Hodgkin's Disease
Conditions
Brief summary
The purpose of this study is to determine whether an investigational immuno-therapy combination, nivolumab with Brentuximab vedotin compared to Brentuximab vedotin alone is safe and effective in the treatment of relapsed and refractory Classical Hodgkin Lymphoma. The participants of this trial will comprise of patients who have relapsed or did not respond to treatment and are not eligible for stem cell transplant
Interventions
BIOLOGICALNivolumab
Specified dose on specified days
BIOLOGICALBrentuximab vedotin
Specified dose on specified days
Sponsors
Seagen Inc.
Ono Pharmaceutical Co. Ltd
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. * Participants must have a pathologic diagnosis of classical Hodgkin lymphoma (cHL) who are relapsed or refractory with one of the following:. i) Autologous stem cell transplant (ASCT) ineligible patients. ii) Patients after failure of ASCT. \- Must have at least one lesion that is \> 15 mm (1.5 cm) in the longest diameter and avid by Fluoro Deoxy Glucose (FDG) Positron Emission Tomography (PET) scan.
Exclusion criteria
* Known central nervous system lymphoma. * Participants with nodular lymphocyte-predominant Hodgkin lymphoma (HL). * Participants with known history of pancreatitis or progressive multifocal leukoencephalopathy (PML). * Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | From randomization to date of death, or disease progression (up to approximately 45 months) | Progression Free Survival (PFS) is defined as time from date of randomization to death, or disease progression per investigator assessment estimated using the Kaplan-Meier (KM) product-limit method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate (CRR): | From randomization up to approximately 45 months | Complete Response Rate (CRR) is defined as the number of participants who have achieved complete response (Lugano 2014 classification) per investigator assessment. Complete response is considered a score of 1, 2, or 3. Per the Lugano criteria: Positron emission tomography (PET) negative scans are defined on the 5-point scale as scores of 1, 2, or 3 (where 1 = no uptake above background; 2 = uptake \</= mediastinum; and 3 = uptake \> mediastinum but \</= liver) and PET-positive scans, as scores of 4 or 5 (where 4 = uptake moderately higher than liver; 5 = uptake markedly higher than liver and/or new lesions). Response on PET scans should be reported as complete metabolic response (CMR) partial metabolic response (PMR), SMD (stable metabolic disease), or PMD (progressive metabolic disease). |
| Objective Response Rate (ORR) | From randomization up to approximately 45 months | Objective Response Rate (ORR) is defined as the number of participants with a Best Overall Response (BOR) of complete response (CR) or partial response (PR) (Lugano 2014 classification) per investigator assessment. Complete response is considered a score of 1, 2, or 3. Partial response is considered a score of 4 or 5. Per the Lugano criteria: Positron emission tomography (PET) negative scans are defined on the 5-point scale as scores of 1, 2, or 3 (where 1 = no uptake above background; 2 = uptake \</= mediastinum; and 3 = uptake \> mediastinum but \</= liver) and PET-positive scans, as scores of 4 or 5 (where 4 = uptake moderately higher than liver; 5 = uptake markedly higher than liver and/or new lesions). Response on PET scans should be reported as complete metabolic response (CMR) partial metabolic response (PMR), SMD (stable metabolic disease), or PMD (progressive metabolic disease). |
| Duration of Response (DOR) | From randomization to date of documented progression or death (up to approximately 45 months) | The time from first response (Complete response (CR) or partial response (PR)) to the date of initial objectively documented progression (2014 Lugano classification) or death due to any cause per investigator assessment estimated using the Kaplan-Meier (KM) product-limit method. Complete response is considered a score of 1, 2, or 3. Partial response is considered a score of 4 or 5. Per the Lugano criteria: Positron emission tomography (PET) negative scans are defined on the 5-point scale as scores of 1, 2, or 3 (where 1 = no uptake above background; 2 = uptake \</= mediastinum; and 3 = uptake \> mediastinum but \</= liver) and PET-positive scans, as scores of 4 or 5 (where 4 = uptake moderately higher than liver; 5 = uptake markedly higher than liver and/or new lesions). Response on PET scans should be reported as complete metabolic response (CMR) partial metabolic response (PMR), SMD (stable metabolic disease), or PMD (progressive metabolic disease). |
| Duration of Complete Response (DOCR) | From randomization to date of documented progression or death (up to approximately 45 months) | Duration of complete response (DOR) is defined as the time from first complete response to the date of initial objectively documented progression (2014 Lugano classification) or death due to any cause per investigator assessment estimated using the Kaplan-Meier (KM) product-limit method. Complete response is considered a score of 1, 2, or 3. Per the Lugano criteria: Positron emission tomography (PET) negative scans are defined on the 5-point scale as scores of 1, 2, or 3 (where 1 = no uptake above background; 2 = uptake \</= mediastinum; and 3 = uptake \> mediastinum but \</= liver) and PET-positive scans, as scores of 4 or 5 (where 4 = uptake moderately higher than liver; 5 = uptake markedly higher than liver and/or new lesions). Response on PET scans should be reported as complete metabolic response (CMR) partial metabolic response (PMR), SMD (stable metabolic disease), or PMD (progressive metabolic disease). |
| Overall Survival (OS) | From randomization to the date of death (up to approximately 3 years 7 months) | Overall Survival (OS) is defined as the time between the date of randomization and the date of death estimated using the Kaplan-Meier (KM) product-limit method |
Countries
Japan, Puerto Rico, United States
Participant flow
Pre-assignment details
23 participants were randomized for study participation, 22 received at least 1 dose of study drug.
