) e. Adult T-cell leukaemia/lymphoma (ATLL; acute and lymphoma types only, must be positive for human T cell leukaemia virus 1) f. Enteropathy-associated T-cell lymphoma (EATL) g. Hepatosplenic T-cell lymphoma h. Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITCL) i. Indolent T-cell lymphoproliferative disorder (T-LPD) of the gastrointestinal (GI) tract j. Follicular T-cell lymphoma k. Nodal peripheral T-cell lymphoma with T-follicular helper (TFH) phenotype 4. Positive CD30 expression by local pathology assessment. 5. Patients 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. 6. Eastern Cooperative Oncology Group (ECOG, Appendix B) performance status of 0 to 1 7. Patient must be autologous stem cell transplant (ASCT)-eligible 8. Patient must be appropriate candidate for treatment with anthracyclines 9. Patient must have the following laboratory criteria at screening: a. Absolute neutrophil count (ANC) = 1.0 x 109/L (unless secondary to bone marrow involvement by PTCL) b. Platelet count = 50 x 109/L (unless secondary to bone marrow involvement by PTCL) c. Total serum bilirubin 40 mL/minute/1.73m2 either measured or calculated using a standard Cockcroft and Gault formula (Cockroft and Gault, 1976, Appendix A) and serum creatinine must be <175 µmol/L.10. 10. Females of childbearing potential (FCBP) must not be pregnant or breastfeeding and must agree to use at least two effective contraception method during the study and for 6 months following the last dose of treatment. 11. Male participants must: Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 6 months following the last dose of treatment. 12. In the opinion of investigator, the patient must: a. be able to understand, give written informed consent, and comply with all study-related procedures, medication use, and evaluations b. not have a history of noncompliance in relation to medical regimens or be considered potentially unreliable and/or uncooperat
Exclusion criteria
Exclusion criteria: 1. Current diagnosis of any following lymphomas: a. Primary 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. Mycosis fungoides (MF), including transformed MF c. PTCL CD30-negative 2. History 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. 3. History of progressive multifocal leukoencephalopathy (PML). 4. Known central nervous system (CNS) lymphoma involvement 5. Prior treatment with brentuximab vedotin. 6. Baseline peripheral neuropathy =Grade 2 (per the NCI CTCAE, Version 5.0) 7. Left 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. 8. Any 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. 9. Known human immunodeficiency virus (HIV) infection, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection. 10. History 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. 11. Females who are pregnant or breastfeeding 12. Planned CNS prophylaxis with intravenous high-dose methotrexate. 13. Vaccination with live vaccine within 30 days prior to study treatment 14. Any contraindication for brentuximab vedotin, cyclophosphamide, doxorubicin, etoposide or prednisone according to the respective SmPCs.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective To assess efficacy (based on Lugano 2014 criteria) of brentuximab vedotin in combination with CHEP. Key Secondary Objective To assess safety and tolerability of brentuximab vedotin in combination with CHEP. Secondary Objective To assess efficacy (based on Lugano 2014 criteria) of brentuximab vedotin in combination with CHEP. Exploratory Objectives 1.To evaluate residual disease burden by serial ctDNA assessment 2.To analyse mutational profile from tumour tissue by targeted next- generation DNA sequencing and to correlate it with mutational profile of ctDNA 3.To assess the relationship between potential molecular or cellular markers and efficacy brentuximab vedotin in combination with CHEP. ;Secondary Objective: Key Secondary Objective To assess safety and tolerability of brentuximab vedotin in combination with CHEP. Secondary Objective To assess efficacy (based on Lugano 2014 criteria) of brentuximab vedotin in combination with CHEP. ;Primary end point(s): Primary Endpoint 1.PET-negative complete response (CR) rate at the end of treatment Key Secondary Endpoints 2.Type, incidence, severity, seriousness, and relatedness of treatment emergent adverse events. 3.Type, incidence, severity, seriousness, and relatedness of adverse events in the follow-up period. Secondary Endpoints 1.Progression-free survival (PFS) 2.Overall survival (OS) 3. Event-free survival (EFS) 4. Objective Response Rate (ORR) at the end of treatment 5. Rate of pre-planned upfront HDT/ASCT 6. Duration of response (DoR) Exploratory Endpoints 1.Descriptive statistics of ctDNA by visit. 2.Correlation of tumour tissue mutational profile with ctDNA mutational profile 3.The relationship of the following endpoints may be assessed for the following markers: Endpoints, e.g.: 1.PET-negative CR rate at the end of treatment 2.ORR at the end of treatment 3.PFS 4.EFS 5.DoR Markers, e.g.: 1.Semi-quantit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Endpoints 2. Type, incidence, severity, seriousness, and relatedness of treatment emergent adverse events. 3. Type, incidence, severity, seriousness, and relatedness of adverse events in the follow-up period. Secondary Endpoints 1. Progression-free survival (PFS) 2. Overall survival (OS)Event-free survival (EFS) 4. Objective Response Rate (ORR) at the end of treatment 5. Rate of pre-planned upfront HDT/ASCT 6. Duration of response (DoR) ;Timepoint(s) of evaluation of this end point: Efficacy will be evaluated in terms of CR rate, ORR, PFS, EFS, OS, DoR. Imaging assessment of efficacy/disease response will be recorded at the end of cycle 3 and after the end of treatment (1-14 days after day 21 of the last treatment cycle the patient started) as well as in pre-defined timepoints during the FU period. PET/CT must be used at screening and at end of treatment visit, CT or MRI may be used in other pre-defined timepoints. The safety and tolerability of study treatment will be evaluated by means of AE reports (nature, severity, frequency, causality), performance status, physical examinations, ECG and laboratory safety evaluations. | — |
Countries
Czechia, Czech Republic
Contacts
Public ContactMgr. Veronika Nováková
Kooperativní lymfomová skupina, z.s.
Outcome results
None listed