Hodgkin Disease
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of Nivolumab in previously treated (cohorts, A, B & C) or newly diagnosed (cohort D) classical Hodgkin Lymphoma participants.
Interventions
DRUGNivolumab
Specified dose on specified days
DRUGDoxorubicin
Specified dose on specified days
DRUGVinblastine
Specified dose on specified days
DRUGDacarbazine
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
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
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Must have received prior high-dose conditioning chemotherapy followed by autologous stem cell transplant (ASCT) as a part of salvage therapy for cHL (cohort A, B & C - enrollment closed) * Participants may be Brentuximab vedotin- naïve, or may have had prior Brentuximab vedotin treatment (cohort A, B & C - enrollment closed) * Newly diagnosed and previously untreated classical Hodgkin Lymphoma (cohort D)
Exclusion criteria
* Known central nervous system lymphoma * Participants with nodular lymphocyte-predominant Hodgkin Lymphoma * Prior allogeneic stem cell transplantation (SCT) * Chest radiation ≤ 24 weeks prior to first dose * Carmustine ≥ 600 mg/m² received as part of the pre-transplant conditioning regimen
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Based on IRRC Assessments in Cohorts A, B, and C | From first dose to the date of initial objectively documented progression or the date of subsequent therapy, whichever occurred first (up to approximately 28 months) | ORR is the percent of participants achieving either a complete remission (CR) or partial remission (PR) according to the 2007 IWG criteria. Analyses of efficacy endpoints were performed separately for each cohort, according to IWG 2007. For cohort A and B, if the bone marrow was involved by lymphoma before treatment, the infiltrate must have cleared on repeat bone marrow biopsy. For cohort C, no evidence of FDG-avid disease in bone marrow was required in all participants in lieu of bone marrow aspirate/ biopsy. CR is the percent of participants with a best overall response (BOR) of CR (disappearance of all evidence of disease) according to the 2007 IWG criteria, based on IRRC assessment. PR is the percent of participants with a best overall response (BOR) of PR (regression of measurable disease and no new sites) according to the 2007 IWG criteria, based on IRRC assessment. Confidence interval based on Clopper-Pearson method. |
| Number of Participants Who Experienced at Least One Treatment Related Grade 3-5 AE in Cohort D | From first dose of the considered therapy phase to 30 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 8 months and a maximum of 11 months) | An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation subject administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Remission (CR) Rate Based on IRRC Assessments in Cohorts A, B, and C | From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months) | The CR rate was defined as the percent of participants with a BOR of CR (disappearance of all evidence of disease) according to the 2007 IWG criteria, based on IRRC assessment. Confidence interval based on Clopper-Pearson method. |
| Duration of Complete Remission (CR) Based on IRRC Assessments for Cohorts A, B, and C | From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months) | The duration of CR was only evaluated in participants with BOR of CR and was defined as the time from first documentation of CR (the date of first negative FDG-PET scan or the date of first documentation of no disease involvement in the bone marrow (if required), whichever occurred later) to the date of initial objectively documented progression (Any new lesion or increase by \>=50% of previously involved sites from nadir) as determined using the 2007 IWG criteria or death due to any cause, whichever occurred first. Censoring was applied as per DOR definition. Computed using Kaplan-Meier method. |
| Partial Remission (PR) Rate Based on IRRC Assessments in Cohorts A, B, and C | From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months) | The PR rate was defined as the percent of participants with a BOR of PR (regression of measurable disease and no new sites) according to the 2007 IWG criteria, based on IRRC assessment. Confidence interval based on Clopper-Pearson method. |
| Duration of PR Based on IRRC Assessments in Cohorts A, B, and C | From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months) | The duration of PR was only evaluated in participants with BOR of PR and was defined as the time from first documentation of PR (regression of measurable disease and no new sites) to the date of initial objectively documented progression (any new lesion or increase by \>=50% of previously involved sites from nadir) as determined using the 2007 IWG criteria or death due to any cause, whichever occurred first. Censoring was applied as per DOR definition. Computed using Kaplan-Meier method. |
| Objective Response Rates (ORR) Based on Investigator Assessments for Cohorts A, B, and C | From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months) | ORR is the percent of participants achieving either a complete remission (CR) or partial remission (PR) according to the 2007 IWG criteria. Analyses of efficacy endpoints were performed separately for each cohort, according to IWG 2007. For cohort A and B, if the bone marrow was involved by lymphoma before treatment, the infiltrate must have cleared on repeat bone marrow biopsy. For cohort C, no evidence of FDG-avid disease in bone marrow was required in all participants in lieu of bone marrow aspirate/ biopsy. CR is the percent of participants with a best overall response (BOR) of CR (disappearance of all evidence of disease) according to the 2007 IWG criteria, based on IRRC assessment. PR is the percent of participants with a best overall response (BOR) of PR (regression of measurable disease and no new sites) according to the 2007 IWG criteria, based on IRRC assessment. Confidence interval based on Clopper-Pearson method. |
