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

Phase 2

Completed

Conditions: Hodgkin Disease
Peripheral T Cell Lymphoma

Interventions: Drug: brentuximab vedotin
Drug: bendamustine
Drug: dacarbazine
Drug: nivolumab

Registration Number: NCT01716806

Lead Sponsor: Seagen Inc.

Brief 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.

Detailed 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 & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 131

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part C: Brentuximab Vedotin + Bendamustine in HL Patients	brentuximab vedotin	-
Part C: Brentuximab Vedotin + Bendamustine in HL Patients	bendamustine	-
Part D: Brentuximab Vedotin + Nivolumab in HL Patients	brentuximab vedotin	-
Part F: Brentuximab Vedotin in PTCL Patients	brentuximab vedotin	-
Part B: Brentuximab Vedotin + Dacarbazine in HL Patients	dacarbazine	-
Part B: Brentuximab Vedotin + Dacarbazine in HL Patients	brentuximab vedotin	-
Part A: Brentuximab Vedotin in HL Patients	brentuximab vedotin	-
Part D: Brentuximab Vedotin + Nivolumab in HL Patients	nivolumab	-
Part E: Brentuximab Vedotin in HL Patients	brentuximab vedotin	-

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) According to the Revised Response Criteria for Malignant Lymphoma (Parts A, B, and C)	Up to 81 months	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).
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)	Up to 60 months	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).
ORR According to Modified Lugano Criteria Per Blinded Independent Central Review (BICR) (Parts E and F)	Up to 31 months	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.

Secondary Outcome Measures

Name	Time	Method
Disease Control Rate	Up to 81 months	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.
ORR According to Lugano Criteria Per BICR (Parts E and F)	Up to 31 months	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.
Number of Participants With Adverse Events	Up to 122 months	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.
Number of Participants With Laboratory Abnormalities	Up to 30 months	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.
Complete Response Rate	Up to 81 months	Complete response rate is defined as the percentage of patients with CR
Duration of Complete Response	Up to 81 months	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.
Duration of Objective Response	Up to 81 months	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.
Progression-free Survival	Up to 83 months	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.
B Symptom Resolution Rate	Up to 42 weeks	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.
Number of Participants With Brentuximab Vedotin Antitherapeutic Antibodies (ATA)	Up to 30 months
Number of Participants With Nivolumab Antitherapeutic Antibodies (ATA) (Part D Only)	Up to 30 months
Overall Survival (Parts E and F Only)	Up to 44 months	Overall survival (OS) per investigator was defined as the time from date of enrollment to date of death due to any cause.

Trial Locations

Locations (54): University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
University of South Alabama - Mitchell Cancer Institute
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Mobile, Alabama, United States
Alaska Urological Institute
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Anchorage, Alaska, United States
Banner MD Anderson Cancer Center
🇺🇸
Gilbert, Arizona, United States
Arizona Oncology Associates, PC - HOPE
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Tucson, Arizona, United States
Arizona Cancer Center / University of Arizona
🇺🇸
Tucson, Arizona, United States
Highlands Oncology Group
🇺🇸
Springdale, Arkansas, United States
Providence St Joseph Medical Center
🇺🇸
Burbank, California, United States
City of Hope National Medical Center
🇺🇸
Duarte, California, United States
Wilshire Oncology Medical Group Inc.
🇺🇸
Pomona, California, United States
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University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States