Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma

Hodgkin Lymphoma Clinical Trial

Official title:

Multiple Part Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma Subjects

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03646123
• Other study ID #: SGN35-027
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 28, 2019
• Est. completion date: June 7, 2026

Study information

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

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 255
• Est. completion date: June 7, 2026
• Est. primary completion date: November 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hodgkin Disease
• Hodgkin Lymphoma
• Lymphoma

Intervention

Drug:
• brentuximab vedotin
1.2 mg/kg by IV infusion
• doxorubicin
25 mg/m^2 by IV infusion
• vinblastine
6 mg/m^2 by IV infusion
• dacarbazine
375 mg/m^2 by IV infusion
• G-CSF
Granulocyte colony stimulating factor (G-CSF) primary prophylaxis administered 24-36 hours after each dose of A+AVD
• nivolumab
240 mg by IV infusion

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	Other
Australia	Ballarat Regional Integrated Cancer Care	Ballarat	Other
Australia	Monash Medical Centre	Clayton	Other
Australia	Epworth Healthcare	Victoria	Other
Czechia	Fakultni nemocnice Hradec Kralove-oddeleni klinicke hematologie	Hradec Kralove	Other
Czechia	Fakultni Nemocnice Kralovske Vinohrady	Praha 10	Other
Italy	Azienda Ospedaliera Spedali Civili di Brescia	Brescia	Other
Italy	IRCSS Policlinico San Matteo	Pavia	Other
Italy	Azienda Ospedaliera Universitaria Senese	Siena	Other
Italy	Azienda Ospedaliera Citta della Salute e della Scienza di Torino	Torino	Other
Poland	Pratia MCM Krakow	Krakow	Other
Spain	Hospital del Mar	Barcelona	Other
Spain	Hospital Universitari Vall d'Hebron	Barcelona	Other
Spain	Institut Catala d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)	Barcelona	Other
Spain	Hospital Universitario de Girona Doctor Josep Trueta	Girona	Other
Spain	Hospital Universitario 12 de Octubre	Madrid	Other
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid	Other
Spain	Hospital Puerta de Hierro Majadahonda	Majadahonda	Other
Spain	Hospital Universitario Central de Asturias	Oviedo	Other
Spain	Hospital Clinico Universitario de Salamanca	Salamanca	Other
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia	Other
United States	New York Oncology Hematology, P.C.	Albany	New York
United States	Rocky Mountain Cancer Centers - Aurora	Aurora	Colorado
United States	Texas Oncology - Austin Midtown	Austin	Texas
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	New Jersey Hematology Oncology Associates, LLC	Brick	New Jersey
United States	Medical University of South Carolina/Hollings Cancer Center	Charleston	South Carolina
United States	Oncology Hematology Care	Cincinnati	Ohio
United States	Cleveland Clinic, The	Cleveland	Ohio
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	University of Colorado Health Memorial Hospital	Colorado Springs	Colorado
United States	Texas Oncology - Medical City Dallas	Dallas	Texas
United States	Cancer Centers of Colorado - Denver	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	Karmanos Cancer Institute / Wayne State University	Detroit	Michigan
United States	Minnesota Oncology Hematology P.A.	Edina	Minnesota
United States	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Texas Oncology - Flower Mound	Flower Mound	Texas
United States	Poudre Valley Health System (PVHS)	Fort Collins	Colorado
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Texas Oncology - Fort Worth 12th Avenue	Fort Worth	Texas
United States	Los Angeles Cancer Network / Compassionate Care Research Group	Fountain Valley	California
United States	Regional Cancer Care Associates - Freehold	Freehold	New Jersey
United States	SCL Health - St. Mary's Hospital & Medical Center	Grand Junction	Colorado
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	MD Anderson Cancer Center / University of Texas	Houston	Texas
United States	Regional Cancer Care Associates - Howell	Howell	New Jersey
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	University of Tennessee	Knoxville	Tennessee
United States	Cardinal Bernardin Cancer Center / Loyola University Medical Center	Maywood	Illinois
