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Clinical Trial Details

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Hematological Malignancies

Brentuximab vedotin

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
Phase 2
NCT04569032

Active Not-enrolling

Globe
Locations

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

Study design

Participant Group/Arm

EXPERIMENTAL: CD30-negative Cohort

Participants with CD30 expression level \< 1%

Intervention/Treatment

DRUG: brentuximab vedotin

1.8 mg/kg administered intravenously (IV; into the vein) on Day 1 of each 21 -day cycle

DRUG: cyclophosphamide

750 mg/m\^2 administered intravenously (IV; into the vein) on Day 1 of each 21 -day cycle

DRUG: doxorubicin

50 mg/m\^2 administered intravenously (IV; into the vein) on Day 1 of each 21 -day cycle

DRUG: prednisone

100 mg daily administered orally on Days 1-5 of each cycle

Participant Group/Arm

EXPERIMENTAL: CD30-positive Cohort

Participants with CD30 expression level ≥1% to \< 10%

Intervention/Treatment

DRUG: brentuximab vedotin

1.8 mg/kg administered intravenously (IV; into the vein) on Day 1 of each 21 -day cycle

DRUG: cyclophosphamide

750 mg/m\^2 administered intravenously (IV; into the vein) on Day 1 of each 21 -day cycle

DRUG: doxorubicin

50 mg/m\^2 administered intravenously (IV; into the vein) on Day 1 of each 21 -day cycle

DRUG: prednisone

100 mg daily administered orally on Days 1-5 of each cycle

Key eligibility criteria

Inclusion criteria

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) phenoty
  • 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
  • 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.
Exclusion criteria

Exclusion Criteria

  • Current diagnosis of any of the following:
    • sALCL
    • Primary cutaneous T-cell lymphoproliferative disorders and lymphomas
    • Mycosis fungoides (MF), including transformed
  • 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.

Key dates

Study start date
  • November 2020
Estimated primary completion date
  • September 2024

Key endpoints

Primary Outcome Measures
Outcome Measure

Objective response rate (ORR) per blinded independent central review (BICR) using Revised Response Criteria for Malignant Lymphoma criteria (Cheson 2007)

Measure Description

ORR is defined as the proportion of participants with complete response (CR) or partial response (PR) at the completion of study treatment

Time Frame

From start of study treatment up to approximately 7 months

Secondary Outcome Measures:
Outcome Measure

Complete response (CR) rate per BICR

Measure Description

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).

Time Frame

From start of study treatment up to approximately 7 months

Outcome Measure

Progression-free survival (PFS) per BICR

Measure Description

Time from start of treatment to the first documented disease progression or death from any cause, whichever comes first

Time Frame

Up to approximately 3 years

Outcome Measure

Overall survival

Measure Description

Time from first dose to death due to any cause

Time Frame

Up to approximately 3 years

Outcome Measure

Duration of response (DOR) per BICR

Measure Description

Time from first occurrence of an objective response to the date of disease progression or death from any cause, whichever comes first

Time Frame

Approximately 3 years

Outcome Measure

ORR per BICR per modified Lugano criteria (Cheson 2014)

Measure Description

ORR is defined as the proportion of participants with CR or PR at the completion of study treatment

Time Frame

From start of study treatment up to approximately 7 months

Outcome Measure

Incidence of adverse events

Measure Description

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

Time Frame

From start of study treatment up to approximately 7 months

Outcome Measure

Incidence of laboratory abnormalities

Measure Description

To be summarized using descriptive statistics.

Time Frame

From start of study treatment up to approximately 7 months

Number of participants

82

Collaborators and investigators

Sponsor: Seagen Inc.

Collaborator: None

This information is current as of February 20th 2024.