| Duration of Objective Response (DOR) Based on Investigator Assessments in Cohorts A, B, and C | From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months) | DOR is the time from first response (complete remission (CR) or partial remission (PR)) to the date of initial objectively documented progression as determined using the 2007 IWG criteria or death due to any cause, whichever occurred first. For participants who neither progressed nor died, the DOR was censored on the date of their last tumor assessment. Participants who started subsequent therapy without a prior reported progression were censored at the last tumor assessments prior to initiation of the subsequent anticancer therapy. CR is the percent of participants with a best overall response (BOR) of CR (disappearance of all evidence of disease) according to the 2007 IWG criteria, based on IRRC assessment. PR is the percent of participants with a best overall response (BOR) of PR (regression of measurable disease and no new sites) according to the 2007 IWG criteria, based on IRRC assessment. Computed using Kaplan-Meier method. |
| Treatment Discontinuation Rate in Cohort D | From first dose up until the date of treatment discontinuation (up to approximately 100 months). | Treatment discontinuation rate (TDR) is the number of treated participants who received \<4 doses of monotherapy or \<12 doses of their assigned combination regimen. A participant is considered as having received an AVD/NAVD dose as soon as they received at least one drug of AVD/NAVD for the considered dose. Participants must have received at least one dose of Nivolumab during the combination therapy phase to be included in participants treated with NAVD. If a participant subsequently met Criteria to Resume Nivolumab Dosing, the combination of nivolumab and AVD could be used. Participants who underwent treatment beyond progression during the Monotherapy phase could use the combination of nivolumab and AVD if all 4 doses of nivolumab monotherapy are completed. Discontinuation can be due to any reason including, but not limited to, drug-related toxicity, diseases progression, or death. |
| Number of Participants Who Died in Cohort D | From first dose of the considered therapy phase to 100 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 10 months up to a maximum of 13 months) | Number of participants who died in Cohort D within 100 days after last dose of study therapy. |
| Number of Participants With AEs Leading to Dose Delay in Cohort D | From first dose of the considered therapy phase to 30 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 8 months and a maximum of 11 months) | An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. |
| Number of Participants With Serious Adverse Events (SAEs) in Cohort D | From first dose of the considered therapy phase to 30 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 8 months and a maximum of 11 months) | A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose results in death, is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. |
| Number of Participants With AEs Leading to Discontinuation in Cohort D | From first dose of the considered therapy phase to 30 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 8 months and a maximum of 11 months) | An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. |
| Number of Participants With Select AEs in Cohort D | From first dose of the considered therapy phase to 30 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 8 months and a maximum of 11 months) | An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Select AEs have been categorized into seven areas: pulmonary toxicity, gastrointestinal toxicity, hepatotoxicity, endocrinopathy, skin toxicity, neurological toxicity and renal toxicity. Select AEs, in particular pneumonitis, are considered clinically meaningful as they require greater vigilance and for early recognition and prompt intervention. |
| Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Monotherapy Phase | From first dose of monotherapy to 30 days after last dose of monotherapy phase (up to approximately 3 months) | The number of participants with laboratory abnormalities in specific thyroid tests based on SI conventional units. TSH = Thyroid Stimulating Hormone LLN = Lower Limit of Normal ULN = Upper Limit of Normal |
| Number of Participants Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Combination Therapy Phase | From first dose of the combination therapy to 30 days after last dose of combination therapy (an average of 8 months and a maximum of 11 months) | The number of participants with laboratory abnormalities in specific thyroid tests based on SI conventional units. TSH = Thyroid Stimulating Hormone LLN = Lower Limit of Normal ULN = Upper Limit of Normal |
| Number of Participants With Laboratory Abnormalities in Specific Liver Tests in Cohort D Monotherapy Phase | From first dose of monotherapy to 30 days after last dose of monotherapy phase (up to approximately 3 months) | The number of participants with laboratory abnormalities in specific liver tests based on SI conventional units. ALT = Alanine Aminotransferase, AST = Aspartate Aminotransferase, ULN = Upper Limit of Normal. |
| Number of Participants With Laboratory Abnormalities in Specific Liver Tests in Cohort D Combination Therapy Phase | From first dose of the combination therapy to 30 days after last dose of combination therapy (an average of 8 months and a maximum of 11 months) | The number of participants with laboratory abnormalities in specific liver tests based on SI conventional units. ALT = Alanine Aminotransferase, AST = Aspartate Aminotransferase, ULN = Upper Limit of Normal. |
| Complete Response (CR) Rate at Planned End of Therapy Based on IRRC Assessments in Cohort D | From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months) | CR rate is the percent of participants who show CR (disappearance of all evidence of disease) according to the 2007 IWG criteria at the planned end of study therapy radiographic tumor assessment. Confidence interval based on the Klopper and Pearson method. |
| Number of Participants With Adverse Events (AEs) in Cohort D | From first dose of the considered therapy phase to 30 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 8 months and a maximum of 11 months) | An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. |
| Duration of Objective Response Based on IRRC Assessments in Cohorts A, B, and C | From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months). | DOR is the time from first response (complete remission (CR) or partial remission (PR)) to the date of initial objectively documented progression as determined using the 2007 IWG criteria or death due to any cause, whichever occurred first. For participants who neither progressed nor died, the DOR was censored on the date of their last tumor assessment. Participants who started subsequent therapy without a prior reported progression were censored at the last tumor assessments prior to initiation of the subsequent anticancer therapy. CR is the percent of participants with a best overall response (BOR) of CR (disappearance of all evidence of disease) according to the 2007 IWG criteria, based on IRRC assessment. PR is the percent of participants with a best overall response (BOR) of PR (regression of measurable disease and no new sites) according to the 2007 IWG criteria, based on IRRC assessment. Computed using Kaplan-Meier method. |
Countries
Austria, Belgium, Canada, Czechia, Germany, Italy, Netherlands, Spain, United Kingdom, United States
Participant flow
Recruitment details
243 participants were treated at 34 sites in 10 countries for cohorts A, B, and C. Cohort D enrolled separately. 51 participants were treated in cohort D for a total of 294 participants treated all together.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression. | 63 |
| Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Autologous Stem Cell Transplant Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression. | 80 |
| Cohort C: Post Transplant, Brentuximab Vedotin Taken Pre-and/or Post-Autologous Stem Cell Transplant Nivolumab was administered at 3 mg/kg IV over 60 minutes on the first day of each 2-week cycle. Upon the implementation of revised protocol version 04c (dated 22-Aug-2019), participants were switched from a body weight-based dose of 3 mg/kg every 2 weeks to a flat dose of 480 mg every 4 weeks or a flat dose of 240 mg every 2 weeks. Nivolumab treatment was continued until unacceptable toxicity or disease progression. | 100 |
| Cohort D: Newly Diagnosed, Previously Untreated Advanced Stage cHL (Stage IIB, III and IV) Four doses of nivolumab flat dose 240 mg IV were administered every 2 weeks (monotherapy phase), followed by 12 doses of the combination of AVD (adriamycin/ doxorubicin 25 mg/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2) chemotherapy and nivolumab flat dose 240 mg IV for 6 cycles (combination phase). | 51 |
| Total | 294 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event Unrelated to Study Drug | 3 | 3 | 1 | 0 |
| Overall Study | Disease Progression | 28 | 35 | 40 | 0 |
| Overall Study | Lost to Follow-up | 1 | 2 | 1 | 1 |
| Overall Study | Maximum Clinical Benefit | 3 | 0 | 1 | 0 |
| Overall Study | Other Reasons | 14 | 16 | 28 | 0 |
| Overall Study | Participant no Longer Meets Study Criteria | 0 | 0 | 0 | 1 |
| Overall Study | Participant Request to Discontinue Study Treatment | 5 | 12 | 5 | 1 |
| Overall Study | Participant Withdrew Consent | 2 | 1 | 1 | 1 |
| Overall Study | Poor/Non-Compliance | 1 | 0 | 2 | 1 |
| Overall Study | Study Drug Toxicity | 6 | 11 | 8 | 1 |
Baseline characteristics
| Characteristic | Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Autologous Stem Cell Transplant | Cohort C: Post Transplant, Brentuximab Vedotin Taken Pre-and/or Post-Autologous Stem Cell Transplant | Cohort D: Newly Diagnosed, Previously Untreated Advanced Stage cHL (Stage IIB, III and IV) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 36.3 Years STANDARD_DEVIATION 12.54 | 38.7 Years STANDARD_DEVIATION 13 | 36.1 Years STANDARD_DEVIATION 12.41 | 39.0 Years STANDARD_DEVIATION 16.88 | 37.4 Years STANDARD_DEVIATION 13.47 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 63 Participants | 56 Participants | 40 Participants | 189 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 30 Participants | 16 Participants | 43 Participants | 11 Participants | 100 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 1 Participants | 5 Participants | 2 Participants | 11 Participants |
| Race/Ethnicity, Customized Black or African | 2 Participants | 4 Participants | 6 Participants | 2 Participants | 14 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 4 Participants | 1 Participants | 2 Participants | 11 Participants |
| Race/Ethnicity, Customized White | 54 Participants | 71 Participants | 86 Participants | 45 Participants | 256 Participants |
| Sex: Female, Male Female | 29 Participants | 29 Participants | 44 Participants | 19 Participants | 121 Participants |
| Sex: Female, Male Male | 34 Participants | 51 Participants | 56 Participants | 32 Participants | 173 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 14 / 46 | 3 / 9 | 0 / 8 | 25 / 75 | 0 / 3 | 0 / 2 | 31 / 84 | 4 / 13 | 0 / 3 | 5 / 51 |
| other Total, other adverse events | 46 / 46 | 9 / 9 | 8 / 8 | 75 / 75 | 3 / 3 | 2 / 2 | 80 / 84 | 13 / 13 | 3 / 3 | 50 / 51 |
| serious Total, serious adverse events | 10 / 46 | 3 / 9 | 1 / 8 | 30 / 75 | 0 / 3 | 1 / 2 | 33 / 84 | 8 / 13 | 3 / 3 | 12 / 51 |
Outcome results
Primary
Number of Participants Who Experienced at Least One Treatment Related Grade 3-5 AE in Cohort D
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation subject administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug.
