A Study of Brentuximab Vedotin and CHP in Frontline Treatment of PTCL With Less Than 10% CD30 Expression

Peripheral T-cell Lymphoma Clinical Trial

Official title:

A Dual-cohort, Open-label, Phase 2 Study of Brentuximab Vedotin and CHP (A+CHP) in the Frontline Treatment of Subjects With Peripheral T-cell Lymphoma (PTCL) With Less Than 10% CD30 Expression

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04569032
• Other study ID #: SGN35-032
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 12, 2020
• Est. completion date: September 30, 2024

Study information

• Verified date: June 2024
• Source: Seagen Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This clinical trial will study brentuximab vedotin with CHP to find out if the drugs work for people who have certain types of peripheral T-cell lymphoma (PTCL). It will also find out what side effects occur when brentuximab vedotin and CHP are used together. A side effect is anything the drugs do besides treating cancer. CHP is a type of chemotherapy that uses three drugs (cyclophosphamide, doxorubicin, and prednisone). CHP is approved by the FDA to treat certain types of PTCL.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 82
• Est. completion date: September 30, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Newly diagnosed PTCL, excluding systemic anaplastic large cell lymphoma (sALCL), per the Revised European-American Lymphoma World Health Organization (WHO) 2016 classification

• The following non-sALCL PTCL subtypes are eligible:

• PTCL - not otherwise specified (PTCL-NOS)

• Angioimmunoblastic T-cell lymphoma (AITL)

• Adult T-cell leukemia/lymphoma (ATLL; acute and lymphoma types only, must be positive for human T cell leukemia virus 1)

• Enteropathy-associated T-cell lymphoma (EATL)

• Hepatosplenic T-cell lymphoma

• Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITCL)

• Indolent T-cell lymphoproliferative disorder (T-LPD) of the gastrointestinal (GI) tract

• Follicular T-cell lymphoma

• Nodal peripheral T-cell lymphoma with T-follicular helper (TFH) phenotype

• CD30 expression <10% by local assessment in tumor containing lymph node or other extranodal soft tissue biopsy

• Fluorodeoxyglucose (FDG)-avid disease by PET and measurable disease of at least 1.5 cm by CT, as assessed by the site radiologist

• An Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2

Exclusion Criteria

• Current diagnosis of any of the following:

• sALCL

• Primary cutaneous T-cell lymphoproliferative disorders and lymphomas

• Mycosis fungoides (MF), including transformed MF

• 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.

• History of progressive multifocal leukoencephalopathy (PML).

• Cerebral/meningeal disease related to the underlying malignancy.

• Prior treatment with brentuximab vedotin or doxorubicin.

• Baseline peripheral neuropathy Grade 2 or higher (per the NCI CTCAE, Version 4.03) or subjects with the demyelinating form of Charcot-Marie-Tooth syndrome.

• Left ventricular ejection fraction less than 45% or symptomatic cardiac disease (including symptomatic ventricular dysfunction, symptomatic coronary artery disease, and symptomatic arrhythmias), or myocardial infarction within the past 6 months, or previous treatment with complete cumulative dose of >300 mg/m2 of doxorubicin.

• Any uncontrolled Grade 3 or higher (per the National Cancer Institute's Common Terminology Criteria for Adverse Events, NCI CTCAE Version 4.03) viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study drug. Routine antimicrobial prophylaxis is permitted.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• Peripheral T-cell Lymphoma

Intervention

Drug:
• brentuximab vedotin
1.8 mg/kg administered intravenously (IV; into the vein) on Day 1 of each 21 -day cycle
• cyclophosphamide
750 mg/m^2 administered intravenously (IV; into the vein) on Day 1 of each 21 -day cycle
• doxorubicin
50 mg/m^2 administered intravenously (IV; into the vein) on Day 1 of each 21 -day cycle
• prednisone
100 mg daily administered orally on Days 1-5 of each cycle

