A Phase II Open Label Study of Brentuximab Vedotin in Combination with CHEP in Patients with Previously Untreated CD30-expressing Peripheral T-cell Lymphomas (PTCL)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Kooperativni Lymfomova Skupina z.s.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02], Diseases [C] - Hemic and Lymphatic Diseases [C15]

Decision date (initial)

2024-08-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-511567-28-01

EudraCT number

2021-003526-80

ClinicalTrials.gov

NCT05006664

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

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 objectives 1

1. 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.

Conditions and MedDRA coding

Cancer

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 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 < 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. Alanine transaminase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) ≤3 × ULN, or <5 × ULN in cases of documented liver involvement by lymphoma e. Serum 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). 10. Females 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. 11. Male 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. 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 uncooperative

Exclusion criteria 1

1. Patients must be excluded from participating in this clinical trial if they meet any of the following 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. 15. Severe hepatic or renal impairment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary Endpoint 1. PET-negative complete response (CR) rate at the end of treatment

Secondary endpoints 1

1. 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. Descript

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Kooperativni Lymfomova Skupina z.s.

Sponsor organisation

Kooperativni Lymfomova Skupina z.s.

Address

U Nemocnice 449/2, Nove Mesto Nove Mesto

City

Prague

Postcode

128 00

Country

Czechia

Scientific contact point

Organisation

Kooperativni Lymfomova Skupina z.s.

Contact name

prof. MUDr. Marek Trneny, CSc.

Public contact point

Organisation

Kooperativni Lymfomova Skupina z.s.

Contact name

prof. MUDr. Marek Trneny, CSc.

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications