Lymphoma. Non-Hodgkin
Conditions
Brief summary
The purpose of this study is to determine whether Nivolumab is effective in the treatment of DLBCL in patients that have failed or are ineligible for ASCT
Interventions
DRUGNivolumab
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
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Confirmation of relapsed or refractory DLBCL or transformed lymphoma (TL) * Eastern Cooperative Oncology Group (ECOG) performance status of 0 -1 * At least one lesion that measures \>1.5 cm * Prior therapy and screening lab criteria must be met * Appropriate contraceptive measures must be taken
Exclusion criteria
* Known central nervous system (CNS) lymphoma * History of interstitial lung disease, prior malignancy, active autoimmune disease, positive test for hepatitis B or hepatitis C virus * Prior allogeneic stem cell transplant (SCT), chest radiation ≤ 24 weeks from study drug, ≥1000 mg of Carmustine Bis-chloroethylnitrosourea (BCNU) as part of pre-transplant conditioning regimen, prior treatment with drug targeting T-cell costimulation or immune checkpoint pathways * Women who are breastfeeding or pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Per Independent Radiologic Review Committee (IRRC) Assessment | From first dose until date of documented disease progression or subsequent therapy, whichever occurs first (assesed up to April 2016, approximately 25 months) | ORR is defined as the percentage of participants with a Best Overall Response (BOR) of Complete Remission (CR) or Partial Remission (PR), according to the 2007 revised International Working Group (IWG) Criteria for Malignant Lymphoma, , based on IRRC assessment. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measurable disease and no emergence of new sites |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Remission Rate | From date of first dose to study completion (up to approximately 78 months) | Complete Remission Rate is defined as the percentage of participants with a Best Overall Response (BOR) of Complete Response (CR) according to the 2007 revised IWG Criteria for Malignant Lymphoma, based on Independent Radiology Review Committee (IRRC) assessment. CR= Disappearance of all evidence of disease, confirmed by PET scan. |
| Duration of Complete Remission | From time of first documentation of CR to the date of initial documented disease progression or death due to any cause, whichever occurs first (up approximately 14 months) | The duration of Complete Remission is defined as the time from first documentation of Complete Response (CR) (which is 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 occurs later) to the date of initial objectively documented progression as determined using the 2007 IWG criteria, based on Independent Radiology Review Committee (IRRC) assessment, or death due to any cause, whichever occurs first. CR= Disappearance of all evidence of disease, confirmed by PET scan. |
| Partial Remission Rate | From date of first dose to study completion (up to approximately 78 months) | Partial Remission rate is defined as the percentage of participants with a Best Overall Response (BOR) of Partial Response (PR) according to the 2007 revised IWG Criteria for Malignant Lymphoma, based on Independent Radiology Review Committee (IRRC) assessment. PR= Regression of measurable disease and no emergence of new sites. |
| Duration of Response (DOR) | From date of first response to the date of documented disease progression or death, whichever occurs first (up to approximately 18 months) | DOR is defined as the time from first response (Complete Response (CR) or Partial Response (PR)) to the date of initial objectively documented progression as determined using the 2007 revised IWG Criteria for Malignant Lymphoma, based on Independent Radiology Review Committee (IRRC) assessment, or death due to any cause, whichever occurs first. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measurable disease and no emergence of new sites. |
| Progression Free Survival | From date of first dose to date of documented disease progression or death due to any cause, whichever occurs first (up to approximately 2 months) | Progression Free Survival (PFS) is defined as the time from first dosing date to the date of the first documented progression, as determined by an Independent Radiology Review Committee (IRRC) according to the 2007 revised IWG Criteria for Malignant Lymphoma, or death due to any cause, whichever occurs first. |
| Objective Response Rate (ORR) Per Investigator Assessment | From first dose until date of documented disease progression or subsequent therapy, whichever occurs first (up to approximately 30 months) | ORR is defined as the percentage of participants with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR), according to investigator assessment. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measurable disease and no emergence of new sites. |
| Duration of Partial Remission | From date of first documentation of PR to date of disease progression or death due to any cause, whichever occurs first (up to approximately 12 months) | Duration of Partial Remission is defined as the time from first documentation of Partial Response (PR) to the date of initial objectively documented progression as determined using the 2007 IWG criteria, based on Independent Radiology Review Committee (IRRC) assessment, or death due to any cause, whichever occurs first. PR= Regression of measurable disease and no emergence of new sites. |
Countries
Australia, Belgium, Canada, France, Germany, Italy, Netherlands, Singapore, Spain, Sweden, United Kingdom, United States
Participant flow
Pre-assignment details
121 participants entered the treatment period.
Participants by arm
| Arm | Count |
|---|---|
| ASCT-failed Participants who failed Autologous stem cell transplant (ASCT), treated with Nivolumab 3 mg/Kg Q2W | 87 |
| ASCT-ineligible Participants who were ineligible for Autologous stem cell transplant (ASCT), treated with Nivolumab 3 mg/Kg Q2W | 34 |
| Total | 121 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse event unrelated to study drug | 6 |
| Overall Study | Disease progression | 104 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Other reasons | 2 |
| Overall Study | Participant request to discontinue treatment | 2 |
| Overall Study | Study drug toxicity | 6 |
Baseline characteristics
| Characteristic | ASCT-ineligible | Total | ASCT-failed |
|---|---|---|---|
| Age, Continuous | 66.4 years STANDARD_DEVIATION 12.98 | 61.1 years STANDARD_DEVIATION 11.96 | 59.1 years STANDARD_DEVIATION 10.94 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 64 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 13 Participants | 54 Participants | 41 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 12 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 31 Participants | 102 Participants | 71 Participants |
| Sex: Female, Male Female | 13 Participants | 44 Participants | 31 Participants |
| Sex: Female, Male Male | 21 Participants | 77 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 98 / 121 |
| other Total, other adverse events | 109 / 121 |
| serious Total, serious adverse events | 83 / 121 |
Outcome results
Primary
Objective Response Rate (ORR) Per Independent Radiologic Review Committee (IRRC) Assessment
ORR is defined as the percentage of participants with a Best Overall Response (BOR) of Complete Remission (CR) or Partial Remission (PR), according to the 2007 revised International Working Group (IWG) Criteria for Malignant Lymphoma, , based on IRRC assessment. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measurable disease and no emergence of new sites
Time frame: From first dose until date of documented disease progression or subsequent therapy, whichever occurs first (assesed up to April 2016, approximately 25 months)
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ASCT-failed | Objective Response Rate (ORR) Per Independent Radiologic Review Committee (IRRC) Assessment | 10.3 Percent of participants |
| ASCT-ineligible | Objective Response Rate (ORR) Per Independent Radiologic Review Committee (IRRC) Assessment | 2.9 Percent of participants |
Secondary
Complete Remission Rate
Complete Remission Rate is defined as the percentage of participants with a Best Overall Response (BOR) of Complete Response (CR) according to the 2007 revised IWG Criteria for Malignant Lymphoma, based on Independent Radiology Review Committee (IRRC) assessment. CR= Disappearance of all evidence of disease, confirmed by PET scan.
Time frame: From date of first dose to study completion (up to approximately 78 months)
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ASCT-failed | Complete Remission Rate | 3.4 Percent of participants |
| ASCT-ineligible | Complete Remission Rate | 0 Percent of participants |
Secondary
Duration of Complete Remission
The duration of Complete Remission is defined as the time from first documentation of Complete Response (CR) (which is 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 occurs later) to the date of initial objectively documented progression as determined using the 2007 IWG criteria, based on Independent Radiology Review Committee (IRRC) assessment, or death due to any cause, whichever occurs first. CR= Disappearance of all evidence of disease, confirmed by PET scan.
Time frame: From time of first documentation of CR to the date of initial documented disease progression or death due to any cause, whichever occurs first (up approximately 14 months)
Population: All participants with CR
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ASCT-failed | Duration of Complete Remission | NA Months |
Secondary
Duration of Partial Remission
Duration of Partial Remission is defined as the time from first documentation of Partial Response (PR) to the date of initial objectively documented progression as determined using the 2007 IWG criteria, based on Independent Radiology Review Committee (IRRC) assessment, or death due to any cause, whichever occurs first. PR= Regression of measurable disease and no emergence of new sites.
Time frame: From date of first documentation of PR to date of disease progression or death due to any cause, whichever occurs first (up to approximately 12 months)
Population: All participants with PR
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ASCT-failed | Duration of Partial Remission | 6.64 Months |
| ASCT-ineligible | Duration of Partial Remission | 8.34 Months |
Secondary
Duration of Response (DOR)
DOR is defined as the time from first response (Complete Response (CR) or Partial Response (PR)) to the date of initial objectively documented progression as determined using the 2007 revised IWG Criteria for Malignant Lymphoma, based on Independent Radiology Review Committee (IRRC) assessment, or death due to any cause, whichever occurs first. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measurable disease and no emergence of new sites.
Time frame: From date of first response to the date of documented disease progression or death, whichever occurs first (up to approximately 18 months)
Population: All participants with CR or PR
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ASCT-failed | Duration of Response (DOR) | 11.43 Months |
| ASCT-ineligible | Duration of Response (DOR) | 8.34 Months |
Secondary
Objective Response Rate (ORR) Per Investigator Assessment
ORR is defined as the percentage of participants with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR), according to investigator assessment. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measurable disease and no emergence of new sites.
Time frame: From first dose until date of documented disease progression or subsequent therapy, whichever occurs first (up to approximately 30 months)
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ASCT-failed | Objective Response Rate (ORR) Per Investigator Assessment | 19.5 Percent of participants |
| ASCT-ineligible | Objective Response Rate (ORR) Per Investigator Assessment | 2.9 Percent of participants |
Secondary
Partial Remission Rate
Partial Remission rate is defined as the percentage of participants with a Best Overall Response (BOR) of Partial Response (PR) according to the 2007 revised IWG Criteria for Malignant Lymphoma, based on Independent Radiology Review Committee (IRRC) assessment. PR= Regression of measurable disease and no emergence of new sites.
Time frame: From date of first dose to study completion (up to approximately 78 months)
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ASCT-failed | Partial Remission Rate | 6.9 Percent of participants |
| ASCT-ineligible | Partial Remission Rate | 2.9 Percent of participants |
Secondary
Progression Free Survival
Progression Free Survival (PFS) is defined as the time from first dosing date to the date of the first documented progression, as determined by an Independent Radiology Review Committee (IRRC) according to the 2007 revised IWG Criteria for Malignant Lymphoma, or death due to any cause, whichever occurs first.
Time frame: From date of first dose to date of documented disease progression or death due to any cause, whichever occurs first (up to approximately 2 months)
Population: All treated participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ASCT-failed | Progression Free Survival | 1.87 Months |
| ASCT-ineligible | Progression Free Survival | 1.41 Months |