Time frame: From first dose of the considered therapy phase to 30 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 8 months and a maximum of 11 months)
Population: All Cohort D participants treated in the monotherapy and combination therapy phases.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants Who Experienced at Least One Treatment Related Grade 3-5 AE in Cohort D | Combination Therapy (receiving AVD or NAVD) | 30 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants Who Experienced at Least One Treatment Related Grade 3-5 AE in Cohort D | Monotherapy | 0 Participants |
Primary
Objective Response Rate (ORR) Based on IRRC Assessments in Cohorts A, B, and C
ORR is the percent of participants achieving either a complete remission (CR) or partial remission (PR) according to the 2007 IWG criteria. Analyses of efficacy endpoints were performed separately for each cohort, according to IWG 2007. For cohort A and B, if the bone marrow was involved by lymphoma before treatment, the infiltrate must have cleared on repeat bone marrow biopsy. For cohort C, no evidence of FDG-avid disease in bone marrow was required in all participants in lieu of bone marrow aspirate/ biopsy. CR is the percent of participants with a best overall response (BOR) of CR (disappearance of all evidence of disease) according to the 2007 IWG criteria, based on IRRC assessment. PR is the percent of participants with a best overall response (BOR) of PR (regression of measurable disease and no new sites) according to the 2007 IWG criteria, based on IRRC assessment. Confidence interval based on Clopper-Pearson method.
Time frame: From first dose to the date of initial objectively documented progression or the date of subsequent therapy, whichever occurred first (up to approximately 28 months)
Population: All treated Cohort A, B and C participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Objective Response Rate (ORR) Based on IRRC Assessments in Cohorts A, B, and C | 65.1 Percentage of Particpants |
| Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Autologous Stem Cell Transplant | Objective Response Rate (ORR) Based on IRRC Assessments in Cohorts A, B, and C | 67.5 Percentage of Particpants |
| Cohort C: Post Transplant, Brentuximab Vedotin Taken Pre-and/or Post-Autologous Stem Cell Transplant | Objective Response Rate (ORR) Based on IRRC Assessments in Cohorts A, B, and C | 73.0 Percentage of Particpants |
Secondary
Complete Remission (CR) Rate Based on IRRC Assessments in Cohorts A, B, and C
The CR rate was defined as the percent of participants with a BOR of CR (disappearance of all evidence of disease) according to the 2007 IWG criteria, based on IRRC assessment. Confidence interval based on Clopper-Pearson method.
Time frame: From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months)
Population: All treated Cohort A, B and C participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Complete Remission (CR) Rate Based on IRRC Assessments in Cohorts A, B, and C | 31.7 Percentage of Participants |
| Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Autologous Stem Cell Transplant | Complete Remission (CR) Rate Based on IRRC Assessments in Cohorts A, B, and C | 13.8 Percentage of Participants |
| Cohort C: Post Transplant, Brentuximab Vedotin Taken Pre-and/or Post-Autologous Stem Cell Transplant | Complete Remission (CR) Rate Based on IRRC Assessments in Cohorts A, B, and C | 21 Percentage of Participants |
Secondary
Complete Response (CR) Rate at Planned End of Therapy Based on IRRC Assessments in Cohort D
CR rate is the percent of participants who show CR (disappearance of all evidence of disease) according to the 2007 IWG criteria at the planned end of study therapy radiographic tumor assessment. Confidence interval based on the Klopper and Pearson method.
Time frame: From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months)
Population: All Cohort D participants treated in the monotherapy and combination therapy phases.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Complete Response (CR) Rate at Planned End of Therapy Based on IRRC Assessments in Cohort D | 66.7 Percent of Participants |
Secondary
Duration of Complete Remission (CR) Based on IRRC Assessments for Cohorts A, B, and C
The duration of CR was only evaluated in participants with BOR of CR and was defined as the time from first documentation of CR (the date of first negative FDG-PET scan or the date of first documentation of no disease involvement in the bone marrow (if required), whichever occurred later) to the date of initial objectively documented progression (Any new lesion or increase by \>=50% of previously involved sites from nadir) as determined using the 2007 IWG criteria or death due to any cause, whichever occurred first. Censoring was applied as per DOR definition. Computed using Kaplan-Meier method.
