Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Lymphoma, T-Cell
Conditions
Keywords
Lymphoma, Large B-Cell, Diffuse, Antigens, CD30, Antibody-Drug Conjugate, Antibodies, Monoclonal, Lymphoma, Non-Hodgkin, Monomethyl auristatin E, Drug Therapy, Immunotherapy, Hematologic Diseases, Lymphoma, Lymphoma, B-Cell, Lymphoma, T-Cell
Brief summary
This is an open-label, multicenter, phase 2 clinical trial to evaluate the efficacy and safety of brentuximab vedotin as a single agent in patients with CD30-positive non-Hodgkin lymphoma (NHL) (Part A). The study will also evaluate the safety and efficacy of brentuximab vedotin in combination with rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (Part B) as well as further evaluate correlation of CD30 expression and response in DLBCL (Part C).
Interventions
DRUGbrentuximab vedotin
1.8 mg/kg every 3 weeks by IV infusion
DRUGrituximab
375 mg/m2 every 3 weeks by IV infusion
Sponsors
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
* Histologically-confirmed NHL (DLBCL only for Parts B and C) * Relapsed or refractory disease following at least 1 prior systemic therapy * Measurable disease of at least 1.5 cm as documented by CT * Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
Exclusion criteria
* History of another primary invasive malignancy that has not been in remission for at least 3 years * Current diagnosis of systemic or cutaneous anaplastic large cell lymphoma or mycosis fungoides * B cell lymphoma previously treated with only single-agent rituximab (for patients receiving brentuximab vedotin only) or corticosteroids as monotherapy * Known cerebral/meningeal disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) by Investigator With Brentuximab Vedotin Monotherapy | Up to approximately 3 years | Percentage of participants treated with brentuximab vedotin monotherapy 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 With Brentuximab Vedotin Plus Rituximab | Up to 3 years | Counts of participants who had treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose on Study SGN35-012). Serious adverse events are reported from the time of informed consent. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.03) were used to assess severity (1=mild, 2=moderate, 3=severe, 4=life-threatening/disabling, 5=fatal). 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Remission (CR) Rate by Investigator | Up to approximately 3 years | Percentage of participants treated with brentuximab vedotin monotherapy or brentuximab vedotin plus rituximab who achieved a best response of complete remission (CR, disappearance of all evidence of disease) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma. |
| Duration of Objective Response With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis | Up to approximately 3 years | Duration of complete remission (CR) or partial remission (PR), defined as time of initial response until disease progression or death. Response criteria per Cheson 2007 Revised Response Criteria for Malignant Lymphoma. |
| Progression-Free Survival With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis | Up to approximately 3 years | Progression-free survival, defined as time from start of study treatment to disease progression per investigator or death due to any cause |
| Correlation Between Antitumor Activity of Brentuximab Vedotin Monotherapy and CD30 Expression | Up to 3 years | Percentage of participants treated with brentuximab vedotin monotherapy 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), or stable disease (SD, no new sites and no change in size of previous lesions) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma. Patients are grouped by CD30-positivity or CD30u (undetectable CD30). |
| Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | Up to 3 years | Counts of participants who had treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose on Study SGN35-012). Serious adverse events are reported from the time of informed consent. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.03) were used to assess severity (1=mild, 2=moderate, 3=severe, 4=life-threatening/disabling, 5=fatal). 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. |
| Duration of Complete Remission With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis | Up to approximately 3 years | Duration of complete remission (CR), defined as time of initial response until disease progression or death. Response criteria per Cheson 2007 Revised Response Criteria for Malignant Lymphoma. |
| Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Trough Concentration (Ctrough) (Cycle 1) | 3 weeks | Trough concentration of ADC from 0 to 21 days following the first dose of brentuximab vedotin |
| Maximum Concentration (Cmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE) (Cycle 1) | 3 weeks | Maximum serum concentration of MMAE from 0 to 21 days following the first dose of brentuximab vedotin |
| Time to Maximum Concentration (Tmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE) | 3 weeks | Time of maximum serum concentration of MMAE from 0 to 21 days following the first dose of brentuximab vedotin |
| Baseline Soluble CD30 Expression | Baseline | Serum concentration of soluble CD30 before first dose of brentuximab vedotin |
| Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Concentration at End of Infusion (Ceoi) (Cycle 1) | 1 day | End of infusion concentration of ADC following the first dose of brentuximab vedotin |
| Objective Response Rate (ORR) by Investigator With Brentuximab Vedotin Plus Rituximab | Up to approximately 3 years | Percentage of participants treated with brentuximab vedotin plus rituximab 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. |
Countries
Canada, United States
Participant flow
Recruitment details
Aug 2011 - Jun 2015
Pre-assignment details
Four additional patients enrolled, but withdrew prior to receiving treatment.
