Disease, Hodgkin
Conditions
Keywords
Antigens, CD30, Antibody-Drug Conjugate, Antibodies, Monoclonal, Disease, Hodgkin, Hematologic Diseases, Lymphoma, monomethylauristatin E, Drug Therapy, Immunotherapy
Brief summary
This is a single-arm, open-label, multicenter, pivotal clinical trial to evaluate the efficacy and safety of brentuximab vedotin (SGN-35) as a single agent in patients with relapsed or refractory Hodgkin lymphoma.
Interventions
DRUGbrentuximab vedotin
1.8 mg/kg every 3 weeks by intravenous infusion
Sponsors
Millennium Pharmaceuticals, Inc.
Seagen Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with relapsed or refractory Hodgkin lymphoma who have previously received autologous stem cell transplant. * Histologically confirmed CD30-positive disease; tissue from the most recent post diagnostic biopsy of relapsed/refractory disease must be available for confirmation of CD30 expression via slides or tumor block. * Fluorodeoxyglucose-avid disease by positron emission tomography and measurable disease of at least 1.5 cm as documented by spiral computed tomography. * At US sites patients greater than or equal to 12 years of age may be enrolled. At non-US sites patients must be greater than or equal to 18 years of age.
Exclusion criteria
* Previous treatment with brentuximab vedotin. * Previously received an allogeneic transplant. * Congestive heart failure, Class III or IV, by the New York Heart Association criteria. * History of another primary malignancy that has not been in remission for at least 3 years. * Known cerebral/meningeal disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate by Independent Review Group | up to 12 months | Percentage of participants who achieved a best response of complete remission (CR, disappearance of all evidence of disease) or partial remission (PR, regression of greater than or equal to 50% of measurable disease and no new sites) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Remission Rate by Independent Review Group | up to 12 months | Percentage of participants who achieved a best response of CR (disappearance of all evidence of disease) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma. |
| Duration of Objective Response by Kaplan-Meier Analysis | up to approximately 4 years | Duration of objective response (CR + PR) by independent review group, defined as time of initial response until disease progression or death. |
| Duration of Objective Response in Participants With Complete Remission by Kaplan-Meier Analysis | up to approximately 4 years | Duration of response from start of first objective tumor response (CR or PR) by independent review group to disease progression or death due to any cause in participants with CR. |
| Progression-free Survival by Kaplan-Meier Analysis | up to approximately 4 years | Time from start of study treatment to disease progression per independent review group or death due to any cause. |
| Overall Survival | up to approximately 6 years | Time from start of study treatment to date of death due to any cause. |
| Hematology Laboratory Abnormalities >/= Grade 3 | up to 12 months | Counts of study participants with post-baseline hematology laboratory abnormalities of Grade 3 or greater per NCI CTCAE version 3.0. Participants with multiple occurrences of a laboratory abnormality within a category are counted once in that category. |
| Chemistry Laboratory Abnormalities >/= Grade 3 | up to 12 months | Counts of study participants with post-baseline chemistry laboratory abnormalities of Grade 3 or greater per NCI CTCAE version 3.0. Participants with multiple occurrences of a laboratory abnormality within a category are counted once in that category. |
| Area Under the Curve | 3 weeks | Area under the serum concentration-time curve from time 0 to 21 days following the first dose of brentuximab vedotin |
| Maximum Serum Concentration | 3 weeks | Maximum serum concentration from 0 to 21 days following the first dose of brentuximab vedotin |
| Time of Maximum Serum Concentration | 3 weeks | Time of maximum serum concentration from 0 to 21 days following the first dose of brentuximab vedotin |
| Adverse Events by Severity, Seriousness, and Relationship to Treatment | up to 12 months | Counts of participants who had adverse events or treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose). Serious adverse events are reported from the time of informed consent. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 3.0) were used to assess severity (1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death). Relatedness to study drug was assessed by the investigator (Yes/No). Participants with multiple occurrences of an adverse event within a category are counted once within the category. |
Other
| Measure | Time frame | Description |
|---|---|---|
| B Symptom Resolution | up to 12 months | Percentage of participants with lymphoma-related symptoms (B symptoms: fever, night sweats, or weight loss \>10%) at baseline who achieved resolution of all B symptoms at any time during the treatment period. |
Countries
Belgium, Canada, France, Italy, United States
Participant flow
Recruitment details
Enrollment period: Feb 2009 - Aug 2009
Participants by arm
| Arm | Count |
|---|---|
| Brentuximab Vedotin Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion | 102 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Follow-up Period | Lost to Follow-up | 7 |
| Follow-up Period | Other | 2 |
| Follow-up Period | Withdrawal by Subject | 3 |
| Treatment Period | Adverse Event | 20 |
| Treatment Period | Physician Decision | 12 |
| Treatment Period | Progressive disease | 45 |
| Treatment Period | Withdrawal by Subject | 7 |
Baseline characteristics
| Characteristic | Brentuximab Vedotin |
|---|---|
| Age, Customized | 31.0 years |
| Eastern Cooperative Oncology Group Performance Status 0 | 42 participants |
| Eastern Cooperative Oncology Group Performance Status 1 | 60 participants |
| Eastern Cooperative Oncology Group Performance Status 2-5 | 0 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants |
| Race (NIH/OMB) Black or African American | 5 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 | 1 Participants |
| Race (NIH/OMB) White | 89 Participants |
| Sex: Female, Male Female | 54 Participants |
| Sex: Female, Male Male | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 97 / 102 |
| serious Total, serious adverse events | 25 / 102 |
Outcome results
Primary
Objective Response Rate by Independent Review Group
Percentage of participants who achieved a best response of complete remission (CR, disappearance of all evidence of disease) or partial remission (PR, regression of greater than or equal to 50% of measurable disease and no new sites) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Time frame: up to 12 months
Population: Intention to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brentuximab Vedotin | Objective Response Rate by Independent Review Group | 75 percent of participants |
Secondary
Adverse Events by Severity, Seriousness, and Relationship to Treatment
Counts of participants who had adverse events or treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose). Serious adverse events are reported from the time of informed consent. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 3.0) were used to assess severity (1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death). Relatedness to study drug was assessed by the investigator (Yes/No). Participants with multiple occurrences of an adverse event within a category are counted once within the category.
Time frame: up to 12 months
Population: All participants who received treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brentuximab Vedotin | Adverse Events by Severity, Seriousness, and Relationship to Treatment | Any TEAE | 100 participants |
| Brentuximab Vedotin | Adverse Events by Severity, Seriousness, and Relationship to Treatment | TEAE related to study drug | 94 participants |
| Brentuximab Vedotin | Adverse Events by Severity, Seriousness, and Relationship to Treatment | TEAE with severity grade >/=3 | 56 participants |
| Brentuximab Vedotin | Adverse Events by Severity, Seriousness, and Relationship to Treatment | Serious adverse event | 25 participants |
| Brentuximab Vedotin | Adverse Events by Severity, Seriousness, and Relationship to Treatment | Serious adverse event related to study drug | 14 participants |
| Brentuximab Vedotin | Adverse Events by Severity, Seriousness, and Relationship to Treatment | Discontinued treatment due to adverse event | 20 participants |
Secondary
Area Under the Curve
Area under the serum concentration-time curve from time 0 to 21 days following the first dose of brentuximab vedotin
Time frame: 3 weeks
Population: All participants who received treatment
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Brentuximab Vedotin | Area Under the Curve | 88 day * microgram/mL | Geometric Coefficient of Variation 46 |
Secondary
Chemistry Laboratory Abnormalities >/= Grade 3
Counts of study participants with post-baseline chemistry laboratory abnormalities of Grade 3 or greater per NCI CTCAE version 3.0. Participants with multiple occurrences of a laboratory abnormality within a category are counted once in that category.
Time frame: up to 12 months
Population: All participants who received treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brentuximab Vedotin | Chemistry Laboratory Abnormalities >/= Grade 3 | Any >/= Grade 3 chemistry laboratory abnormality | 14 participants |
| Brentuximab Vedotin | Chemistry Laboratory Abnormalities >/= Grade 3 | Alanine aminotransferase (high) | 1 participants |
| Brentuximab Vedotin | Chemistry Laboratory Abnormalities >/= Grade 3 | Albumin (low) | 1 participants |
| Brentuximab Vedotin | Chemistry Laboratory Abnormalities >/= Grade 3 | Calcium (low) | 1 participants |
| Brentuximab Vedotin | Chemistry Laboratory Abnormalities >/= Grade 3 | Glucose (high) | 7 participants |
| Brentuximab Vedotin | Chemistry Laboratory Abnormalities >/= Grade 3 | Potassium (low) | 2 participants |
| Brentuximab Vedotin | Chemistry Laboratory Abnormalities >/= Grade 3 | Sodium (high) | 1 participants |
| Brentuximab Vedotin | Chemistry Laboratory Abnormalities >/= Grade 3 | Urate (high) | 1 participants |
Secondary
Complete Remission Rate by Independent Review Group
Percentage of participants who achieved a best response of CR (disappearance of all evidence of disease) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Time frame: up to 12 months
Population: Intention to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brentuximab Vedotin | Complete Remission Rate by Independent Review Group | 33 percent of participants |
Secondary
Duration of Objective Response by Kaplan-Meier Analysis
Duration of objective response (CR + PR) by independent review group, defined as time of initial response until disease progression or death.
Time frame: up to approximately 4 years
Population: Participants with objective response among the intention to treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brentuximab Vedotin | Duration of Objective Response by Kaplan-Meier Analysis | 6.7 months |
Secondary
Duration of Objective Response in Participants With Complete Remission by Kaplan-Meier Analysis
Duration of response from start of first objective tumor response (CR or PR) by independent review group to disease progression or death due to any cause in participants with CR.
Time frame: up to approximately 4 years
Population: Participants with complete remission among the intention to treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brentuximab Vedotin | Duration of Objective Response in Participants With Complete Remission by Kaplan-Meier Analysis | 27.9 months |
Secondary
Hematology Laboratory Abnormalities >/= Grade 3
Counts of study participants with post-baseline hematology laboratory abnormalities of Grade 3 or greater per NCI CTCAE version 3.0. Participants with multiple occurrences of a laboratory abnormality within a category are counted once in that category.
Time frame: up to 12 months
Population: All participants who received treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brentuximab Vedotin | Hematology Laboratory Abnormalities >/= Grade 3 | Any >/= Grade 3 hematology laboratory abnormality | 35 participants |
| Brentuximab Vedotin | Hematology Laboratory Abnormalities >/= Grade 3 | Hemoglobin (low) | 7 participants |
| Brentuximab Vedotin | Hematology Laboratory Abnormalities >/= Grade 3 | Leukocytes (low) | 6 participants |
| Brentuximab Vedotin | Hematology Laboratory Abnormalities >/= Grade 3 | Lymphocytes (low) | 20 participants |
| Brentuximab Vedotin | Hematology Laboratory Abnormalities >/= Grade 3 | Neutrophils (low) | 12 participants |
| Brentuximab Vedotin | Hematology Laboratory Abnormalities >/= Grade 3 | Platelets (low) | 7 participants |
Secondary
Maximum Serum Concentration
Maximum serum concentration from 0 to 21 days following the first dose of brentuximab vedotin
Time frame: 3 weeks
Population: All participants who received treatment
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Brentuximab Vedotin | Maximum Serum Concentration | 35 microgram/mL | Geometric Coefficient of Variation 17 |
Secondary
Overall Survival
Time from start of study treatment to date of death due to any cause.
Time frame: up to approximately 6 years
Population: Intention to treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brentuximab Vedotin | Overall Survival | 40.5 months |
Secondary
Progression-free Survival by Kaplan-Meier Analysis
Time from start of study treatment to disease progression per independent review group or death due to any cause.
Time frame: up to approximately 4 years
Population: Intention to treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brentuximab Vedotin | Progression-free Survival by Kaplan-Meier Analysis | 5.6 months |
Secondary
Time of Maximum Serum Concentration
Time of maximum serum concentration from 0 to 21 days following the first dose of brentuximab vedotin
Time frame: 3 weeks
Population: All participants who received treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brentuximab Vedotin | Time of Maximum Serum Concentration | 0.02 days |
Other Pre-specified
B Symptom Resolution
Percentage of participants with lymphoma-related symptoms (B symptoms: fever, night sweats, or weight loss \>10%) at baseline who achieved resolution of all B symptoms at any time during the treatment period.
Time frame: up to 12 months
Population: Participants with B symptoms at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brentuximab Vedotin | B Symptom Resolution | 77 percent of participants |