Locations

Country	Name	City	State
Czechia	Fakultni Nemocnice Ostrava	Ostrava - Poruba	Other
Czechia	Fakultni Nemocnice Kralovske Vinohrady	Praha 10	Other
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2	Other
France	CHD Vendee, Site de La Roche-sur-Yon, Les Oudairies	Cedex 9	Other
France	Centre Hospitalier Universitaire de Grenoble	La Tronche	Other
France	Hopital Emile Muller	Mulhouse	Other
France	Groupe Hospitalier du Haut Leveque	Pessac	Other
France	Centre Hospitalier Lyon Sud	Pierre Benite Cedex	Other
France	Centre Henri Becquerel / Centre Regional de Lutte Contre le Cancer	Rouen	Other
Italy	Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi	Bologna	Other
Italy	Azienda Ospedaliera Spedali Civili di Brescia	Brescia	Other
Italy	Candiolo Cancer Institute, FPO-IRCCS	Candiolo (Torino)	Other
Italy	A.O.U Policlinico G. Rodolico S. Marco	Catania	Other
Italy	Azienda Ospedaliera Universitaria San Martino	Genova	Other
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano
Italy	IRCSS Policlinico San Matteo	Pavia	Other
Italy	Azienda Ospedaliera Universitaria Integrata di Verona	Verona	Other
Spain	Hospital de la Santa Creu i Sant Paul	Barcelona	Other
Spain	L'Institut Catala d'Oncologia	L'Hospitalet de Llobregat	Other
Spain	Hospital Universitario 12 de Octubre	Madrid	Other
Spain	Hospital Universitario La Paz	Madrid	Other
Spain	MD Anderson Cancer Center - Madrid	Madrid	Other
Spain	Hospital Costa del Sol	Marbella	Other
Spain	Hospital Clinico Universitario de Salamanca	Salamanca	Other
Spain	Hospital Universitario Virgen del Rocio	Sevilla	Other
United Kingdom	The Beatson West of Scotland Cancer Centre	Glasgow	Other
United Kingdom	Oxford University Hospitals	Headington	Other
United Kingdom	Imperial College Healthcare NHS Trust	London	Other
United Kingdom	The Royal Marsden Hospital	London	Other
United Kingdom	University College London Hospitals NHS Foundation Trust	London	Other
United Kingdom	Christie Hospital NHS Foundation Trust	Manchester	Other
United Kingdom	The Royal Marsden Hospital (Surrey)	Sutton	Other
United States	Texas Oncology - Amarillo	Amarillo	Texas
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Rocky Mountain Cancer Centers - Aurora	Aurora	Colorado
United States	Texas Oncology - Austin Midtown	Austin	Texas
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Cleveland Clinic, The	Cleveland	Ohio
United States	Oncology Hematology Care	Fairfield	Ohio
United States	Texas Oncology - Fort Worth 12th Avenue	Fort Worth	Texas
United States	MD Anderson Cancer Center / University of Texas	Houston	Texas
United States	University of Tennessee	Knoxville	Tennessee
United States	Texas Oncology - Northeast Texas	Longview	Texas
United States	Ochsner Medical Center	New Orleans	Louisiana
United States	Tulane University Hospital and Clinic	New Orleans	Louisiana
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Illinois Cancer Specialists	Niles	Illinois
United States	Virginia Commonwealth University Medical Center	Richmond	Virginia
United States	Stanford Cancer Center / Blood and Marrow Transplant Program	Stanford	California
United States	Virginia Oncology Associates - Virginia Beach	Virginia Beach	Virginia
United States	Johns Hopkins Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Seagen Inc.

Countries where clinical trial is conducted

United States,  Czechia,  France,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR) per blinded independent central review (BICR) using Revised Response Criteria for Malignant Lymphoma criteria (Cheson 2007)	ORR is defined as the proportion of participants with complete response (CR) or partial response (PR) at the completion of study treatment	From start of study treatment up to approximately 7 months
Secondary	Complete response (CR) rate per BICR	CR rate is defined as the proportion of participants with CR following the completion of study treatment using Revised Response Criteria of Malignant Lymphoma (Cheson 2007).	From start of study treatment up to approximately 7 months
Secondary	Progression-free survival (PFS) per BICR	Time from start of treatment to the first documented disease progression or death from any cause, whichever comes first	Up to approximately 3 years
Secondary	Overall survival	Time from first dose to death due to any cause	Up to approximately 3 years
Secondary	Duration of response (DOR) per BICR	Time from first occurrence of an objective response to the date of disease progression or death from any cause, whichever comes first	Approximately 3 years
Secondary	ORR per BICR per modified Lugano criteria (Cheson 2014)	ORR is defined as the proportion of participants with CR or PR at the completion of study treatment	From start of study treatment up to approximately 7 months
Secondary	Incidence of adverse events	An adverse event is any untoward medical occurrence in a subject or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment	From start of study treatment up to approximately 7 months
Secondary	Incidence of laboratory abnormalities	To be summarized using descriptive statistics.	From start of study treatment up to approximately 7 months