Participants by arm
| Arm | Count |
|---|---|
| Nivolumab + Brentuximab Vedotin (BV) Nivolumab 360 mg IV every 3 weeks until progression or unacceptable toxicity (except for patients in CR who can discontinue at 2 years) plus BV 1.8 mg/kg IV every 3 weeks for up to 16 cycles, or until progression or unacceptable toxicity, whichever occurs first. | 12 |
| Brentuximab Vedotin (BV) BV alone 1.8 mg/kg every 3 weeks for up to 16 cycles, or until disease progression or unacceptable toxicity, whichever occurs first | 11 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Disease Progression | 2 | 6 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Other reasons | 2 | 0 |
| Overall Study | Participant discontinued study before treatment | 0 | 1 |
| Overall Study | Participant request to discontinue study treatment | 1 | 1 |
| Overall Study | Participants withdrew consent | 1 | 0 |
| Overall Study | Study drug toxicity | 2 | 2 |
Baseline characteristics
| Characteristic | Total | Nivolumab + Brentuximab Vedotin (BV) | Brentuximab Vedotin (BV) |
|---|---|---|---|
| Age, Continuous | 39.8 Years STANDARD_DEVIATION 14.5 | 37.5 Years STANDARD_DEVIATION 13.1 | 42.3 Years STANDARD_DEVIATION 16.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 9 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized ASIAN OTHER | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN | 5 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized JAPANESE | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized OTHER | 4 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized WHITE | 11 Participants | 7 Participants | 4 Participants |
| Sex: Female, Male Female | 8 Participants | 5 Participants | 3 Participants |
| Sex: Female, Male Male | 15 Participants | 7 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 12 | 0 / 10 |
| other Total, other adverse events | 12 / 12 | 10 / 10 |
| serious Total, serious adverse events | 6 / 12 | 1 / 10 |
Outcome results
Primary
Progression Free Survival (PFS)
Progression Free Survival (PFS) is defined as time from date of randomization to death, or disease progression per investigator assessment estimated using the Kaplan-Meier (KM) product-limit method.
Time frame: From randomization to date of death, or disease progression (up to approximately 45 months)
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab + Brentuximab Vedotin (BV) | Progression Free Survival (PFS) | 14.32 Months |
| Brentuximab Vedotin (BV) | Progression Free Survival (PFS) | 7.93 Months |
Secondary
Complete Response Rate (CRR):
Complete Response Rate (CRR) is defined as the number of participants who have achieved complete response (Lugano 2014 classification) per investigator assessment. Complete response is considered a score of 1, 2, or 3. Per the Lugano criteria: Positron emission tomography (PET) negative scans are defined on the 5-point scale as scores of 1, 2, or 3 (where 1 = no uptake above background; 2 = uptake \</= mediastinum; and 3 = uptake \> mediastinum but \</= liver) and PET-positive scans, as scores of 4 or 5 (where 4 = uptake moderately higher than liver; 5 = uptake markedly higher than liver and/or new lesions). Response on PET scans should be reported as complete metabolic response (CMR) partial metabolic response (PMR), SMD (stable metabolic disease), or PMD (progressive metabolic disease).