Time frame: From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months)
Population: All treated Cohort A, B and C participants who had a BOR of CR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Duration of Complete Remission (CR) Based on IRRC Assessments for Cohorts A, B, and C | 43.47 Months |
| Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Autologous Stem Cell Transplant | Duration of Complete Remission (CR) Based on IRRC Assessments for Cohorts A, B, and C | 30.32 Months |
| Cohort C: Post Transplant, Brentuximab Vedotin Taken Pre-and/or Post-Autologous Stem Cell Transplant | Duration of Complete Remission (CR) Based on IRRC Assessments for Cohorts A, B, and C | 26.41 Months |
Secondary
Duration of Objective Response Based on IRRC Assessments in Cohorts A, B, and C
DOR is the time from first response (complete remission (CR) or partial remission (PR)) to the date of initial objectively documented progression as determined using the 2007 IWG criteria or death due to any cause, whichever occurred first. For participants who neither progressed nor died, the DOR was censored on the date of their last tumor assessment. Participants who started subsequent therapy without a prior reported progression were censored at the last tumor assessments prior to initiation of the subsequent anticancer therapy. CR is the percent of participants with a best overall response (BOR) of CR (disappearance of all evidence of disease) according to the 2007 IWG criteria, based on IRRC assessment. PR is the percent of participants with a best overall response (BOR) of PR (regression of measurable disease and no new sites) according to the 2007 IWG criteria, based on IRRC assessment. Computed using Kaplan-Meier method.
Time frame: From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months).
Population: All treated Cohort A, B and C participants with objective response of CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Duration of Objective Response Based on IRRC Assessments in Cohorts A, B, and C | 26.18 Months |
| Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Autologous Stem Cell Transplant | Duration of Objective Response Based on IRRC Assessments in Cohorts A, B, and C | 16.59 Months |
| Cohort C: Post Transplant, Brentuximab Vedotin Taken Pre-and/or Post-Autologous Stem Cell Transplant | Duration of Objective Response Based on IRRC Assessments in Cohorts A, B, and C | 18.17 Months |
Secondary
Duration of Objective Response (DOR) Based on Investigator Assessments in Cohorts A, B, and C
DOR is the time from first response (complete remission (CR) or partial remission (PR)) to the date of initial objectively documented progression as determined using the 2007 IWG criteria or death due to any cause, whichever occurred first. For participants who neither progressed nor died, the DOR was censored on the date of their last tumor assessment. Participants who started subsequent therapy without a prior reported progression were censored at the last tumor assessments prior to initiation of the subsequent anticancer therapy. CR is the percent of participants with a best overall response (BOR) of CR (disappearance of all evidence of disease) according to the 2007 IWG criteria, based on IRRC assessment. PR is the percent of participants with a best overall response (BOR) of PR (regression of measurable disease and no new sites) according to the 2007 IWG criteria, based on IRRC assessment. Computed using Kaplan-Meier method.
Time frame: From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months)
Population: All treated Cohort A, B and C participants who had a BOR of CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Duration of Objective Response (DOR) Based on Investigator Assessments in Cohorts A, B, and C | 39.10 Months |
| Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Autologous Stem Cell Transplant | Duration of Objective Response (DOR) Based on Investigator Assessments in Cohorts A, B, and C | 25.26 Months |
| Cohort C: Post Transplant, Brentuximab Vedotin Taken Pre-and/or Post-Autologous Stem Cell Transplant | Duration of Objective Response (DOR) Based on Investigator Assessments in Cohorts A, B, and C | 28.85 Months |
Secondary
Duration of PR Based on IRRC Assessments in Cohorts A, B, and C
The duration of PR was only evaluated in participants with BOR of PR and was defined as the time from first documentation of PR (regression of measurable disease and no new sites) to the date of initial objectively documented progression (any new lesion or increase by \>=50% of previously involved sites from nadir) as determined using the 2007 IWG criteria or death due to any cause, whichever occurred first. Censoring was applied as per DOR definition. Computed using Kaplan-Meier method.
Time frame: From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months)
Population: All treated Cohort A, B and C participants who had a BOR of PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Duration of PR Based on IRRC Assessments in Cohorts A, B, and C | 12.78 Months |
| Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Autologous Stem Cell Transplant | Duration of PR Based on IRRC Assessments in Cohorts A, B, and C | 10.58 Months |
| Cohort C: Post Transplant, Brentuximab Vedotin Taken Pre-and/or Post-Autologous Stem Cell Transplant | Duration of PR Based on IRRC Assessments in Cohorts A, B, and C | 14.65 Months |
Secondary
Number of Participants Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Combination Therapy Phase
The number of participants with laboratory abnormalities in specific thyroid tests based on SI conventional units. TSH = Thyroid Stimulating Hormone LLN = Lower Limit of Normal ULN = Upper Limit of Normal
Time frame: From first dose of the combination therapy to 30 days after last dose of combination therapy (an average of 8 months and a maximum of 11 months)
Population: All participants treated in the Cohort D combination therapy phase who had at least one on-treatment AST, ALT and/or bilirubin test measurement during the combination therapy phase
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Combination Therapy Phase | TSH > ULN | 12 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Combination Therapy Phase | TSH > ULN WITH TSH <= ULN AT BASELINE | 8 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Combination Therapy Phase | TSH >ULN WITH ATLEAST ONE FT3/FT4 TEST VALUE <LLN | 3 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Combination Therapy Phase | TSH >ULN WITH ALL OTHER FT3/FT4 TEST VALUES >= LLN | 1 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Combination Therapy Phase | TSH > ULN WITH FT3/FT4 TEST MISSING | 8 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Combination Therapy Phase | TSH < LLN | 5 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Combination Therapy Phase | TSH <LLN WITH TSH >= LLN AT BASELINE | 5 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Combination Therapy Phase | TSH <LLN WITH ATLEAST ONE FT3/FT4 TEST VALUE > ULN | 1 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Combination Therapy Phase | TSH <LLN WITH ALL OTHER FT3/FT4 TEST VALUES <= ULN | 0 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Combination Therapy Phase | TSH < LLN WITH FT3/FT4 TEST MISSING | 4 Participants |
Secondary
Number of Participants Who Died in Cohort D
Number of participants who died in Cohort D within 100 days after last dose of study therapy.
