Hodgkin Disease
Conditions
Keywords
Antibody-Drug Conjugate, Antibodies, Monoclonal, Hodgkin Disease, Hematologic Diseases, Drug Therapy, Immunotherapy, Antigens, CD30, Lymphoma, monomethylauristatin E
Brief summary
The purpose of this study is to assess safety and efficacy of brentuximab vedotin in combination with bendamustine in patients with relapsed or refractory Hodgkin lymphoma. It is an open-label, 2-stage study designed to determine the recommended dose level of bendamustine in combination with brentuximab vedotin. The study will assess the safety profile of the combination treatment and determine what proportion of patients achieve a complete remission.
Interventions
DRUGbrentuximab vedotin
1.8 mg/kg every 3 weeks by intravenous (IV) infusion
DRUGbendamustine
90 mg/m2 on Days 1 and 2 of 3-week cycles
Sponsors
Seagen Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histopathological diagnosis of classical Hodgkin lymphoma * Failed standard front-line therapy * Measurable disease of at least 1.5 cm as documented by radiographic technique * Eastern Cooperative Oncology Group performance status less than or equal to 2
Exclusion criteria
* Received prior salvage therapy, including radiotherapy * Chemotherapy, radiotherapy, biologics, and/or other treatment with immunotherapy not completed 4 weeks prior to first dose of study drug * Concurrent use of other investigational agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Remission Rate | Up to 4.6 months | Complete remission rate among all subjects (Phase 1 and 2 combined) treated at the dose level selected for Phase 2. Complete remission (CR) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma is a disappearance of all evidence of disease. |
| Incidence of Adverse Events (AEs) | Up to 13.8 months | All AEs reported after initiation of treatment and pre-existing conditions that worsen after initiation of treatment will be considered treatment-emergent AEs (TEAEs). All AEs will be coded by system organ class, MedDRA preferred term, and severity grade using NCI CTCAE V4.03. All recorded AEs will be included in the data listings. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose-limiting Toxicities | Up to 3 weeks; first cycle of therapy through the first day of Cycle 2 | Incidence of dose-limiting toxicity (DLT) was evaluated in an initial safety cohort of 10 patients who were followed for protocol-defined DLT events until Cycle 2 Day 1. |
| Overall Best Response Rate | Up to 4.6 months | Percentage of participants who achieved a best response of complete remission (CR, disappearance of all evidence of disease), partial remission (PR, regression of greater than or equal to 50% of measurable disease and no new sites), stable disease (SD, failure to obtain a complete or partial response or progressive disease), or progressive disease (PD, any new lesion or increase by 50% or more of previously involved sites from nadir) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma |
| Duration of Response | Up to 47.8 months | The time from first observation of remission to disease progression/relapse or death from any cause, whichever occurs first. |
| Progression-free Survival | Up to 49 months | The time from first dose of study medication to first documentation of disease progression/relapse, or to death due to any cause, whichever occurs first. |
Countries
United States
Participant flow
Recruitment details
June 2013 - July 2016
Participants by arm
| Arm | Count |
|---|---|
| Brentuximab Vedotin + Bendamustine brentuximab vedotin: 1.8 mg/kg on Day 1 of 3-week cycles by intravenous (IV) infusion
bendamustine: 90 mg/m\^2 on Days 1 and 2 of 3-week cycles by intravenous (IV) infusion | 55 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 5 |
| Overall Study | Lost to Follow-up | 5 |
| Overall Study | Study Termination by Sponsor | 42 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Brentuximab Vedotin + Bendamustine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 50 Participants |
| Age, Continuous | 36 years |
| Eastern Cooperative Group Oncology Performance Status 0 | 31 Participants |
| Eastern Cooperative Group Oncology Performance Status 1 | 23 Participants |
| Eastern Cooperative Group Oncology Performance Status 2 | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 51 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 46 Participants |
| Region of Enrollment United States | 55 participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 55 |
| other Total, other adverse events | 55 / 55 |
| serious Total, serious adverse events | 18 / 55 |
Outcome results
Primary
Complete Remission Rate
Complete remission rate among all subjects (Phase 1 and 2 combined) treated at the dose level selected for Phase 2. Complete remission (CR) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma is a disappearance of all evidence of disease.
