A Study of Brentuximab Vedotin With Hodgkin Lymphoma (HL) and CD30-expressing Peripheral T-cell Lymphoma (PTCL)

Hodgkin Disease Clinical Trial

Official title:

A Phase 2 Open-label Study of Brentuximab Vedotin in Front-line Therapy of Hodgkin Lymphoma (HL) an dCD30-expressing Peripheral T-cell Lymphoma (PTCL) in Older Patients or Patients With Significant Comorbidities Ineligible for Standard Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01716806
• Other study ID #: SGN35-015
• Status: Completed
• Phase: Phase 2
• Start date: October 31, 2012
• Est. completion date: September 12, 2023

Study information

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

Clinical Trial Summary

This trial will study brentuximab vedotin to find out whether it is an effective treatment for Hodgkin lymphoma (HL) and peripheral T-cell lymphoma (PTCL). Participants in this study will be older or will have other conditions that make them unable to have standard chemotherapy treatment. The study will look at brentuximab vedotin alone and combined with other drugs.

Description:

This study is designed to evaluate the efficacy and tolerability of brentuximab vedotin as monotherapy and in combination with other agents as frontline therapy. There are 6 parts of the study. The population to be studied includes treatment-naïve patients with classical Hodgkin lymphoma (HL) or treatment-naïve patients with CD30-expressing peripheral T-cell lymphoma (PTCL).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 131
• Est. completion date: September 12, 2023
• Est. primary completion date: April 7, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Parts A, B, C, and D: 60 years of age or older

• Treatment-naive patients with histopathological diagnosis of classical Hodgkin lymphoma (Parts A, B, C, D, and E)

• Treatment-naive patients with CD30-expressing PTCL (Part F)

• Ineligible for or have declined initial conventional combination chemotherapy for HL (Parts A, B, C, and D)

• Unsuitable or unfit for initial conventional combination chemotherapy for HL (Part E) or CD30-expressing PTCL due to the presence of comorbidity-factors, as documented by:

• A CIRS score of 10 or greater

• Requiring assistance with or dependence on other for any instrumental activities of daily living (IADLs)

• Measurable disease of at least 1.5 cm as documented by radiographic technique

• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 3 (Parts, A, B, C, E, and F) or less than or equal to 2 (Part D)

Exclusion Criteria:

• Symptomatic neurologic disease compromising IADLs or requiring medication

• History of progressive multifocal leukoencephalopathy

• Grade 3 or higher viral, bacterial, or fungal infection within 2 weeks prior to the first dose of brentuximab vedotin

• Concurrent use of other investigational agents

• Chemotherapy, radiotherapy, biologics, and/or other treatment with immunotherapy not completed 4 weeks prior to first dose of study drug

• History of another malignancy within 1 year before first dose of study drug (Parts E and F only)

• Part D only:

• Received any prior immune-oncology therapy

• History of known or suspected autoimmune disease

• Prior allogeneic stem cell transplant

• History of cerebral vascular event within 6 months of first dose of study drug

• Active interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicology

• Known history of pancreatitis

• Parts D, E, and F only:

• Known cerebral/meningeal disease related to the underlying malignancy

• Systemic treatment with corticosteroids or other immunosuppressive medications within 1 week of enrollment

Related Conditions & MeSH terms

• Hodgkin Disease
• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• Peripheral T Cell Lymphoma

Intervention

Drug:
• brentuximab vedotin
1.8 mg/kg every 3 weeks by IV infusion
• bendamustine
70 mg/m^2 by IV infusion on Days 1 and 2 of 3-week cycle
• dacarbazine
375 mg/m^2 every 3 weeks by IV infusion
• nivolumab
3 mg/kg every 3 weeks by IV infusion

