The standard of care for patients with newly diagnosed CD30-positive PTCL is treatment with a combination of drugs called CHOP. This study is conducted to improve the effectiveness of CHOP chemotherapy with combination therapy, in which vincristine is replaced by brentuximab vedotin. Also, the addition of etoposide to various chemotherapy regimens for T-lymphomas has been associated with promising results in several other studies. This combination is called A + CHEP.
- Conditions
- Peripheral T-cell lymphomas (PTCL)MedDRA version: 20.0Level: HLTClassification code 10002450Term: Angioimmunoblastic T-cell lymphomasSystem Organ Class: 100000004851MedDRA version: 20.0Level: HLTClassification code 10001414Term: Adult T-cell lymphomas/leukaemiasSystem Organ Class: 100000004851MedDRA version: 20.0Level: HLTClassification code 10022704Term: Intestinal T-cell lymphomasSystem Organ Class: 100000004851MedDRA version: 20.0Level: HLTClassification code 10034622Term: Peripheral T-cell lymphomas NECSystem Organ Class: 100000004851MedDRA version: 21.0Level: LLTClassification code 10002451Term: Angioimmunoblastic T-cell lymphoma NOSSystem Organ Class: 100000004864MedDRA version: 21.0Level: LLTClassification code 10001415Term: Adult T-cell lymphoma/leukaemia NOSSystem Organ Class: 100000004864MedDRA version: 21.1Level: LLTClassification code 10076434Term: Hepatosplenic gamma-delta T-cell lymphomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2021-003526-80-CZ
- Lead Sponsor
- Kooperativní lymfomová skupina, z.s.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 33
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 >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
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method