Time frame: Up to 4.6 months
Population: All patients who received at least 2 cycles of combination treatment at the recommended dose level and had a baseline tumor assessment and at least 1 postbaseline tumor assessment, or who had documented disease progression (including clinical disease progression) at any time after the first dose of combination therapy at the recommended dose level.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brentuximab Vedotin + Bendamustine | Complete Remission Rate | 73.6 percentage of participants |
Primary
Incidence of Adverse Events (AEs)
All AEs reported after initiation of treatment and pre-existing conditions that worsen after initiation of treatment will be considered treatment-emergent AEs (TEAEs). All AEs will be coded by system organ class, MedDRA preferred term, and severity grade using NCI CTCAE V4.03. All recorded AEs will be included in the data listings.
Time frame: Up to 13.8 months
Population: All subjects who were enrolled and received at least 1 dose of brentuximab vedotin.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brentuximab Vedotin + Bendamustine | Incidence of Adverse Events (AEs) | Any Treatment-Emergent Adverse Event (TEAE) | 55 Participants |
| Brentuximab Vedotin + Bendamustine | Incidence of Adverse Events (AEs) | Any TEAE with Severity >= Grade 3 | 31 Participants |
| Brentuximab Vedotin + Bendamustine | Incidence of Adverse Events (AEs) | Any Treatment-Related Adverse Event | 54 Participants |
| Brentuximab Vedotin + Bendamustine | Incidence of Adverse Events (AEs) | Any Serious Adverse Event | 18 Participants |
| Brentuximab Vedotin + Bendamustine | Incidence of Adverse Events (AEs) | Any Treatment-Related Serious Adverse Event | 15 Participants |
| Brentuximab Vedotin + Bendamustine | Incidence of Adverse Events (AEs) | Treatment Discontinuation Due to Adverse Event | 20 Participants |
Secondary
Duration of Response
The time from first observation of remission to disease progression/relapse or death from any cause, whichever occurs first.
Time frame: Up to 47.8 months
Population: Patients with a complete or partial response who received at least 2 cycles of combination treatment and had a baseline tumor assessment and at least 2 post-baseline tumor assessment, or who had documented disease progression (including clinical disease progression) at any time after the first dose of combination therapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brentuximab Vedotin + Bendamustine | Duration of Response | 43.0 months |
Secondary
Incidence of Dose-limiting Toxicities
Incidence of dose-limiting toxicity (DLT) was evaluated in an initial safety cohort of 10 patients who were followed for protocol-defined DLT events until Cycle 2 Day 1.
Time frame: Up to 3 weeks; first cycle of therapy through the first day of Cycle 2
Population: An initial safety cohort of 10 patients who enrolled and received at least 1 dose of brentuximab vedotin were evaluated for this outcome.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Brentuximab Vedotin + Bendamustine | Incidence of Dose-limiting Toxicities | 0 Participants |
Secondary
Overall Best Response Rate
Percentage of participants who achieved a best response of complete remission (CR, disappearance of all evidence of disease), partial remission (PR, regression of greater than or equal to 50% of measurable disease and no new sites), stable disease (SD, failure to obtain a complete or partial response or progressive disease), or progressive disease (PD, any new lesion or increase by 50% or more of previously involved sites from nadir) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma
Time frame: Up to 4.6 months
Population: All patients who received at least 2 cycles of combination treatment, had a baseline tumor assessment, and at least 1 post-baseline tumor assessment, or who had documented disease progression (including clinical disease progression) any time after the first dose of combination therapy.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brentuximab Vedotin + Bendamustine | Overall Best Response Rate | Complete Remission | 39 Participants |
| Brentuximab Vedotin + Bendamustine | Overall Best Response Rate | Partial Remission | 10 Participants |
| Brentuximab Vedotin + Bendamustine | Overall Best Response Rate | Stable Disease | 3 Participants |
| Brentuximab Vedotin + Bendamustine | Overall Best Response Rate | Progressive Disease | 1 Participants |
Secondary
Progression-free Survival
The time from first dose of study medication to first documentation of disease progression/relapse, or to death due to any cause, whichever occurs first.
Time frame: Up to 49 months
Population: All patients who received at least 2 cycles of combination treatment and had a baseline tumor assessment and at least 1 post-baseline tumor assessment, or who had documented disease progression (including clinical disease progression) at any time after the first dose of combination therapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brentuximab Vedotin + Bendamustine | Progression-free Survival | 44.2 months |