Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma

NCT ID: NCT03113500

Last Updated: 2025-11-14

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-05-25

Study Completion Date

2026-07-07

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This phase II trial studies the side effects and how well brentuximab vedotin and combination chemotherapy work in treating patients with CD30-positive peripheral T-cell lymphoma. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, etoposide, and prednisone work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving brentuximab vedotin and combination chemotherapy may work better in treating patients with CD30-positive peripheral T-cell lymphoma.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

PRIMARY OBJECTIVES:

I. Assess the safety and tolerability of cyclophosphamide, doxorubicin hydrochloride (doxorubicin), etoposide phosphate (etoposide), prednisone, and brentuximab vedotin (CHEP-BV), as induction therapy in patients with CD30-positive peripheral T-cell lymphoma (PTCL). (Safety lead-in) II. Assess the anti-lymphoma activity of CHEP-BV as induction treatment in patients with CD30-positive PTCL. (Phase 2)

SECONDARY OBJECTIVES:

I. Describe outcomes of CD30-positive PTCL patients who go on to receive BV consolidation therapy post CHEP-BV induction with/without autologous hematopoietic cell transplantation/radiation.

EXPLORATORY OBJECTIVES:

I. Explore the rate of minimal residual disease (MRD) negativity (as assessed by next-generation sequencing) and MRD kinetics after CHEP-BV and BV consolidation therapy in CD30-positive PTCL.

II. Explore the possible association between outcome after study treatment and CD30 expression, gene expression profiles (GEP), and genetic mutations as measured in PTCL tumor samples.

OUTLINE:

INDUCTION: Patients receive cyclophosphamide intravenously (IV) and doxorubicin IV on day 1, etoposide IV on days 1-3, and prednisone orally (PO) on days 1-5. Patients also receive brentuximab vedotin IV over approximately 30 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles (or for up to 5 cycles for patients who received 1 cycle of cyclophosphamide, doxorubicin, vincristine and prednisone \[CHOP\]-like or brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone \[CHP-BV\] therapy prior to induction, per investigator's discretion) in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Between 30-60 days post-consolidative autologous stem cell therapy, post-consolidative radiation therapy, or after completing induction cycle 6 (cycle 5 for patients who qualify for receiving 5 cycles of CHEP-BV instead of 6), patients with objective response (complete response or partial response) receive brentuximab vedotin IV over approximately 30 minutes on day 1. Treatment repeats every 21 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, 6 months, and 12 months.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Adult T-Cell Leukemia/Lymphoma Anaplastic Large Cell Lymphoma, ALK-Negative Anaplastic Large Cell Lymphoma, ALK-Positive Angioimmunoblastic T-Cell Lymphoma Ann Arbor Stage II Noncutaneous Anaplastic Large Cell Lymphoma Ann Arbor Stage III Noncutaneous Anaplastic Large Cell Lymphoma Ann Arbor Stage IV Noncutaneous Anaplastic Large Cell Lymphoma Enteropathy-Associated T-Cell Lymphoma Hepatosplenic T-Cell Lymphoma Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma, Not Otherwise Specified

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Treatment (CHEP-BV)

INDUCTION: Patients receive cyclophosphamide IV and doxorubicin IV on day 1, etoposide IV on days 1-3, and prednisone PO on days 1-5. Patients also receive brentuximab vedotin IV over approximately 30 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles (or for up to 5 cycles for patients who received 1 cycle of CHOP-like or CHP-BV therapy prior to induction, per investigator's discretion) in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Between 30-60 days post-consolidative autologous stem cell therapy, post-consolidative radiation therapy, or after completing induction cycle 6 (cycle 5 for patients who qualify for receiving 5 cycles of CHEP-BV instead of 6), patients with objective response (complete response or partial response) receive brentuximab vedotin IV over approximately 30 minutes on day 1. Treatment repeats every 21 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Brentuximab Vedotin

Intervention Type DRUG

Given IV

Cyclophosphamide

Intervention Type DRUG

Given IV

Doxorubicin

Intervention Type DRUG

Given IV

Doxorubicin Hydrochloride

Intervention Type DRUG

Given IV

Etoposide

Intervention Type DRUG

Given IV

Etoposide Phosphate

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Prednisone

Intervention Type DRUG

Given PO

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Brentuximab Vedotin

Given IV

Intervention Type DRUG

Cyclophosphamide

Given IV

Intervention Type DRUG

Doxorubicin

Given IV

Intervention Type DRUG

Doxorubicin Hydrochloride

Given IV

Intervention Type DRUG

Etoposide

Given IV

Intervention Type DRUG

Etoposide Phosphate

Given IV

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Prednisone

Given PO

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

ADC SGN-35 Adcetris Anti-CD30 Antibody-Drug Conjugate SGN-35 Anti-CD30 Monoclonal Antibody-MMAE SGN-35 Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35 cAC10-vcMMAE SGN-35 (-)-Cyclophosphamide 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate Carloxan Ciclofosfamida Ciclofosfamide Cicloxal Clafen Claphene CP monohydrate CTX CYCLO-cell Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Cyclophosphamide Monohydrate Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR- 138719 Adriablastin Hydroxydaunomycin Hydroxyl Daunorubicin Hydroxyldaunorubicin 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI) ADM Adriacin Adriamycin Adriamycin Hydrochloride Adriamycin PFS Adriamycin RDF ADRIAMYCIN, HYDROCHLORIDE Adriamycine Adriblastina Adriblastine Adrimedac Chloridrato de Doxorrubicina DOX DOXO-CELL Doxolem Doxorubicin HCl Doxorubicin.HCl Doxorubin Farmiblastina FI 106 FI-106 hydroxydaunorubicin Rubex Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16 VP 16-213 VP-16 VP-16-213 VP16 Etopophos .delta.1-Cortisone 1, 2-Dehydrocortisone Adasone Cortancyl Dacortin DeCortin Decortisyl Decorton Delta 1-Cortisone Delta-Dome Deltacortene Deltacortisone Deltadehydrocortisone Deltasone Deltison Deltra Econosone Lisacort Meprosona-F Metacortandracin Meticorten Ofisolona Orasone Panafcort Panasol-S Paracort Perrigo Prednisone PRED Predicor Predicorten Prednicen-M Prednicort Prednidib Prednilonga Predniment Prednisone Intensol Prednisonum Prednitone Promifen Rayos Servisone SK-Prednisone

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Documented informed consent of participant and/or legally authorized representative
* Agreement to allow the use of archival tissue from diagnostic tumor biopsies will be retrieved and submitted post-enrollment

* If unavailable, exceptions may be granted with study principal investigator (PI) approval.
* Eastern Cooperative Oncology Group (ECOG) status =\< 2
* Histologically confirmed mature peripheral T-cell or natural killer (NK)-cell lymphoma per World Health Organization (WHO) classification, including:

* Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) with international protein index (IPI) of 2 or higher (must have bulky \[defined as mass \>= 10 cm\] stage II, or stage III-IV disease)
* ALK-negative ALCL

* NOTE: Per amendment dated 05-10-19, ALCL will no longer be eligible except for Canada.
* PTCL-not otherwise specified (NOS)
* Angioimmunoblastic T-cell lymphoma (AITL)
* Adult T-cell lymphoma/leukemia (ATLL)
* Enteropathy-associated T-cell lymphoma (EATL)
* Hepatosplenic T-cell lymphoma
* CD30-positivity (e.g. at least 1%) by immunohistochemistry confirmed by hematopathology review at the participating institution
* Measurable disease of at least 1.5 cm on computed tomography (CT) or positron emission tomography (PET)-CT scan
* Absolute neutrophil count (ANC) \>= 1,000/mm\^3