Time frame: From first dose of the considered therapy phase to 100 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 10 months up to a maximum of 13 months)
Population: All Cohort D participants treated in the monotherapy and combination therapy phases.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants Who Died in Cohort D | Monotherapy | 0 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants Who Died in Cohort D | Combination Therapy (receiving AVD or NAVD) | 1 Participants |
Secondary
Number of Participants With Adverse Events (AEs) in Cohort D
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Time frame: From first dose of the considered therapy phase to 30 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 8 months and a maximum of 11 months)
Population: All treated participants in Cohort D
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Adverse Events (AEs) in Cohort D | Monotherapy | 48 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Adverse Events (AEs) in Cohort D | Combination Therapy (receiving AVD or NAVD) | 49 Participants |
Secondary
Number of Participants With AEs Leading to Discontinuation in Cohort D
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Time frame: From first dose of the considered therapy phase to 30 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 8 months and a maximum of 11 months)
Population: All treated participants in Cohort D
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With AEs Leading to Discontinuation in Cohort D | Monotherapy | 1 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With AEs Leading to Discontinuation in Cohort D | Combination Therapy (receiving AVD or NAVD) | 3 Participants |
Secondary
Number of Participants With AEs Leading to Dose Delay in Cohort D
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Time frame: From first dose of the considered therapy phase to 30 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 8 months and a maximum of 11 months)
Population: All treated participants in Cohort D
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With AEs Leading to Dose Delay in Cohort D | Monotherapy | 3 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With AEs Leading to Dose Delay in Cohort D | Combination Therapy (receiving AVD or NAVD) | 29 Participants |
Secondary
Number of Participants With Laboratory Abnormalities in Specific Liver Tests in Cohort D Combination Therapy Phase
The number of participants with laboratory abnormalities in specific liver tests based on SI conventional units. ALT = Alanine Aminotransferase, AST = Aspartate Aminotransferase, ULN = Upper Limit of Normal.
Time frame: From first dose of the combination therapy to 30 days after last dose of combination therapy (an average of 8 months and a maximum of 11 months)
Population: All participants treated in the Cohort D combination therapy phase with at least one on-treatment laboratory measurement
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Laboratory Abnormalities in Specific Liver Tests in Cohort D Combination Therapy Phase | ALT OR AST > 20XULN | 0 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Laboratory Abnormalities in Specific Liver Tests in Cohort D Combination Therapy Phase | ALT OR AST > 3XULN | 4 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Laboratory Abnormalities in Specific Liver Tests in Cohort D Combination Therapy Phase | ALT OR AST> 5XULN | 1 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Laboratory Abnormalities in Specific Liver Tests in Cohort D Combination Therapy Phase | ALT OR AST> 10XULN | 1 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Laboratory Abnormalities in Specific Liver Tests in Cohort D Combination Therapy Phase | TOTAL BILIRUBIN > 2XULN | 0 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Laboratory Abnormalities in Specific Liver Tests in Cohort D Combination Therapy Phase | ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 1 DAY | 0 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Laboratory Abnormalities in Specific Liver Tests in Cohort D Combination Therapy Phase | ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 30 DAYS | 0 Participants |
Secondary
Number of Participants With Laboratory Abnormalities in Specific Liver Tests in Cohort D Monotherapy Phase
The number of participants with laboratory abnormalities in specific liver tests based on SI conventional units. ALT = Alanine Aminotransferase, AST = Aspartate Aminotransferase, ULN = Upper Limit of Normal.
