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

Study Overview
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Brief Summary
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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
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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).

Official Title
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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

Conditions
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Hodgkin Disease, Peripheral T Cell Lymphoma

Intervention / Treatment
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* Drug: brentuximab vedotin
* Drug: bendamustine
* Drug: dacarbazine
* Drug: nivolumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Brentuximab Vedotin in HL Patients<br> | Drug: brentuximab vedotin<br>* 1.8 mg/kg every 3 weeks by IV infusion<br>* Other names: Adcetris; SGN-35;|
| Experimental: Part B: Brentuximab Vedotin + Dacarbazine in HL Patients<br> | Drug: brentuximab vedotin<br>* 1.8 mg/kg every 3 weeks by IV infusion<br>* Other names: Adcetris; SGN-35;Drug: dacarbazine<br>* 375 mg/m^2 every 3 weeks by IV infusion<br>|
| Experimental: Part C: Brentuximab Vedotin + Bendamustine in HL Patients<br> | Drug: brentuximab vedotin<br>* 1.8 mg/kg every 3 weeks by IV infusion<br>* Other names: Adcetris; SGN-35;Drug: bendamustine<br>* 70 mg/m^2 by IV infusion on Days 1 and 2 of 3-week cycle<br>|
| Experimental: Part D: Brentuximab Vedotin + Nivolumab in HL Patients<br> | Drug: brentuximab vedotin<br>* 1.8 mg/kg every 3 weeks by IV infusion<br>* Other names: Adcetris; SGN-35;Drug: nivolumab<br>* 3 mg/kg every 3 weeks by IV infusion<br>|
| Experimental: Part E: Brentuximab Vedotin in HL Patients<br> | Drug: brentuximab vedotin<br>* 1.8 mg/kg every 3 weeks by IV infusion<br>* Other names: Adcetris; SGN-35;|
| Experimental: Part F: Brentuximab Vedotin in PTCL Patients<br> | Drug: brentuximab vedotin<br>* 1.8 mg/kg every 3 weeks by IV infusion<br>* Other names: Adcetris; SGN-35;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) according to the Revised Response Criteria for Malignant Lymphoma (Parts A, B, and C) | Defined as the proportion of patients with complete response (CR) or (PR) | Through 1 month following last dose; up to approximately 16 months | 
| 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) |  | Through 1 month following last dose; up to approximately 16 months | 
| ORR according to modified Lugano criteria per blinded independent central review (BICR) (Parts E and F) |  | Through 1 month following last dose; up to approximately 16 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events |  | Through 1 month following last dose of brentuximab vedotin (all parts) or through 100 days after last dose of nivolumab (Part D only); up to approximately 18 months | 
| Incidence of laboratory abnormalities |  | Through 1 month following last dose of brentuximab vedotin (all parts) or through 100 days after last dose of nivolumab (Part D only); up to approximately 18 months | 
| Complete remission (CR) rate | Defined as the proportion of patients with CR | Through 1 month following last dose; up to approximately 16 months | 
| Duration of complete response | Defined as the time from start of the first documentation of complete tumor response (CR) to the first documentation of tumor progression or death | Up to approximately 10 years | 
| Duration of objective response | Defined as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of tumor progression or death | Up to approximately 10 years | 
| Progression-free survival | Defined as the time from start of study treatment to first documentation of tumor progression or death due to any cause | Up to approximately 10 years | 
| Disease control rate | Defined as the proportion of patients with CR, PR, or stable disease (SD) | Up to approximately 10 years | 
| ORR according to Lugano criteria per BICR (Parts E and F) |  | Through 1 month following last dose; up to approximately 16 months | 
| B symptom resolution rate | Defined as the proportion of patients with lymphoma-related B symptoms at baseline who achieve resolution of all B symptoms at any time during the treatment period | Through 1 month following last dose; up to approximately 16 months | 
| Blood concentrations of brentuximab vedotin |  | Up to approximately 16 months. Cycle 1: predose, 30 minutes, and 24, 48, 168, and 336 hours post-dose; Cycles 2 and later (through 1 month post last dose): pre-dose and 30 minutes | 
| Incidence of brentuximab vedotin antitherapeutic antibodies (ATA) | Defined as the proportion of patients who develop ATA to brentuximab vedotin at any time during the study | Up to approximately 18 months. Cycles 1, 2, 4, and every 4 cycles thereafter (through 1 month post last dose [Parts A, B, and C] or through 100 days post last dose of nivolumab [Part D only]): predose | 
| Blood concentrations of nivolumab (Part D only) |  | Up to approximately 16 months. Cycle 1: predose, 30 minutes, and 168 and 336 hours post-dose; Cycles 2, 4, and every 4 cycles thereafter (through 1 month post last dose): pre-dose and 30 minutes | 
| Incidence of nivolumab antitherapeutic antibodies (ATA) (Part D only) | Defined as the proportion of patients who develop ATA to nivolumab at any time during the study | Up to approximately 18 months. Cycles 1, 2, 4, and every 4 cycles thereafter (through 100 days post last dose of nivolumab): predose | 
| Overall survival (Parts E and F only) | Defined as the time from start of study treatment to date of death due to any cause | Up to approximately 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antibody-Drug Conjugate, Antibodies, Monoclonal, Hematologic Diseases, Hodgkin Disease, Antigens, CD30, Lymphoma, monomethylauristatin E, Drug Therapy, CD30-expression, PTCL, Seattle Genetics