Participants by arm
| Arm | Count |
|---|---|
| CD30+ T-Cell NHL, BV | 35 |
| CD30+ B-Cell NHL, BV | 68 |
| CD30u DLBCL, BV | 53 |
| CD30+ DLBCL, BV+R | 16 |
| Total | 172 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 2 | 1 |
Baseline characteristics
| Characteristic | CD30+ B-Cell NHL, BV | CD30u DLBCL, BV | CD30+ T-Cell NHL, BV | CD30+ DLBCL, BV+R | Total |
|---|---|---|---|---|---|
| Age, Continuous | 57 years | 65 years | 64 years | 62 years | 63 years |
| Bulky Disease (≥5 cm on at least one baseline index lesion) No | 41 participants | 18 participants | 30 participants | 12 participants | 101 participants |
| Bulky Disease (≥5 cm on at least one baseline index lesion) Yes | 27 participants | 35 participants | 5 participants | 4 participants | 71 participants |
| % CD30 Expression by Visual Immunohistochemistry (vIHC) | 35 percentage | 0 percentage | 15 percentage | 50 percentage | 8 percentage |
| Disease Stage Stage I | 4 participants | 1 participants | 2 participants | 1 participants | 8 participants |
| Disease Stage Stage II | 12 participants | 7 participants | 2 participants | 3 participants | 24 participants |
| Disease Stage Stage III | 17 participants | 11 participants | 13 participants | 6 participants | 47 participants |
| Disease Stage Stage IV | 31 participants | 33 participants | 14 participants | 6 participants | 84 participants |
| Disease Stage Unknown | 4 participants | 1 participants | 4 participants | 0 participants | 9 participants |
| Disease Status Relative to Most Recent Prior Therapy Missing | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Disease Status Relative to Most Recent Prior Therapy Refractory | 55 participants | 37 participants | 22 participants | 9 participants | 123 participants |
| Disease Status Relative to Most Recent Prior Therapy Relapsed | 12 participants | 16 participants | 13 participants | 7 participants | 48 participants |
| Eastern Cooperative Oncology Group Performance Status (ECOG) 0 | 25 participants | 10 participants | 7 participants | 9 participants | 51 participants |
| Eastern Cooperative Oncology Group Performance Status (ECOG) 1 | 35 participants | 31 participants | 23 participants | 7 participants | 96 participants |
| Eastern Cooperative Oncology Group Performance Status (ECOG) 2 | 7 participants | 12 participants | 5 participants | 0 participants | 24 participants |
| Eastern Cooperative Oncology Group Performance Status (ECOG) 3-5 | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Eastern Cooperative Oncology Group Performance Status (ECOG) Missing | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 7 Participants | 3 Participants | 1 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 65 Participants | 46 Participants | 32 Participants | 15 Participants | 158 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Pathological Diagnosis Angioimmunoblastic T-cell Lymphoma | 0 participants | 0 participants | 13 participants | 0 participants | 13 participants |
| Pathological Diagnosis Diffuse Large B-Cell Lymphoma (DLBCL) | 43 participants | 53 participants | 0 participants | 16 participants | 112 participants |
| Pathological Diagnosis Epstein-Barr Virus-Associated DLBCL of Elderly | 5 participants | 0 participants | 0 participants | 0 participants | 5 participants |
| Pathological Diagnosis Follicular Lymphoma | 3 participants | 0 participants | 0 participants | 0 participants | 3 participants |
| Pathological Diagnosis Gray Zone Lymphoma | 6 participants | 0 participants | 0 participants | 0 participants | 6 participants |
| Pathological Diagnosis Peripheral T-Cell Lymphoma Not Otherwise Specified | 0 participants | 0 participants | 22 participants | 0 participants | 22 participants |
| Pathological Diagnosis Plasmablastic Lymphoma | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Pathological Diagnosis Post-Transplant Lymphoproliferative Disorder | 3 participants | 0 participants | 0 participants | 0 participants | 3 participants |
| Pathological Diagnosis Primary Mediastinal B-Cell Lymphoma | 6 participants | 0 participants | 0 participants | 0 participants | 6 participants |
| Pathological Diagnosis T-Cell Rich B-Cell Lymphoma | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 4 Participants | 1 Participants | 0 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 4 Participants | 5 Participants | 0 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 2 Participants | 0 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 55 Participants | 41 Participants | 29 Participants | 15 Participants | 140 Participants |
| Refractory to Frontline Therapy Missing/Unknown | 2 participants | 0 participants | 0 participants | 0 participants | 2 participants |
