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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03646123




Registration number
NCT03646123
Ethics application status
Date submitted
22/08/2018
Date registered
24/08/2018
Date last updated
5/11/2024

Titles & IDs
Public title
Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma
Scientific title
Multiple Part Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma Subjects
Secondary ID [1] 0 0
SGN35-027
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hodgkin Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Hodgkin's

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - brentuximab vedotin
Treatment: Drugs - doxorubicin
Treatment: Drugs - vinblastine
Treatment: Drugs - dacarbazine
Treatment: Drugs - G-CSF
Treatment: Drugs - nivolumab

Experimental: Part A: A+AVD - Brentuximab vedotin (A) plus doxorubicin (+A), vinblastine (V), and dacarbazine (D) administered by intravenous (IV) infusion in participants with advanced stage classical Hodgkin lymphoma (cHL) during each treatment cycle.

Experimental: Part B: AN+AD - Brentuximab vedotin (A) plus nivolumab (N), doxorubicin (+A), and dacarbazine (D) administered separately by IV infusion in participants with Stage II bulky mediastinal disease and Stage III or IV cHL during each treatment cycle.

Experimental: Part C: AN+AD - Brentuximab vedotin (A) plus nivolumab (N), doxorubicin (+A), and dacarbazine (D) administered separately by IV infusion in participants with Stage I or II cHL with non-bulky mediastinal disease during each treatment cycle.


Treatment: Drugs: brentuximab vedotin
1.2 mg/kg by IV infusion

Treatment: Drugs: doxorubicin
25 mg/m\^2 by IV infusion

Treatment: Drugs: vinblastine
6 mg/m\^2 by IV infusion

Treatment: Drugs: dacarbazine
375 mg/m\^2 by IV infusion

Treatment: Drugs: G-CSF
Granulocyte colony stimulating factor (G-CSF) primary prophylaxis administered 24-36 hours after each dose of A+AVD

Treatment: Drugs: nivolumab
240 mg by IV infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Febrile Neutropenia (FN) Rate (Part A)
Timepoint [1] 0 0
7.5 months
Primary outcome [2] 0 0
Complete Response (CR) Rate (Parts B and C)
Timepoint [2] 0 0
7.8 months
Secondary outcome [1] 0 0
Primary Refractory Disease Rate (Part A)
Timepoint [1] 0 0
10.2 months
Secondary outcome [2] 0 0
Complete Response Rate (Part A)
Timepoint [2] 0 0
7.2 months
Secondary outcome [3] 0 0
Physician-reported Progression Free Survival (PFS) (Part A)
Timepoint [3] 0 0
24 months
Secondary outcome [4] 0 0
Subsequent Anticancer Therapy Utilization Rate (Part A)
Timepoint [4] 0 0
33.8 months
Secondary outcome [5] 0 0
Actual Dose Intensity: Brentuximab Vedotin (Part A)
Timepoint [5] 0 0
6.5 months
Secondary outcome [6] 0 0
Actual Dose Intensity: Doxorubicin, Vinblastine, Dacarbazine (Part A)
Timepoint [6] 0 0
6.5 months
Secondary outcome [7] 0 0
Relative Dose Intensity (Part A)
Timepoint [7] 0 0
6.5 months
Secondary outcome [8] 0 0
Rate of Dose Reduction and Delays: Brentuximab Vedotin (Part A)
Timepoint [8] 0 0
6.5 months
Secondary outcome [9] 0 0
Rate of Dose Reduction and Delays: Doxorubicin (Part A)
Timepoint [9] 0 0
6.5 months
Secondary outcome [10] 0 0
Rate of Dose Reduction and Delays: Vinblastine (Part A)
Timepoint [10] 0 0
6.5 months
Secondary outcome [11] 0 0
Rate of Dose Reduction and Delays: Dacarbazine (Part A)
Timepoint [11] 0 0
6.5 months
Secondary outcome [12] 0 0
Incidence of Adverse Events (Parts B and C)
Timepoint [12] 0 0
8.9 months
Secondary outcome [13] 0 0
Incidence of Laboratory Abnormalities (Parts B and C)
Timepoint [13] 0 0
8.9 months
Secondary outcome [14] 0 0
Overall Response Rate (ORR) at EOT (Parts B and C)
Timepoint [14] 0 0
7.8 months

Eligibility
Key inclusion 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
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/01/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
23/08/2024
Sample size
Target
Accrual to date
Final
255
Recruitment in Australia
Recruitment state(s)
Othe
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Ballarat Regional Integrated Cancer Care - Ballarat
Recruitment hospital [3] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [4] 0 0
Epworth Healthcare - Victoria
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3350 - Ballarat
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3002 - Victoria
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
Oregon
Country [14] 0 0
United States of America
State/province [14] 0 0
South Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Tennessee
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
United States of America
State/province [17] 0 0
Utah
Country [18] 0 0
United States of America
State/province [18] 0 0
Virginia
Country [19] 0 0
United States of America
State/province [19] 0 0
Washington
Country [20] 0 0
Czechia
State/province [20] 0 0
Other
Country [21] 0 0
Italy
State/province [21] 0 0
Other
Country [22] 0 0
Poland
State/province [22] 0 0
Other
Country [23] 0 0
Spain
State/province [23] 0 0
Other

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Seagen Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Bristol-Myers Squibb
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT03646123
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Monitor
Address 0 0
Seagen Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03646123