* Exception: unless documented bone marrow involvement by lymphoma
* Platelets \>= 50,000/mm\^3

* Exception: unless documented bone marrow involvement by lymphoma
* Total serum bilirubin =\< 1.5 x upper limit of normal (ULN) OR if hepatic involvement by lymphoma: =\< 3 x ULN for Gilbert's disease or documented hepatic involvement by lymphoma
* Aspartate aminotransferase (AST) =\< 2 x ULN OR if hepatic involvement by lymphoma: AST =\< 5 x ULN
* Alanine aminotransferase (ALT) =\< 2 x ULN OR if hepatic involvement by lymphoma: ALT =\< 5 x ULN
* Creatinine clearance of \>= 60 mL/min per the Cockcroft-Gault formula
* Left ventricular ejection fraction (LVEF) \>= 45%
* Women of childbearing potential (WOCBP): negative urine or serum pregnancy test; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* Agreement by WOCBP and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy; childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)

Exclusion Criteria

* Prior treatment of PTCL with systemic anti-lymphoma therapies, investigational agents, radiation

* Exception: May have received 1 cycle of CHOP-like therapy (e.g. CHOP, CHOEP, EPOCH) or 1 cycle of CHP-BV; these participants must initiate day 1 cycle 1 of study therapy (CHEP-BV) no less than 19 days from prior CHOP-like or CHP-BV therapy; Patients who received 1 cycle of CHOP-like or 1 cycle of CHP-BV therapy prior to initiating induction with CHEP-BV are allowed to receive only 5 cycles of CHEP-BV instead of 6 cycles, per investigator's discretion
* History of another primary invasive cancer, hematologic malignancy, or myelodysplastic syndrome that has not been in remission for at least 3 years.

* Exceptions: Non-melanoma skin cancer and in situ cervical cancer
* Symptomatic cardiac disease (including symptomatic ventricular dysfunction, symptomatic coronary artery disease, and symptomatic arrhythmias), cerebrovascular event/stroke or myocardial infarction within the past 6 months
* Central nervous system involvement by lymphoma, including leptomeningeal involvement
* History of progressive multifocal leukoencephalopathy (PML)
* Active \>= grade 3 viral, bacterial, or fungal infection within 2 weeks prior to day 1 of protocol therapy
* Any known human immunodeficiency virus (HIV) infection, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
* Baseline peripheral neuropathy \>= grade 2 or patients with the demyelinating form of Charcot-Marie-Tooth syndrome
* Known severe hypersensitivity to any study related agent excipient(s)
* Females only: pregnant or breastfeeding
* Any other condition that would, in the investigator's judgement, contraindicate the patient's participation in the clinical study
* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

City of Hope Medical Center

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Alex F Herrera

Role: PRINCIPAL_INVESTIGATOR

City of Hope Comprehensive Cancer Center

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

M D Anderson Cancer Center

Houston, Texas, United States

Site Status

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, Canada

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Canada

References

Explore related publications, articles, or registry entries linked to this study.

Herrera AF, Zain J, Savage KJ, Feldman T, Brammer JE, Chen L, Puverel S, Popplewell L, Budde LE, Mei M, Hosing C, Nair R, Leslie L, Daniels S, Peters L, Forman S, Rosen S, Kwak L, Iyer SP. Brentuximab vedotin plus cyclophosphamide, doxorubicin, etoposide, and prednisone followed by brentuximab vedotin consolidation in CD30-positive peripheral T-cell lymphomas: a multicentre, single-arm, phase 2 study. Lancet Haematol. 2024 Sep;11(9):e671-e681. doi: 10.1016/S2352-3026(24)00171-6. Epub 2024 Jul 24.

Reference Type DERIVED
PMID: 39067464 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

NCI-2017-00573

Identifier Type: REGISTRY

Identifier Source: secondary_id

17058

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

17058

Identifier Type: -

Identifier Source: org_study_id