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

Angioimmunoblastic T-Cell Lymphoma Clinical Trial

Official title:

A Phase 2 Study of Brentuximab Vedotin Plus Cyclophosphamide, Doxorubicin, Etoposide, and Prednisone (CHEP-BV) Followed by BV Consolidation in Patients With CD30-Positive Peripheral T-Cell Lymphomas

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03113500
• Other study ID #: 17058
• Secondary ID: NCI-2017-0057317
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 25, 2017
• Est. completion date: December 21, 2024

Study information

• Verified date: February 2024
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 48
• Est. completion date: December 21, 2024
• Est. primary completion date: July 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• 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
• Leukemia, T-Cell
• Leukemia-Lymphoma, Adult T-Cell
• Lymphoma
• Lymphoma, Large-Cell, Anaplastic
• Lymphoma, Non-Hodgkin
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma
• Peripheral T-Cell Lymphoma, Not Otherwise Specified

Intervention

Drug:
• Brentuximab Vedotin
Given IV
• Cyclophosphamide
Given IV
• Doxorubicin
Given IV
• Doxorubicin Hydrochloride
Given IV
• Etoposide
Given IV
• Etoposide Phosphate
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Prednisone
Given PO

Locations

Country	Name	City	State
Canada	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Response (CR) Rate After Cyclophosphamide, Doxorubicin, Etoposide, Prednisone, and Brentuximab Vedotin (CHEP-BV) Induction Therapy	CR rate was estimated by the proportion of evaluable patients achieving CR after CHEP-BV induction therapy, along with the 95% exact binomial confidence interval.	Up to the end of the CHEP-BV treatment
Secondary	Overall Survival at 1 Year	Overall survival (OS) was measured from enrollment to death from any cause. OS was estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error.	The time from enrollment to death from any cause assessed up to 1 year.