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

Seagen

Status and phase: Active, not recruiting; Phase 2

Conditions: Peripheral T-cell Lymphoma

Treatments: Drug: doxorubicin; Drug: prednisone; Drug: cyclophosphamide; Drug: brentuximab vedotin

Study type: Interventional

Funder types: Industry

Identifiers

NCT04569032

SGN35-032

Details and patient eligibility

About

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.

Enrollment: 82 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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) 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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82 participants in 2 patient groups

CD30-negative Cohort

Experimental group

Description:

Participants with CD30 expression level \< 1%

Treatment:

Drug: brentuximab vedotin

Drug: prednisone

Drug: cyclophosphamide

Drug: doxorubicin

CD30-positive Cohort

Experimental group

Description:

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

Treatment:

Drug: brentuximab vedotin

Drug: prednisone

Drug: cyclophosphamide

Drug: doxorubicin