| Refractory to Frontline Therapy No | 15 participants | 19 participants | 10 participants | 6 participants | 50 participants |
| Refractory to Frontline Therapy Yes | 51 participants | 34 participants | 25 participants | 10 participants | 120 participants |
| Sex: Female, Male Female | 29 Participants | 27 Participants | 8 Participants | 4 Participants | 68 Participants |
| Sex: Female, Male Male | 39 Participants | 26 Participants | 27 Participants | 12 Participants | 104 Participants |
| Transformed Disease from Prior Non-Hodgkin Lymphoma No | 54 participants | 42 participants | 34 participants | 11 participants | 141 participants |
| Transformed Disease from Prior Non-Hodgkin Lymphoma Yes | 14 participants | 11 participants | 1 participants | 5 participants | 31 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 96 / 103 | 48 / 53 | 15 / 16 |
| serious Total, serious adverse events | 49 / 103 | 22 / 53 | 3 / 16 |
Outcome results
Primary
Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Plus Rituximab
Counts of participants who had treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose on Study SGN35-012). Serious adverse events are reported from the time of informed consent. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.03) were used to assess severity (1=mild, 2=moderate, 3=severe, 4=life-threatening/disabling, 5=fatal). 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 3 years
Population: All participants who received treatment with brentuximab vedotin plus rituximab.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CD30+ T-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Plus Rituximab | Any TEAE | 16 participants |
| CD30+ T-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Plus Rituximab | TEAE Related to Study Drug | 15 participants |
| CD30+ T-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Plus Rituximab | TEAE With Severity Grade >/=3 | 9 participants |
| CD30+ T-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Plus Rituximab | Discontinued Treatment Due to Adverse Event | 2 participants |
| CD30+ T-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Plus Rituximab | Serious Adverse Event | 3 participants |
| CD30+ T-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Plus Rituximab | Serious Adverse Event Related to Study Drug | 3 participants |
| CD30+ T-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Plus Rituximab | Deaths (Within 30 Days of Last Dose) | 1 participants |
| CD30+ T-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Plus Rituximab | Chemistry Laboratory Abnormalities >/=Grade 3 | 1 participants |
| CD30+ T-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Plus Rituximab | Hematology Laboratory Abnormalities >/=Grade 3 | 7 participants |
Primary
Objective Response Rate (ORR) by Investigator With Brentuximab Vedotin Monotherapy
Percentage of participants treated with brentuximab vedotin monotherapy 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 3 years
Population: All participants who received treatment with brentuximab vedotin monotherapy and had both a baseline and at least one post-baseline disease assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CD30+ T-Cell NHL, BV | Objective Response Rate (ORR) by Investigator With Brentuximab Vedotin Monotherapy | 41 percentage of participants |
| CD30+ Other B-Cell NHL, BV | Objective Response Rate (ORR) by Investigator With Brentuximab Vedotin Monotherapy | 26 percentage of participants |
| CD30+ DLBCL, BV | Objective Response Rate (ORR) by Investigator With Brentuximab Vedotin Monotherapy | 44 percentage of participants |
| CD30u DLBCL, BV | Objective Response Rate (ORR) by Investigator With Brentuximab Vedotin Monotherapy | 31 percentage of participants |
Secondary
Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy
Counts of participants who had treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose on Study SGN35-012). Serious adverse events are reported from the time of informed consent. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.03) were used to assess severity (1=mild, 2=moderate, 3=severe, 4=life-threatening/disabling, 5=fatal). 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 3 years
Population: All participants who received treatment with brentuximab vedotin monotherapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CD30+ T-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | Discontinued Treatment Due To Adverse Event | 6 participants |
| CD30+ T-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | Hematology Laboratory Abnormalities >/= Grade 3 | 11 participants |
| CD30+ T-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | Serious Adverse Event Related to Study Drug | 5 participants |
| CD30+ T-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | Serious Adverse Event | 15 participants |
| CD30+ T-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | Any TEAE | 32 participants |
| CD30+ T-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | Chemistry Laboratory Abnormalities >/= Grade 3 | 8 participants |
| CD30+ T-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | TEAE With Severity Grade >/=3 | 23 participants |
| CD30+ T-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | TEAE Related to Study Drug | 28 participants |
| CD30+ T-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | Deaths (Within 30 Days of Last Dose) | 3 participants |
| CD30+ Other B-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | Serious Adverse Event | 34 participants |
| CD30+ Other B-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | Any TEAE | 66 participants |
| CD30+ Other B-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | TEAE Related to Study Drug | 62 participants |
| CD30+ Other B-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | TEAE With Severity Grade >/=3 | 52 participants |
| CD30+ Other B-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | Discontinued Treatment Due To Adverse Event | 7 participants |
| CD30+ Other B-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | Serious Adverse Event Related to Study Drug | 15 participants |
| CD30+ Other B-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | Deaths (Within 30 Days of Last Dose) | 5 participants |
| CD30+ Other B-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | Chemistry Laboratory Abnormalities >/= Grade 3 | 16 participants |
| CD30+ Other B-Cell NHL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | Hematology Laboratory Abnormalities >/= Grade 3 | 31 participants |
| CD30+ DLBCL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | TEAE With Severity Grade >/=3 | 37 participants |
| CD30+ DLBCL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | Any TEAE | 52 participants |
| CD30+ DLBCL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | Deaths (Within 30 Days of Last Dose) | 6 participants |
| CD30+ DLBCL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | TEAE Related to Study Drug | 39 participants |
| CD30+ DLBCL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | Hematology Laboratory Abnormalities >/= Grade 3 | 21 participants |
| CD30+ DLBCL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | Serious Adverse Event | 22 participants |
| CD30+ DLBCL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | Discontinued Treatment Due To Adverse Event | 4 participants |
| CD30+ DLBCL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | Chemistry Laboratory Abnormalities >/= Grade 3 | 10 participants |
| CD30+ DLBCL, BV | Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy | Serious Adverse Event Related to Study Drug | 7 participants |
Secondary
Baseline Soluble CD30 Expression
Serum concentration of soluble CD30 before first dose of brentuximab vedotin
Time frame: Baseline
Population: All patients who were treated with brentuximab vedotin monotherapy and had baseline sCD30 expression results.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CD30+ T-Cell NHL, BV | Baseline Soluble CD30 Expression | 1005.4 ng/mL |
| CD30+ Other B-Cell NHL, BV | Baseline Soluble CD30 Expression | 229.4 ng/mL |
| CD30+ DLBCL, BV | Baseline Soluble CD30 Expression | 140.4 ng/mL |
Secondary
Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Concentration at End of Infusion (Ceoi) (Cycle 1)
End of infusion concentration of ADC following the first dose of brentuximab vedotin
Time frame: 1 day
Population: All patients who were treated with brentuximab vedotin monotherapy and had Ceoi of ADC results.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| CD30+ T-Cell NHL, BV | Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Concentration at End of Infusion (Ceoi) (Cycle 1) | 35.6 ug/mL | Geometric Coefficient of Variation 25 |
| CD30+ Other B-Cell NHL, BV | Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Concentration at End of Infusion (Ceoi) (Cycle 1) | 40.0 ug/mL | Geometric Coefficient of Variation 29 |
| CD30+ DLBCL, BV | Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Concentration at End of Infusion (Ceoi) (Cycle 1) | 40.1 ug/mL | Geometric Coefficient of Variation 43 |
Secondary
Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Trough Concentration (Ctrough) (Cycle 1)
Trough concentration of ADC from 0 to 21 days following the first dose of brentuximab vedotin
Time frame: 3 weeks
Population: All patients who were treated with brentuximab vedotin monotherapy and had Ctrough of ADC results.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| CD30+ T-Cell NHL, BV | Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Trough Concentration (Ctrough) (Cycle 1) | 0.44 ug/mL | Geometric Coefficient of Variation 113 |
| CD30+ Other B-Cell NHL, BV | Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Trough Concentration (Ctrough) (Cycle 1) | 0.91 ug/mL | Geometric Coefficient of Variation 119 |
| CD30+ DLBCL, BV | Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Trough Concentration (Ctrough) (Cycle 1) | 0.86 ug/mL | Geometric Coefficient of Variation 94 |
Secondary
Complete Remission (CR) Rate by Investigator
Percentage of participants treated with brentuximab vedotin monotherapy or brentuximab vedotin plus rituximab who achieved a best response of complete remission (CR, disappearance of all evidence of disease) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Time frame: Up to approximately 3 years
Population: All participants who received brentuximab vedotin monotherapy or brentuximab vedotin plus rituximab and had both a baseline and at least one post-baseline disease assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CD30+ T-Cell NHL, BV | Complete Remission (CR) Rate by Investigator | 24 percentage of participants |
| CD30+ Other B-Cell NHL, BV | Complete Remission (CR) Rate by Investigator | 16 percentage of participants |
| CD30+ DLBCL, BV | Complete Remission (CR) Rate by Investigator | 19 percentage of participants |
| CD30u DLBCL, BV | Complete Remission (CR) Rate by Investigator | 12 percentage of participants |
| CD30+ DLBCL, BV+R | Complete Remission (CR) Rate by Investigator | 17 percentage of participants |
Secondary
Correlation Between Antitumor Activity of Brentuximab Vedotin Monotherapy and CD30 Expression
Percentage of participants treated with brentuximab vedotin monotherapy 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), or stable disease (SD, no new sites and no change in size of previous lesions) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma. Patients are grouped by CD30-positivity or CD30u (undetectable CD30).
Time frame: Up to 3 years
Population: All participants who received treatment with brentuximab vedotin monotherapy and had both a baseline and at least one post-baseline disease assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CD30+ T-Cell NHL, BV | Correlation Between Antitumor Activity of Brentuximab Vedotin Monotherapy and CD30 Expression | Complete Remission (CR) | 24 percentage of participants |
| CD30+ T-Cell NHL, BV | Correlation Between Antitumor Activity of Brentuximab Vedotin Monotherapy and CD30 Expression | Disease Control Rate (CR+PR+SD) | 59 percentage of participants |
| CD30+ T-Cell NHL, BV | Correlation Between Antitumor Activity of Brentuximab Vedotin Monotherapy and CD30 Expression | Partial Remission (PR) | 18 percentage of participants |
| CD30+ Other B-Cell NHL, BV | Correlation Between Antitumor Activity of Brentuximab Vedotin Monotherapy and CD30 Expression | Complete Remission (CR) | 16 percentage of participants |
| CD30+ Other B-Cell NHL, BV | Correlation Between Antitumor Activity of Brentuximab Vedotin Monotherapy and CD30 Expression | Disease Control Rate (CR+PR+SD) | 63 percentage of participants |
| CD30+ Other B-Cell NHL, BV | Correlation Between Antitumor Activity of Brentuximab Vedotin Monotherapy and CD30 Expression | Partial Remission (PR) | 11 percentage of participants |
| CD30+ DLBCL, BV | Correlation Between Antitumor Activity of Brentuximab Vedotin Monotherapy and CD30 Expression | Partial Remission (PR) | 25 percentage of participants |
| CD30+ DLBCL, BV | Correlation Between Antitumor Activity of Brentuximab Vedotin Monotherapy and CD30 Expression | Complete Remission (CR) | 19 percentage of participants |
| CD30+ DLBCL, BV | Correlation Between Antitumor Activity of Brentuximab Vedotin Monotherapy and CD30 Expression | Disease Control Rate (CR+PR+SD) | 69 percentage of participants |
| CD30u DLBCL, BV | Correlation Between Antitumor Activity of Brentuximab Vedotin Monotherapy and CD30 Expression | Complete Remission (CR) | 12 percentage of participants |
| CD30u DLBCL, BV | Correlation Between Antitumor Activity of Brentuximab Vedotin Monotherapy and CD30 Expression | Disease Control Rate (CR+PR+SD) | 42 percentage of participants |
| CD30u DLBCL, BV | Correlation Between Antitumor Activity of Brentuximab Vedotin Monotherapy and CD30 Expression | Partial Remission (PR) | 19 percentage of participants |
Secondary
Duration of Complete Remission With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis
Duration of complete remission (CR), defined as time of initial response until disease progression or death. Response criteria per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Time frame: Up to approximately 3 years
Population: All participants who received treatment with brentuximab vedotin monotherapy and achieved CR
