Clinical trial NCT03646123: Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma
Official title: Multiple Part Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hodgkin Lymphoma
Keywords: Brentuximab vedotin
Doxorubicin
Vinblastine
Dacarbazine
Nivolumab
Seattle Genetics
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2018-08-24
Enrollment: 255
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial will study two treatment combinations for classical Hodgkin lymphoma (cHL). This trial will find out if these two treatment combinations work to treat cHL. It will also find out what side effects occur. A side effect is anything the drug does besides treating cancer. This study will have three parts (Parts A, B, and C).

The drugs used in Part A are a combination of targeted anticancer drug (brentuximab vedotin) and three chemotherapy drugs (doxorubicin, vinblastine, and dacarbazine). These four drugs are called "A+AVD." Participants will be treated with granulocyte colony stimulating factor (G-CSF) following every dose of A+AVD for 6 cycles of treatment (12 doses).

Part A will look at whether the A+AVD drug combination reduces the number of participants who experience the side effect of febrile neutropenia. Febrile neutropenia is a very low white blood cell count and a fever, which can be life threatening.

Parts B and C will use drug combination of brentuximab vedotin, plus nivolumab, doxorubicin, and dacarbazine. These four drugs are called "AN+AD." Parts B and C will study how well the drugs work to treat cHL and what side effects they cause.

Detailed description: This study will have three parts.

Part A of the study is designed to evaluate the incidence of febrile neutropenia, efficacy, and dose intensity in participants with advanced stage classical Hodgkin lymphoma (cHL) receiving granulocyte colony stimulating factor primary prophylaxis (G-PP) administration during treatment with frontline A+AVD. In Part A, participants will be treated with granulocyte colony stimulating factor (G-CSF) following every dose of A+AVD for 6 cycles of treatment. Participants will be treated using institutional standard of care practices for the majority of treatment decisions.

Part B is designed to evaluate the combination of brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine (AN+AD) as frontline treatment in participants with advanced cHL. In Part B, participants will be given AN+AD combination for 6 cycles of treatment. This part of the trial will look at whether this combination of drugs is effective and tolerable in participants with Stage II with bulky mediastinal disease and Stage III or IV cHL.

Part C is designed to evaluate AN+AD as frontline treatment in participants with early stage cHL. In Part C, participants will be given AN+AD combination for 4 cycles of treatment. This part of the trial will look at whether this combination of drugs is effective and tolerable in participants with Stage I or II cHL with non-bulky mediastinal disease.

Eligibility criteria: Inclusion Criteria

* Treatment-naïve, classic Hodgkin lymphoma (cHL) participants

  * Participants enrolling in Part A of the study must have Ann Arbor Stage III or IV disease
  * Participants enrolling in Part B of the study must have Ann Arbor Stage I or II cH: with bulky mediastinal disease, or Stage III or IV
  * Participants enrolling in Part C of the study must have Ann Arbor Stage I or II cHL without bulky disease
* Histologically confirmed cHL according to the current World Health Organization (WHO) Classification
* Bidimensional measurable disease as documented by PET/CT or CT imaging
* Age 12 years or older in the United States. For regions outside of the US, participants must 18 years or older.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

Exclusion Criteria

* Nodular lymphocyte predominant HL
* History of another malignancy within 3 years of the first dose of study drug or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk or metastasis or death. Participants with nonmelanoma skin cancer, localized prostate cancer, or carcinoma in situ of any type are not excluded if they have undergone complete resection
* Prior immunosuppressive chemotherapy, therapeutic radiation, or any immunotherapy within 4 weeks of the first study drug dose
* Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
* Active cerebral/meningeal disease related to the underlying malignancy
* Any active Grade 3 or higher viral, bacterial, or fungal infection within two weeks of the first dose of study drug (Grade 3 defined by the National Cancer Institute's Common Terminology Criteria for Adverse Events, NCI CTCAE Version 4.03)
* Current therapy with other systemic anti-neoplastic or investigational agents
* Planned consolidative radiotherapy (Parts B and C only)
* Active interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity (Parts B and C only)
* Grade 3 or higher pulmonary disease unrelated to underlying malignancy
* Documented history of idiopathic interstitial pneumonia or diffusing capacity of the lung for carbon monoxide \<50% predicted
* History of a cerebral vascular event within 6 months of first dose of study drug
* Child-Pugh B or C hepatic impairment
* Grade 2 or higher peripheral sensory or motor neuropathy
* Participants with acute or chronic graft-versus-host-disease (GvHD) or receiving immunosuppressive therapy as treatment or as prophylaxis against GvHD
* Previous treatment with brentuximab vedotin
* Participants who are pregnant or breastfeeding
* Other serious condition that would impair the participant's ability to receive or tolerate the planned treatment and follow-up