Locations

Country	Name	City	State
Canada	University of Alberta / Cross Cancer Institute	Edmonton	Alberta
Canada	London Health Sciences Centre - Victoria Hospital	London	Ontario
Canada	CIUSSS de L'Est de l'lle de Montreal / installation Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Royal Victoria Hospital, McGill University Health Centre	Montreal	Quebec
United States	New York Oncology Hematology, P.C.	Albany	New York
United States	Alaska Urological Institute	Anchorage	Alaska
United States	Arlington Cancer Center	Arlington	Texas
United States	Rocky Mountain Cancer Centers - Aurora	Aurora	Colorado
United States	Texas Oncology - Bedford	Bedford	Texas
United States	American Oncology Networks LLC	Bethesda	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Providence St Joseph Medical Center	Burbank	California
United States	Rush University Medical Center	Chicago	Illinois
United States	Oncology Hematology Care	Cincinnati	Ohio
United States	IACT Health	Columbus	Georgia
United States	James Cancer Hospital / Ohio State University	Columbus	Ohio
United States	Texas Oncology - Presbyterian Cancer Center Dallas	Dallas	Texas
United States	Texas Oncology - Denton South	Denton	Texas
United States	Karmanos Cancer Institute / Wayne State University	Detroit	Michigan
United States	City of Hope National Medical Center	Duarte	California
United States	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Texas Oncology - Fort Worth 12th Avenue	Fort Worth	Texas
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Prisma Health	Greenville	South Carolina
United States	Houston Methodist Cancer Center	Houston	Texas
United States	MD Anderson Cancer Center / University of Texas	Houston	Texas
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Texas Oncology - Longview	Longview	Texas
United States	Carbone Cancer Center / University of Wisconsin	Madison	Wisconsin
United States	Texas Oncology - McAllen	McAllen	Texas
United States	Minnesota Oncology Hematology P.A.	Minneapolis	Minnesota
United States	University of South Alabama - Mitchell Cancer Institute	Mobile	Alabama
United States	Morristown Medical Center/ Carol G. Simon Cancer Center	Morristown	New Jersey
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Columbia University Medical Center	New York	New York
United States	Illinois Cancer Specialists / Advocate Lutheran General Hospital	Niles	Illinois
United States	Nebraska Cancer Specialists	Omaha	Nebraska
United States	Wilshire Oncology Medical Group Inc.	Pomona	California
United States	Virginia Commonwealth University Medical Center	Richmond	Virginia
United States	James P. Wilmot Cancer Center / University of Rochester Medical Center	Rochester	New York
United States	Texas Oncology - Seton Williamson	Round Rock	Texas
United States	Oncology and Hematology Assoc of SW VA DBA Blue Ridge Cancer Care	Salem	Virginia
United States	Georgia Cancer Specialists / Northside Hospital Cancer Institute	Sandy Springs	Georgia
United States	Benaroya Research Institute/Virginia Mason Medical Center	Seattle	Washington
United States	Swedish Cancer Institute	Seattle	Washington
United States	Highlands Oncology Group	Springdale	Arkansas
United States	Northwest Cancer Specialists, P.C.	Tigard	Oregon
United States	Florida Cancer Affiliates	Trinity	Florida
United States	Arizona Cancer Center / University of Arizona	Tucson	Arizona
United States	Arizona Oncology Associates, PC - HOPE	Tucson	Arizona
United States	Wenatchee Valley Medical Center	Wenatchee	Washington
United States	Shenandoah Oncology P.C.	Winchester	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Seagen Inc.	Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) According to the Revised Response Criteria for Malignant Lymphoma (Parts A, B, and C)	Objective response rate (ORR) per investigator was defined as the percentage of subjects with complete response (CR) or partial response (PR) through the end of study or prior to the start of new anti-cancer treatment (including stem cell transplant, and excluding consolidative radiotherapy) other than the study treatment. For Parts A, B, and C the response was assessed using the Revised Response Criteria for Malignant Lymphoma (Cheson 2007).	Up to 81 months
Primary	ORR According to the Lugano Classification Revised Staging System for Nodal Non-Hodgkin and Hodgkin Lymphomas (Lugano Criteria) and the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) (Part D)	Objective response rate (ORR) per investigator was defined as the percentage of subjects with CR or PR through the end of study or prior to the start of new anti-cancer treatment (including stem cell transplant, and excluding consolidative radiotherapy) other than the study treatment. For Part D, the response was assessed using the Lugano Classification Revised Staging System for nodal non-Hodgkin and cHL (Lugano criteria) and the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC).	Up to 60 months
Primary	ORR According to Modified Lugano Criteria Per Blinded Independent Central Review (BICR) (Parts E and F)	Objective response rate (ORR) per investigator was defined as the percentage of subjects with CR or PR through the end of study or prior to the start of new anti-cancer treatment (including stem cell transplant, and excluding consolidative radiotherapy) other than the study treatment. For Parts E and F, the response was assessed per blinded independent central review (BICR) using the modified Lugano criteria.	Up to 31 months
Secondary	Number of Participants With Adverse Events	A treatment-emergent AE (TEAE) is defined as a newly occurring or worsening AE after the first dose of any study drug component. Treatment-related AEs are defined as treatment-emergent AEs that are determined by the investigator to be related to the treatment on study. TEAEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 4.03). The CTCAE displays Grades 1 through 5, where Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe or medically significant but not immediately life-threatening, Grade 4: Life-threatening consequences, Grade 5: Death related to AE.	Up to 122 months
Secondary	Number of Participants With Laboratory Abnormalities	Laboratory values were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 4.03). The CTCAE displays Grades 1 through 5, where Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe or medically significant but not immediately life-threatening, Grade 4: Life-threatening consequences, Grade 5: Death related to AE.	Up to 30 months
Secondary	Complete Response Rate	Complete response rate is defined as the percentage of patients with CR	Up to 81 months
Secondary	Duration of Complete Response	Duration of CR per investigator was defined as the time from start of the first documentation of CR to the first documentation of tumor progression or to death due to any cause, whichever came first. For Parts E and F, the assessment was per BICR.	Up to 81 months
Secondary	Duration of Objective Response	Duration of response per investigator was defined as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of tumor progression (PD) based on radiographic evidence of progression or to death due to any cause, whichever came first. For Parts E and F, the assessment was per BICR.	Up to 81 months
Secondary	Progression-free Survival	Progression-free survival (PFS) per investigator was defined as the time from start of study treatment to first documentation of tumor progression or to death due to any cause, whichever came first. For Parts E and F, the assessment was per BICR.	Up to 83 months
Secondary	Disease Control Rate	Disease control rate (DCR) per investigator was defined as the percentage of subjects with CR, PR, or SD, per investigator assessment of best clinical response per Cheson 2007. For Parts E and F, the assessment was per BICR.	Up to 81 months
Secondary	ORR According to Lugano Criteria Per BICR (Parts E and F)	Objective response rate (ORR) per investigator was defined as the percentage of subjects with CR or PR through the end of study or prior to the start of new anti-cancer treatment (including stem cell transplant, and excluding consolidative radiotherapy) other than the study treatment.	Up to 31 months
Secondary	B Symptom Resolution Rate	B symptom resolution rate per investigator was defined as the percentage of subjects with lymphoma-related B symptoms at baseline who achieved resolution of all B symptoms at any time during the treatment period.	Up to 42 weeks
Secondary	Number of Participants With Brentuximab Vedotin Antitherapeutic Antibodies (ATA)		Up to 30 months
Secondary	Number of Participants With Nivolumab Antitherapeutic Antibodies (ATA) (Part D Only)		Up to 30 months
Secondary	Overall Survival (Parts E and F Only)	Overall survival (OS) per investigator was defined as the time from date of enrollment to date of death due to any cause.	Up to 44 months