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CD30+ T-Cell NHL, BV | Duration of Complete Remission With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis | NA months |
| CD30+ Other B-Cell NHL, BV | Duration of Complete Remission With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis | 7.2 months |
| CD30+ DLBCL, BV | Duration of Complete Remission With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis | NA months |
| CD30u DLBCL, BV | Duration of Complete Remission With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis | 11.6 months |
Secondary
Duration of Objective Response With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis
Duration of complete remission (CR) or partial remission (PR), defined as time of initial response until disease progression or death. Response criteria per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Time frame: Up to approximately 3 years
Population: All participants who received treatment with brentuximab vedotin monotherapy and achieved a CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CD30+ T-Cell NHL, BV | Duration of Objective Response With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis | 7.6 months |
| CD30+ Other B-Cell NHL, BV | Duration of Objective Response With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis | 1.6 months |
| CD30+ DLBCL, BV | Duration of Objective Response With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis | 4.7 months |
| CD30u DLBCL, BV | Duration of Objective Response With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis | 4.7 months |
Secondary
Maximum Concentration (Cmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE) (Cycle 1)
Maximum serum concentration of MMAE from 0 to 21 days following the first dose of brentuximab vedotin
Time frame: 3 weeks
Population: All patients who were treated with brentuximab vedotin monotherapy and had Cmax of MMAE results.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| CD30+ T-Cell NHL, BV | Maximum Concentration (Cmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE) (Cycle 1) | 4.71 ng/mL | Geometric Coefficient of Variation 63 |
| CD30+ Other B-Cell NHL, BV | Maximum Concentration (Cmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE) (Cycle 1) | 4.66 ng/mL | Geometric Coefficient of Variation 88 |
| CD30+ DLBCL, BV | Maximum Concentration (Cmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE) (Cycle 1) | 3.95 ng/mL | Geometric Coefficient of Variation 74 |
Secondary
Objective Response Rate (ORR) by Investigator With Brentuximab Vedotin Plus Rituximab
Percentage of participants treated with brentuximab vedotin plus rituximab 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 3 years
Population: All participants who received treatment with brentuximab vedotin plus rituximab and had both a baseline and at least one post-baseline disease assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CD30+ T-Cell NHL, BV | Objective Response Rate (ORR) by Investigator With Brentuximab Vedotin Plus Rituximab | 50 percentage of participants |
Secondary
Progression-Free Survival With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis
Progression-free survival, defined as time from start of study treatment to disease progression per investigator or death due to any cause
Time frame: Up to approximately 3 years
Population: All participants who received treatment with brentuximab vedotin monotherapy and had both a baseline and at least one post-baseline disease assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CD30+ T-Cell NHL, BV | Progression-Free Survival With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis | 2.5 months |
| CD30+ Other B-Cell NHL, BV | Progression-Free Survival With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis | 2.9 months |
| CD30+ DLBCL, BV | Progression-Free Survival With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis | 4.0 months |
| CD30u DLBCL, BV | Progression-Free Survival With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis | 1.4 months |
Secondary
Time to Maximum Concentration (Tmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE)
Time of maximum serum concentration of MMAE from 0 to 21 days following the first dose of brentuximab vedotin
Time frame: 3 weeks
Population: All patients who were treated with brentuximab vedotin monotherapy and had Tmax of MMAE results.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CD30+ T-Cell NHL, BV | Time to Maximum Concentration (Tmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE) | 1.90 days |
| CD30+ Other B-Cell NHL, BV | Time to Maximum Concentration (Tmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE) | 1.91 days |
| CD30+ DLBCL, BV | Time to Maximum Concentration (Tmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE) | 1.94 days |