United States	Miami Cancer Institute at Baptist Health, Inc.	Miami	Florida
United States	Morristown Medical Center/ Carol G. Simon Cancer Center	Morristown	New Jersey
United States	Regional Cancer Care Associates - Mount Holly	Mount Holly	New Jersey
United States	CareMount Medical Group	Mount Kisco	New York
United States	Tennessee Oncology-Nashville/Sarah Cannon Research Institute	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	Illinois Cancer Specialists	Niles	Illinois
United States	Vista Oncology Inc PS	Olympia	Washington
United States	Illinois Cancer Care	Peoria	Illinois
United States	Providence Portland Medical Center	Portland	Oregon
United States	Clinical Research Alliance - Abraham Mittelman, MD, LLC	Purchase	New York
United States	Washington University in St Louis	Saint Louis	Missouri
United States	Florida Cancer Specialists - North Region	Saint Petersburg	Florida
United States	Oncology and Hematology Assoc of SW VA DBA Blue Ridge Cancer Care	Salem	Virginia
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Texas Oncology - San Antonio Medical Center	San Antonio	Texas
United States	Seattle Cancer Care Alliance / University of Washington	Seattle	Washington
United States	Regional Cancer Care Associates - Central Jersey	Somerville	New Jersey
United States	Regional Cancer Care Associates - Sparta	Sparta	New Jersey
United States	Toledo Clinic Cancer Center	Toledo	Ohio
United States	Texas Oncology - Northeast Texas	Tyler	Texas
United States	Clinical Research Alliance - Morton Coleman, MD	Westbury	New York
United States	Wake Forest Baptist Medical Center / Wake Forest University	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Seagen Inc.	Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Australia,  Czechia,  Italy,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Febrile Neutropenia (FN) Rate (Part A)	The FN rate is defined as the number of participants who experience treatment-emergent FN.	7.5 months
Primary	Complete Response (CR) Rate (Parts B and C)	CR rate at EOT is defined as the percentage of subjects with CR at EOT, according to the Lugano Classification Revised Staging System for malignant lymphoma (Cheson 2014) with the incorporation of LYRIC (Cheson 2016), in subjects with previously untreated cHL.	7.8 months
Secondary	Primary Refractory Disease Rate (Part A)	The primary refractory disease rate is defined as the percentage of participants with less than complete response or relapse within 3 months of EOT, according to the Lugano Classification Revised Staging System for nodal non-Hodgkin and Hodgkin lymphomas	10.2 months
Secondary	Complete Response Rate (Part A)	The complete response rate is defined as the percentage of participants with CR at EOT according to the Lugano Classification Revised Staging System for nodal non-Hodgkin and Hodgkin lymphomas (Cheson 2014).	7.2 months
Secondary	Physician-reported Progression Free Survival (PFS) (Part A)	The physician-reported PFS rate at 2 years is estimated based on Kaplan-Meier methodology.	24 months
Secondary	Subsequent Anticancer Therapy Utilization Rate (Part A)	Number of participants with subsequent anticancer therapy	33.8 months
Secondary	Actual Dose Intensity: Brentuximab Vedotin (Part A)		6.5 months
Secondary	Actual Dose Intensity: Doxorubicin, Vinblastine, Dacarbazine (Part A)		6.5 months
Secondary	Relative Dose Intensity (Part A)		6.5 months
Secondary	Rate of Dose Reduction and Delays: Brentuximab Vedotin (Part A)		6.5 months
Secondary	Rate of Dose Reduction and Delays: Doxorubicin (Part A)		6.5 months
Secondary	Rate of Dose Reduction and Delays: Vinblastine (Part A)		6.5 months
Secondary	Rate of Dose Reduction and Delays: Dacarbazine (Part A)		6.5 months
Secondary	Incidence of Adverse Events (Parts B and C)		8.9 months
Secondary	Incidence of Laboratory Abnormalities (Parts B and C)	Laboratory values were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 4.03).	8.9 months
Secondary	Overall Response Rate (ORR) at EOT (Parts B and C)	ORR is defined as the proportion of participants with CR or partial response (PR) at EOT according to the Lugano Classification Revised Staging System for malignant lymphoma (Cheson 2014) with the incorporation of LYRIC (Cheson 2016) in subjects with previously untreated cHL.	7.8 months