Time frame: From first dose of monotherapy to 30 days after last dose of monotherapy phase (up to approximately 3 months)
Population: All participants treated in the Cohort D monotherapy phase
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Laboratory Abnormalities in Specific Liver Tests in Cohort D Monotherapy Phase | ALT OR AST > 3XULN | 2 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Laboratory Abnormalities in Specific Liver Tests in Cohort D Monotherapy Phase | ALT OR AST> 5XULN | 1 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Laboratory Abnormalities in Specific Liver Tests in Cohort D Monotherapy Phase | ALT OR AST> 10XULN | 0 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Laboratory Abnormalities in Specific Liver Tests in Cohort D Monotherapy Phase | ALT OR AST > 20XULN | 0 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Laboratory Abnormalities in Specific Liver Tests in Cohort D Monotherapy Phase | TOTAL BILIRUBIN > 2XULN | 0 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Laboratory Abnormalities in Specific Liver Tests in Cohort D Monotherapy Phase | ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 1 DAY | 0 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Laboratory Abnormalities in Specific Liver Tests in Cohort D Monotherapy Phase | ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 30 DAYS | 0 Participants |
Secondary
Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Monotherapy Phase
The number of participants with laboratory abnormalities in specific thyroid tests based on SI conventional units. TSH = Thyroid Stimulating Hormone LLN = Lower Limit of Normal ULN = Upper Limit of Normal
Time frame: From first dose of monotherapy to 30 days after last dose of monotherapy phase (up to approximately 3 months)
Population: All participants treated in the Cohort D monotherapy phase who had at least one on-treatment TSH measurement during the monotherapy phase
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Monotherapy Phase | TSH < LLN | 5 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Monotherapy Phase | TSH <LLN WITH TSH >= LLN AT BASELINE | 5 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Monotherapy Phase | TSH > ULN | 1 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Monotherapy Phase | TSH > ULN WITH TSH <= ULN AT BASELINE | 1 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Monotherapy Phase | TSH >ULN WITH ATLEAST ONE FT3/FT4 TEST VALUE <LLN | 0 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Monotherapy Phase | TSH >ULN WITH ALL OTHER FT3/FT4 TEST VALUES >= LLN | 0 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Monotherapy Phase | TSH > ULN WITH FT3/FT4 TEST MISSING | 1 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Monotherapy Phase | TSH <LLN WITH ATLEAST ONE FT3/FT4 TEST VALUE > ULN | 1 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Monotherapy Phase | TSH <LLN WITH ALL OTHER FT3/FT4 TEST VALUES <= ULN | 0 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests in Cohort D Monotherapy Phase | TSH < LLN WITH FT3/FT4 TEST MISSING | 4 Participants |
Secondary
Number of Participants With Select AEs in Cohort D
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Select AEs have been categorized into seven areas: pulmonary toxicity, gastrointestinal toxicity, hepatotoxicity, endocrinopathy, skin toxicity, neurological toxicity and renal toxicity. Select AEs, in particular pneumonitis, are considered clinically meaningful as they require greater vigilance and for early recognition and prompt intervention.
Time frame: From first dose of the considered therapy phase to 30 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 8 months and a maximum of 11 months)
Population: All treated participants in Cohort D
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Select AEs in Cohort D | Pulmonary Monotherapy | 0 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Select AEs in Cohort D | Gastrointestinal Monotherapy | 6 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Select AEs in Cohort D | Gastrointestinal Combination Therapy | 13 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Select AEs in Cohort D | Hepatic Monotherapy | 2 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Select AEs in Cohort D | Hepatic Combination Therapy | 3 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Select AEs in Cohort D | Pulmonary Combination Therapy | 3 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Select AEs in Cohort D | Renal Monotherapy | 1 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Select AEs in Cohort D | Renal Combination Therapy | 0 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Select AEs in Cohort D | Skin Monotherapy | 17 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Select AEs in Cohort D | Skin Combination Therapy | 9 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Select AEs in Cohort D | Hypersensitivity/Infusion Reactions Monotherapy | 16 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Select AEs in Cohort D | Hypersensitivity/Infusion Reactions Combination | 4 Participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs) in Cohort D
A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose results in death, is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Time frame: From first dose of the considered therapy phase to 30 days after last dose of study therapy phase (or up to first dose of combination if any when considering the monotherapy period) (an average of 8 months and a maximum of 11 months)
Population: All treated participants in Cohort D
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Serious Adverse Events (SAEs) in Cohort D | Monotherapy | 2 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Number of Participants With Serious Adverse Events (SAEs) in Cohort D | Combination Therapy (receiving AVD or NAVD) | 10 Participants |
Secondary
Objective Response Rates (ORR) Based on Investigator Assessments for Cohorts A, B, and C
ORR is the percent of participants achieving either a complete remission (CR) or partial remission (PR) according to the 2007 IWG criteria. Analyses of efficacy endpoints were performed separately for each cohort, according to IWG 2007. For cohort A and B, if the bone marrow was involved by lymphoma before treatment, the infiltrate must have cleared on repeat bone marrow biopsy. For cohort C, no evidence of FDG-avid disease in bone marrow was required in all participants in lieu of bone marrow aspirate/ biopsy. CR is the percent of participants with a best overall response (BOR) of CR (disappearance of all evidence of disease) according to the 2007 IWG criteria, based on IRRC assessment. PR is the percent of participants with a best overall response (BOR) of PR (regression of measurable disease and no new sites) according to the 2007 IWG criteria, based on IRRC assessment. Confidence interval based on Clopper-Pearson method.