Primary outcomes:
measure: Febrile Neutropenia (FN) Rate (Part A)
timeFrame: 7.5 months
measure: Complete Response (CR) Rate (Parts B and C)
timeFrame: 7.8 months
Secondary outcomes:
measure: Primary Refractory Disease Rate (Part A)
timeFrame: 10.2 months
measure: Complete Response Rate (Part A)
timeFrame: 7.2 months
measure: Physician-reported Progression Free Survival (PFS) (Part A)
timeFrame: 24 months
measure: Subsequent Anticancer Therapy Utilization Rate (Part A)
timeFrame: 33.8 months
measure: Actual Dose Intensity: Brentuximab Vedotin (Part A)
timeFrame: 6.5 months
measure: Actual Dose Intensity: Doxorubicin, Vinblastine, Dacarbazine (Part A)
timeFrame: 6.5 months
measure: Relative Dose Intensity (Part A)
timeFrame: 6.5 months
measure: Rate of Dose Reduction and Delays: Brentuximab Vedotin (Part A)
timeFrame: 6.5 months
measure: Rate of Dose Reduction and Delays: Doxorubicin (Part A)
timeFrame: 6.5 months
measure: Rate of Dose Reduction and Delays: Vinblastine (Part A)
timeFrame: 6.5 months
measure: Rate of Dose Reduction and Delays: Dacarbazine (Part A)
timeFrame: 6.5 months
measure: Incidence of Adverse Events (Parts B and C)
timeFrame: 8.9 months
measure: Incidence of Laboratory Abnormalities (Parts B and C)
timeFrame: 8.9 months
measure: Overall Response Rate (ORR) at EOT (Parts B and C)
timeFrame: 7.8 months
Other outcomes:
Locations:
city: Fountain Valley
country: United States
facility: Los Angeles Cancer Network / Compassionate Care Research Group
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers - Aurora
state: Colorado
city: Colorado Springs
country: United States
facility: University of Colorado Health Memorial Hospital
state: Colorado
city: Denver
country: United States
facility: Cancer Centers of Colorado - Denver
state: Colorado
city: Fort Collins
country: United States
facility: Poudre Valley Health System (PVHS)
state: Colorado
city: Grand Junction
country: United States
facility: SCL Health - St. Mary's Hospital & Medical Center
state: Colorado
city: Miami
country: United States
facility: Miami Cancer Institute at Baptist Health, Inc.
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists - North Region
state: Florida
city: Maywood
country: United States
facility: Cardinal Bernardin Cancer Center / Loyola University Medical Center
state: Illinois
city: Niles
country: United States
facility: Illinois Cancer Specialists
state: Illinois
city: Peoria
country: United States
facility: Illinois Cancer Care
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute / Wayne State University
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Edina
country: United States
facility: Minnesota Oncology Hematology P.A.
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University in St Louis
state: Missouri
city: Brick
country: United States
facility: New Jersey Hematology Oncology Associates, LLC
state: New Jersey
city: Freehold
country: United States
facility: Regional Cancer Care Associates - Freehold
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Howell
country: United States
facility: Regional Cancer Care Associates - Howell
state: New Jersey
city: Morristown
country: United States
facility: Morristown Medical Center/ Carol G. Simon Cancer Center
state: New Jersey
city: Mount Holly
country: United States
facility: Regional Cancer Care Associates - Mount Holly
state: New Jersey
city: Somerville
country: United States
facility: Regional Cancer Care Associates - Central Jersey
state: New Jersey
city: Sparta
country: United States
facility: Regional Cancer Care Associates - Sparta
state: New Jersey
city: Albany
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: Mount Kisco
country: United States
facility: CareMount Medical Group
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Purchase
country: United States
facility: Clinical Research Alliance - Abraham Mittelman, MD, LLC
state: New York
city: Westbury
country: United States
facility: Clinical Research Alliance - Morton Coleman, MD
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center / Wake Forest University
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic, The
state: Ohio
city: Toledo
country: United States
facility: Toledo Clinic Cancer Center
state: Ohio
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center
state: Oregon
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Charleston
country: United States
facility: Medical University of South Carolina/Hollings Cancer Center
state: South Carolina
city: Knoxville
country: United States
facility: University of Tennessee
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology-Nashville/Sarah Cannon Research Institute
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology - Austin Midtown
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Medical City Dallas
state: Texas
city: Flower Mound
country: United States
facility: Texas Oncology - Flower Mound
state: Texas
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology - Fort Worth 12th Avenue
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center / University of Texas
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology - San Antonio Medical Center
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Northeast Texas
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Salem
country: United States
facility: Oncology and Hematology Assoc of SW VA DBA Blue Ridge Cancer Care
state: Virginia
city: Kennewick
country: United States
facility: Kadlec Clinic Hematology and Oncology
state: Washington
city: Olympia
country: United States
facility: Vista Oncology Inc PS
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance / University of Washington
state: Washington
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: Other
city: Ballarat
country: Australia
facility: Ballarat Regional Integrated Cancer Care
state: Other
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Other
city: Victoria
country: Australia
facility: Epworth Healthcare
state: Other
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove-oddeleni klinicke hematologie
state: Other
city: Praha 10
country: Czechia
facility: Fakultni Nemocnice Kralovske Vinohrady
state: Other
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia
state: Other
city: Pavia
country: Italy
facility: IRCSS Policlinico San Matteo
state: Other
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese
state: Other
city: Torino
country: Italy
facility: Azienda Ospedaliera Citta della Salute e della Scienza di Torino
state: Other
city: Krakow
country: Poland
facility: Pratia MCM Krakow
state: Other
city: Barcelona
country: Spain
facility: Hospital del Mar
state: Other
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Other
city: Barcelona
country: Spain
facility: Institut Catala d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
state: Other
city: Girona
country: Spain
facility: Hospital Universitario de Girona Doctor Josep Trueta
state: Other
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
state: Other
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
state: Other
city: Majadahonda
country: Spain
facility: Hospital Puerta de Hierro Majadahonda
state: Other
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Other
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
state: Other
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
state: Other
Study officials:
affiliation: Seagen Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References: