Disease, Hodgkin, Lymphoma, Large-Cell, Anaplastic, Lymphoma, Non-Hodgkin
Conditions
Keywords
Antibodies, Monoclonal, Antibody-Drug Conjugate, Antigens, CD30, Drug Therapy, Hematologic Diseases, Immunotherapy, Monomethylauristatin E
Brief summary
This is a multicenter, open-label study to evaluate the safety and efficacy of treatment with brentuximab vedotin (SGN-35) in patients who have previously participated in an brentuximab vedotin study.
Detailed description
This is a multicenter, open-label study to evaluate single-agent brentuximab vedotin (SGN-35) treatment in patients who previously participated in a brentuximab vedotin study, including Studies SGN35-005 (NCT01100502), SGN35-007 (NCT01026233), and SGN35-008 (NCT01026415). Patients treated on this study (SGN35-006) could re-enroll on study if eligible. The study consisted of 2 arms, as follows: * Retreatment arm: Patients with CD30-positive hematologic malignancies who experienced a complete remission (CR) or partial remission (PR) with previous brentuximab vedotin treatment on a clinical study and subsequently experienced disease progression or relapse. The purpose of this arm was to assess safety and efficacy of retreatment with brentuximab vedotin. * Extension treatment arm: Patients with either CD30-positive hematologic or nonhematologic malignancies who completed treatment in a prior brentuximab vedotin study without unacceptable toxicity and experienced clinical benefit as assessed by the investigator. The purpose of this arm was to enable patients who participated in certain prior brentuximab vedotin trials to receive extension treatment and to assess patient safety and survival in the extension treatment setting.
Interventions
DRUGbrentuximab vedotin
Every 3 weeks by IV infusion (1.2 or 1.8 mg/kg) until disease progression, unacceptable toxicity, or study closure
Sponsors
Millennium Pharmaceuticals, Inc.
Seagen Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participated in a previous brentuximab vedotin study. * CD30-positive hematologic malignancy. * At a minimum, experienced clinical benefit in the prior brentuximab vedotin study. For retreatment, patients must have previously achieved either complete or partial remission with brentuximab vedotin and experienced disease progression after discontinuing the prior brentuximab vedotin study.
Exclusion criteria
Withdrew consent to participate in any prior brentuximab vedotin study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate by Investigator | Up to approximately 38 months | Percentage of participants in the retreatment arm 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. |
| Adverse Events by Severity, Seriousness, and Relationship to Treatment | up to 39 months | Counts of participants who had adverse events or treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose on SGN35-006). 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. |
| Laboratory Abnormalities >/= Grade 3 | Up to 39 months | Counts of study participants with post-baseline 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Objective Response by Kaplan-Meier Analysis | Up to 38 months | Duration of objective response (CR + PR) on retreatment, defined as time of initial response until disease progression or death |
| Incidence of Antitherapeutic Antibodies | Up to 39 months | Counts of participants with anti-brentuximab vedotin antibodies at any time during extension treatment on Study SGN35-006 or number of retreatment experiences with anti-brentuximab vedotin antibodies at any time during retreatment |
| Progression-free Survival by Kaplan-Meier Analysis | Up to approximately 29 months | Progression-free survival, defined as time from start of study treatment in the retreatment arm to disease progression per investigator or death due to any cause |
| Overall Survival | Up to approximately 41 months | Overall survival for both extension and retreatment arms, defined as time from start of study treatment to date of death due to any cause |
Countries
France, United States
Participant flow
Recruitment details
Jul 2009 - Mar 2013
Participants by arm
| Arm | Count |
|---|---|
| BV Extension Brentuximab vedotin 1.2 or 1.8 mg/kg every 3 weeks by IV infusion (continued treatment) | 78 |
| BV Retreatment Brentuximab vedotin 1.2 or 1.8 mg/kg every 3 weeks by IV infusion (retreatment after relapse) | 32 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-up Period | Lost to Follow-up | 7 | 0 |
| Follow-up Period | Patient unavailable for site visits | 1 | 0 |
| Follow-up Period | Re-enrolled for Retreatment | 2 | 3 |
| Follow-up Period | Study Stopped by Sponsor | 40 | 20 |
| Follow-up Period | Withdrawal by Subject | 1 | 0 |
| Treatment Period | Adverse Event | 15 | 9 |
| Treatment Period | Physician Decision | 14 | 6 |
| Treatment Period | Progressive Disease | 33 | 12 |
| Treatment Period | Study Stopped by Sponsor | 4 | 4 |
| Treatment Period | Withdrawal by Subject | 12 | 1 |
Baseline characteristics
| Characteristic | BV Retreatment | Total | BV Extension |
|---|---|---|---|
| Age, Customized | 37 years | 33.5 years | 32 years |
| Disease diagnosis Hodgkin lymphoma (HL) | 21 participants | 89 participants | 68 participants |
| Disease diagnosis Other | 3 participants | 5 participants | 2 participants |
| Disease diagnosis Systemic anaplastic large cell lymphoma (ALCL) | 8 participants | 16 participants | 8 participants |
| Eastern Cooperative Oncology Group Performance Status 0 | 12 participants | 59 participants | 47 participants |
| Eastern Cooperative Oncology Group Performance Status 1 | 18 participants | 48 participants | 30 participants |
| Eastern Cooperative Oncology Group Performance Status 2 | 2 participants | 2 participants | 0 participants |
| Eastern Cooperative Oncology Group Performance Status 3-5 | 0 participants | 0 participants | 0 participants |
| Eastern Cooperative Oncology Group Performance Status Missing | 0 participants | 1 participants | 1 participants |
| Gender Female | 17 Participants | 52 Participants | 35 Participants |
| Gender Male | 15 Participants | 58 Participants | 43 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 11 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 27 Participants | 93 Participants | 66 Participants |
| Region of Enrollment France | 3 participants | 3 participants | 0 participants |
| Region of Enrollment United States | 29 participants | 107 participants | 78 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 75 / 78 | 31 / 32 |
| serious Total, serious adverse events | 16 / 78 | 9 / 32 |
Outcome results
Primary
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 on SGN35-006). 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 39 months
Population: All participants who received treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BV Retreatment - HL | Adverse Events by Severity, Seriousness, and Relationship to Treatment | TEAE with severity grade >/=3 | 37 participants |
| BV Retreatment - HL | Adverse Events by Severity, Seriousness, and Relationship to Treatment | Discontinued treatment due to adverse event | 13 participants |
| BV Retreatment - HL | Adverse Events by Severity, Seriousness, and Relationship to Treatment | Serious adverse event | 16 participants |
| BV Retreatment - HL | Adverse Events by Severity, Seriousness, and Relationship to Treatment | TEAE related to study drug | 65 participants |
| BV Retreatment - HL | Adverse Events by Severity, Seriousness, and Relationship to Treatment | Serious adverse event related to study drug | 10 participants |
| BV Retreatment - HL | Adverse Events by Severity, Seriousness, and Relationship to Treatment | Any TEAE | 75 participants |
| BV Retreatment - ALCL | Adverse Events by Severity, Seriousness, and Relationship to Treatment | Serious adverse event related to study drug | 4 participants |
| BV Retreatment - ALCL | Adverse Events by Severity, Seriousness, and Relationship to Treatment | Any TEAE | 31 participants |
| BV Retreatment - ALCL | Adverse Events by Severity, Seriousness, and Relationship to Treatment | TEAE related to study drug | 27 participants |
| BV Retreatment - ALCL | Adverse Events by Severity, Seriousness, and Relationship to Treatment | Discontinued treatment due to adverse event | 9 participants |
| BV Retreatment - ALCL | Adverse Events by Severity, Seriousness, and Relationship to Treatment | Serious adverse event | 9 participants |
| BV Retreatment - ALCL | Adverse Events by Severity, Seriousness, and Relationship to Treatment | TEAE with severity grade >/=3 | 16 participants |
Primary
Laboratory Abnormalities >/= Grade 3
Counts of study participants with post-baseline 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 39 months
Population: All participants who received treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BV Retreatment - HL | Laboratory Abnormalities >/= Grade 3 | Potassium (low) | 0 participants |
| BV Retreatment - HL | Laboratory Abnormalities >/= Grade 3 | Neutrophils (low) | 7 participants |
| BV Retreatment - HL | Laboratory Abnormalities >/= Grade 3 | Phosphate (low) | 7 participants |
| BV Retreatment - HL | Laboratory Abnormalities >/= Grade 3 | Platelets (low) | 4 participants |
| BV Retreatment - HL | Laboratory Abnormalities >/= Grade 3 | Glucose (high) | 3 participants |
| BV Retreatment - HL | Laboratory Abnormalities >/= Grade 3 | Alanine aminotransferase (high) | 1 participants |
| BV Retreatment - HL | Laboratory Abnormalities >/= Grade 3 | Bilirubin (high) | 0 participants |
| BV Retreatment - HL | Laboratory Abnormalities >/= Grade 3 | Calcium (low) | 0 participants |
| BV Retreatment - HL | Laboratory Abnormalities >/= Grade 3 | Hemoglobin (low) | 1 participants |
| BV Retreatment - HL | Laboratory Abnormalities >/= Grade 3 | Any >/= Grade 3 laboratory abnormality | 29 participants |
| BV Retreatment - HL | Laboratory Abnormalities >/= Grade 3 | Lymphocytes (low) | 16 participants |
| BV Retreatment - HL | Laboratory Abnormalities >/= Grade 3 | Leukocytes (low) | 3 participants |
| BV Retreatment - HL | Laboratory Abnormalities >/= Grade 3 | Aspartate aminotransferase (high) | 1 participants |
| BV Retreatment - HL | Laboratory Abnormalities >/= Grade 3 | Sodium (low) | 2 participants |
| BV Retreatment - ALCL | Laboratory Abnormalities >/= Grade 3 | Calcium (low) | 1 participants |
| BV Retreatment - ALCL | Laboratory Abnormalities >/= Grade 3 | Bilirubin (high) | 1 participants |
| BV Retreatment - ALCL | Laboratory Abnormalities >/= Grade 3 | Any >/= Grade 3 laboratory abnormality | 12 participants |
| BV Retreatment - ALCL | Laboratory Abnormalities >/= Grade 3 | Neutrophils (low) | 3 participants |
| BV Retreatment - ALCL | Laboratory Abnormalities >/= Grade 3 | Hemoglobin (low) | 1 participants |
| BV Retreatment - ALCL | Laboratory Abnormalities >/= Grade 3 | Phosphate (low) | 3 participants |
| BV Retreatment - ALCL | Laboratory Abnormalities >/= Grade 3 | Lymphocytes (low) | 8 participants |
| BV Retreatment - ALCL | Laboratory Abnormalities >/= Grade 3 | Aspartate aminotransferase (high) | 2 participants |
| BV Retreatment - ALCL | Laboratory Abnormalities >/= Grade 3 | Potassium (low) | 1 participants |
| BV Retreatment - ALCL | Laboratory Abnormalities >/= Grade 3 | Glucose (high) | 2 participants |
| BV Retreatment - ALCL | Laboratory Abnormalities >/= Grade 3 | Leukocytes (low) | 3 participants |
| BV Retreatment - ALCL | Laboratory Abnormalities >/= Grade 3 | Platelets (low) | 3 participants |
| BV Retreatment - ALCL | Laboratory Abnormalities >/= Grade 3 | Sodium (low) | 0 participants |
| BV Retreatment - ALCL | Laboratory Abnormalities >/= Grade 3 | Alanine aminotransferase (high) | 1 participants |
Primary
Objective Response Rate by Investigator
Percentage of participants in the retreatment arm 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 approximately 38 months
Population: Any patient who received retreatment and had postbaseline response results; 1 HL patient did not have postbaseline response results and 3 ALCL patients were retreated more than once.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BV Retreatment - HL | Objective Response Rate by Investigator | 60 percentage of retreatment experiences |
| BV Retreatment - ALCL | Objective Response Rate by Investigator | 91 percentage of retreatment experiences |
| BV Retreatment - Other | Objective Response Rate by Investigator | 33 percentage of retreatment experiences |
| BV Retreatment Total | Objective Response Rate by Investigator | 68 percentage of retreatment experiences |
Secondary
Duration of Objective Response by Kaplan-Meier Analysis
Duration of objective response (CR + PR) on retreatment, defined as time of initial response until disease progression or death
Time frame: Up to 38 months
Population: Participants with objective response among those who received retreatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BV Retreatment - HL | Duration of Objective Response by Kaplan-Meier Analysis | 9.2 months |
| BV Retreatment - ALCL | Duration of Objective Response by Kaplan-Meier Analysis | 8.8 months |
| BV Retreatment - Other | Duration of Objective Response by Kaplan-Meier Analysis | NA months |
| BV Retreatment Total | Duration of Objective Response by Kaplan-Meier Analysis | 9.2 months |
Secondary
Incidence of Antitherapeutic Antibodies
Counts of participants with anti-brentuximab vedotin antibodies at any time during extension treatment on Study SGN35-006 or number of retreatment experiences with anti-brentuximab vedotin antibodies at any time during retreatment
Time frame: Up to 39 months
Population: Any patient who received extension treatment or retreatment and had baseline and postbaseline sample results; 1 HL patient on the retreatment arm did not have postbaseline sample results and 3 ALCL patients on the retreatment arm were retreated more than once and had samples.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BV Retreatment - HL | Incidence of Antitherapeutic Antibodies | 15 participants or experiences |
| BV Retreatment - ALCL | Incidence of Antitherapeutic Antibodies | 12 participants or experiences |
Secondary
Overall Survival
Overall survival for both extension and retreatment arms, defined as time from start of study treatment to date of death due to any cause
Time frame: Up to approximately 41 months
Population: Patients who received treatment on the extension arm, and patients who received retreatment and had postbaseline response results; 1 HL patient on the retreatment arm did not have postbaseline response results and 3 ALCL patients on the retreatment arm were retreated more than once.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BV Retreatment - HL | Overall Survival | NA months |
| BV Retreatment - ALCL | Overall Survival | NA months |
| BV Retreatment - Other | Overall Survival | NA months |
| BV Retreatment Total | Overall Survival | NA months |
| BV Retreatment Total | Overall Survival | NA months |
Secondary
Progression-free Survival by Kaplan-Meier Analysis
Progression-free survival, defined as time from start of study treatment in the retreatment arm to disease progression per investigator or death due to any cause
Time frame: Up to approximately 29 months
Population: Any patient who received retreatment and had postbaseline response results; 1 HL patient did not have postbaseline response results and 3 ALCL patients were retreated more than once.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BV Retreatment - HL | Progression-free Survival by Kaplan-Meier Analysis | 9.9 months |
| BV Retreatment - ALCL | Progression-free Survival by Kaplan-Meier Analysis | 12.9 months |
| BV Retreatment - Other | Progression-free Survival by Kaplan-Meier Analysis | 4.4 months |
| BV Retreatment Total | Progression-free Survival by Kaplan-Meier Analysis | 9.9 months |