Time frame: From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months)
Population: All treated Cohort A, B and C participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Objective Response Rates (ORR) Based on Investigator Assessments for Cohorts A, B, and C | 69.8 Percentage of Participants |
| Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Autologous Stem Cell Transplant | Objective Response Rates (ORR) Based on Investigator Assessments for Cohorts A, B, and C | 73.8 Percentage of Participants |
| Cohort C: Post Transplant, Brentuximab Vedotin Taken Pre-and/or Post-Autologous Stem Cell Transplant | Objective Response Rates (ORR) Based on Investigator Assessments for Cohorts A, B, and C | 70.0 Percentage of Participants |
Secondary
Partial Remission (PR) Rate Based on IRRC Assessments in Cohorts A, B, and C
The PR rate was defined as the percent of participants with a BOR of PR (regression of measurable disease and no new sites) according to the 2007 IWG criteria, based on IRRC assessment. Confidence interval based on Clopper-Pearson method.
Time frame: From first dose to the date of initial objectively documented progression or the date of subsequent therapy, or death whichever occurred first (up to approximately 100 months)
Population: All treated Cohort A, B and C participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Partial Remission (PR) Rate Based on IRRC Assessments in Cohorts A, B, and C | 33.3 Percentage of Participants |
| Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Autologous Stem Cell Transplant | Partial Remission (PR) Rate Based on IRRC Assessments in Cohorts A, B, and C | 57.5 Percentage of Participants |
| Cohort C: Post Transplant, Brentuximab Vedotin Taken Pre-and/or Post-Autologous Stem Cell Transplant | Partial Remission (PR) Rate Based on IRRC Assessments in Cohorts A, B, and C | 54.0 Percentage of Participants |
Secondary
Treatment Discontinuation Rate in Cohort D
Treatment discontinuation rate (TDR) is the number of treated participants who received \<4 doses of monotherapy or \<12 doses of their assigned combination regimen. A participant is considered as having received an AVD/NAVD dose as soon as they received at least one drug of AVD/NAVD for the considered dose. Participants must have received at least one dose of Nivolumab during the combination therapy phase to be included in participants treated with NAVD. If a participant subsequently met Criteria to Resume Nivolumab Dosing, the combination of nivolumab and AVD could be used. Participants who underwent treatment beyond progression during the Monotherapy phase could use the combination of nivolumab and AVD if all 4 doses of nivolumab monotherapy are completed. Discontinuation can be due to any reason including, but not limited to, drug-related toxicity, diseases progression, or death.
Time frame: From first dose up until the date of treatment discontinuation (up to approximately 100 months).
Population: All Cohort D participants treated in the monotherapy and combination therapy phases.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Treatment Discontinuation Rate in Cohort D | Monotherapy | 2 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Treatment Discontinuation Rate in Cohort D | Combination Therapy (receiving AVD or NAVD) | 5 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Treatment Discontinuation Rate in Cohort D | Combination Therapy (NAVD receivers only) | 5 Participants |
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Treatment Discontinuation Rate in Cohort D | Overall Therapy | 6 Participants |
Post Hoc
Objective Response Rate (ORR) Based on IRRC Assessments in Cohorts A, B, and C Extended Collection
Represents an updated version of the primary endpoint to include additional data collection that occurred after the primary completion date. (Assessments were made until 30 Nov 2022). Clinical benefit of nivolumab, as measured by ORR per IRRC assessment, and defined as percent of participants achieving either complete remission (CR) or partial remission (PR) according to the 2007 IWG criteria. For cohort A and B, if the bone marrow was involved by lymphoma before treatment, the infiltrate must have cleared on repeat bone marrow biopsy. For cohort C, no evidence of FDG-avid disease in bone marrow was required in all patients in lieu of bone marrow aspirate/ biopsy. CR is the percent of participants with a best overall response (BOR) of CR (disappearance of all evidence of disease) according to the 2007 IWG criteria. PR is the percent of participants with a best overall response (BOR) of PR (regression of measurable disease and no new sites) according to the 2007 IWG criteria.
Time frame: From first dose to the date of initial objectively documented progression or the date of subsequent therapy, whichever occurred first (up to approximately 100 months)
Population: All treated Cohort A, B and C participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Post-Transplant, Never Taken Brentuximab Vedotin | Objective Response Rate (ORR) Based on IRRC Assessments in Cohorts A, B, and C Extended Collection | 65.1 Percentage of Participants |
| Cohort B: Post Transplant, Brentuximab Vedotin Taken Post-Autologous Stem Cell Transplant | Objective Response Rate (ORR) Based on IRRC Assessments in Cohorts A, B, and C Extended Collection | 71.3 Percentage of Participants |
| Cohort C: Post Transplant, Brentuximab Vedotin Taken Pre-and/or Post-Autologous Stem Cell Transplant | Objective Response Rate (ORR) Based on IRRC Assessments in Cohorts A, B, and C Extended Collection | 75.0 Percentage of Participants |