Time frame: From randomization up to approximately 45 months
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nivolumab + Brentuximab Vedotin (BV) | Complete Response Rate (CRR): | 4 Participants |
| Brentuximab Vedotin (BV) | Complete Response Rate (CRR): | 3 Participants |
Secondary
Duration of Complete Response (DOCR)
Duration of complete response (DOR) is defined as the time from first complete response to the date of initial objectively documented progression (2014 Lugano classification) or death due to any cause per investigator assessment estimated using the Kaplan-Meier (KM) product-limit method. Complete response is considered a score of 1, 2, or 3. Per the Lugano criteria: Positron emission tomography (PET) negative scans are defined on the 5-point scale as scores of 1, 2, or 3 (where 1 = no uptake above background; 2 = uptake \</= mediastinum; and 3 = uptake \> mediastinum but \</= liver) and PET-positive scans, as scores of 4 or 5 (where 4 = uptake moderately higher than liver; 5 = uptake markedly higher than liver and/or new lesions). Response on PET scans should be reported as complete metabolic response (CMR) partial metabolic response (PMR), SMD (stable metabolic disease), or PMD (progressive metabolic disease).
Time frame: From randomization to date of documented progression or death (up to approximately 45 months)
Population: All randomized participants with objective response of complete response (CR)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab + Brentuximab Vedotin (BV) | Duration of Complete Response (DOCR) | 7.85 Months |
| Brentuximab Vedotin (BV) | Duration of Complete Response (DOCR) | NA Months |
Secondary
Duration of Response (DOR)
The time from first response (Complete response (CR) or partial response (PR)) to the date of initial objectively documented progression (2014 Lugano classification) or death due to any cause per investigator assessment estimated using the Kaplan-Meier (KM) product-limit method. Complete response is considered a score of 1, 2, or 3. Partial response is considered a score of 4 or 5. Per the Lugano criteria: Positron emission tomography (PET) negative scans are defined on the 5-point scale as scores of 1, 2, or 3 (where 1 = no uptake above background; 2 = uptake \</= mediastinum; and 3 = uptake \> mediastinum but \</= liver) and PET-positive scans, as scores of 4 or 5 (where 4 = uptake moderately higher than liver; 5 = uptake markedly higher than liver and/or new lesions). Response on PET scans should be reported as complete metabolic response (CMR) partial metabolic response (PMR), SMD (stable metabolic disease), or PMD (progressive metabolic disease).
Time frame: From randomization to date of documented progression or death (up to approximately 45 months)
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab + Brentuximab Vedotin (BV) | Duration of Response (DOR) | 11.27 Months |
| Brentuximab Vedotin (BV) | Duration of Response (DOR) | 7.00 Months |
Secondary
Objective Response Rate (ORR)
Objective Response Rate (ORR) is defined as the number of participants with a Best Overall Response (BOR) of complete response (CR) or partial response (PR) (Lugano 2014 classification) per investigator assessment. Complete response is considered a score of 1, 2, or 3. Partial response is considered a score of 4 or 5. Per the Lugano criteria: Positron emission tomography (PET) negative scans are defined on the 5-point scale as scores of 1, 2, or 3 (where 1 = no uptake above background; 2 = uptake \</= mediastinum; and 3 = uptake \> mediastinum but \</= liver) and PET-positive scans, as scores of 4 or 5 (where 4 = uptake moderately higher than liver; 5 = uptake markedly higher than liver and/or new lesions). Response on PET scans should be reported as complete metabolic response (CMR) partial metabolic response (PMR), SMD (stable metabolic disease), or PMD (progressive metabolic disease).
Time frame: From randomization up to approximately 45 months
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nivolumab + Brentuximab Vedotin (BV) | Objective Response Rate (ORR) | 8 Participants |
| Brentuximab Vedotin (BV) | Objective Response Rate (ORR) | 5 Participants |
Secondary
Overall Survival (OS)
Overall Survival (OS) is defined as the time between the date of randomization and the date of death estimated using the Kaplan-Meier (KM) product-limit method
Time frame: From randomization to the date of death (up to approximately 3 years 7 months)
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab + Brentuximab Vedotin (BV) | Overall Survival (OS) | NA Months |
| Brentuximab Vedotin (BV) | Overall Survival (OS) | NA Months |