Lymphoma
Conditions
Brief summary
The purpose of this study is to assess the clinical benefit of Nivolumab, as measured by independent radiologic review committee (IRRC)-assessed objective response rate (ORR) in subjects with FL lymphoma who have failed therapy with both CD20 antibody and an alkylating agent.
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: * Grade 1, 2, or 3a FL without pathologic evidence of transformation * Male and female, ages 18 and above, with relapsed or refractory FL lymphoma after \> or =2 prior treatment lines; each of the 2 prior treatment lines must include at least CD20 antibody and/or an alkylating agent * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1
Exclusion criteria
* Known central nervous system lymphoma * History of interstitial lung disease * Subjects with active, known or suspected autoimmune disease * Prior allogeneic stem cell transplant * Prior autologous stem cell transplant ≤12 weeks prior to first dose of study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) as Determined by IRRC | From Week 9 until documented disease progression or study discontinuation (assessed up to June 2017, approximately 38 months) | ORR is determined by an independent radiologic review committee (IRRC) according to the revised International Working Group Criteria for non-Hodgkin Lymphoma. ORR is defined as the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) and expressed as a percentage of all treated participants. CR=Disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of spleen, liver, and bone marrow involvement. PR=Regression of measurable disease and no new sites; no increase in size of liver or spleen. \>=50% decrease in SPD of up to 6 largest dominant masses (index lesions); no increase in size of other nodes (non-index lesions) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) Based on IRRC Assessments | From Week 9 until documented disease progression or study discontinuation (assessed up to June 2017, approximately 38 months) | DOR is defined as the time from first remission (CR or PR) to the date of initial objectively documented progression as determined using the revised International Working Group Criteria for non-Hodgkin Lymphoma, or death due to any cause, whichever occurs first. CR definition includes the complete disappearance of all evidence of disease, the definition of PR includes at least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses, and PD is defined as any new lesion or increase by \>50% of previously involved sites from nadir, as described in the IWG response criteria |
| Complete Remission Rate (CRR) Based on IRRC Assessment | From Week 9 until documented disease progression or study discontinuation (assessed up to June 2017, approximately 38 months) | CRR is defined as the number of subjects with a BOR of CR according to the revised International Working Group Criteria for non-Hodgkin Lymphoma, divided by the number of treated participants and expressed as a percentage. CR=Disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of spleen, liver, and bone marrow involvement. |
| Partial Remission (PR) Rate Based on IRRC Assessment | From Week 9 until documented disease progression or study discontinuation (assessed up to June 2017, approximately 38 months) | PR rate is defined as the number of participants with a best overall response (BOR) of PR according to the 2007 International Working Group (IWG) criteria, based on IRRC assessment, divided by the number of treated participants and expressed as a percentage. PR=Regression of measurable disease and no new sites; no increase in size of liver or spleen. \>=50% decrease in SPD of up to 6 largest dominant masses (index lesions); no increase in size of other nodes (non-index lesions) |
| Progression Free Survival (PFS) Based on IRRC Assessment | From Week 9 until documented disease progression or study discontinuation (assessed up to June 2017, approximately 38 months) | PFS was summarized descriptively using the Kaplan-Meier (KM) product-limit method. Median values of PFS, along with the two-sided 95% CIs were calculated using a method based on log-log transformation. |
| Overall Response Rate (ORR) Based on Investigator Assessments | From Week 9 until documented disease progression or study discontinuation (assessed up to June 2017, approximately 38 months) | ORR is determined by investigator assessments according to the revised International Working Group Criteria for non-Hodgkin Lymphoma. ORR is defined as the number of subjects with a best overall response (BOR) of complete response (CR) or partial response (PR) and is expressed as a percentage of all treated participants. CR=Disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of spleen, liver, and bone marrow involvement. PR=Regression of measurable disease and no new sites; no increase in size of liver or spleen. \>=50% decrease in SPD of up to 6 largest dominant masses (index lesions); no increase in size of other nodes (non-index lesions) |
Countries
Australia, Belgium, Canada, France, Germany, Italy, Norway, Singapore, Spain, Sweden, United Kingdom, United States
Participant flow
Pre-assignment details
116 participants were enrolled; 92 received study treatment. Participants were enrolled but not treated because they no longer met study criteria (n=20), withdrew consent (n=1), or for other reasons (n=3).
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: Nivolumab Nivolumab 3mg/kg intravenously every 2 weeks until disease progression or discontinuation due to toxicity | 92 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 5 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Other reasons | 2 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Arm 1: Nivolumab |
|---|---|
| Age, Continuous | 65.2 years STANDARD_DEVIATION 10.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 49 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 38 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 87 Participants |
| Sex: Female, Male Female | 44 Participants |
| Sex: Female, Male Male | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 36 / 92 |
| other Total, other adverse events | 89 / 92 |
| serious Total, serious adverse events | 46 / 92 |
Outcome results
Primary
Overall Response Rate (ORR) as Determined by IRRC
ORR is determined by an independent radiologic review committee (IRRC) according to the revised International Working Group Criteria for non-Hodgkin Lymphoma. ORR is defined as the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) and expressed as a percentage of all treated participants. CR=Disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of spleen, liver, and bone marrow involvement. PR=Regression of measurable disease and no new sites; no increase in size of liver or spleen. \>=50% decrease in SPD of up to 6 largest dominant masses (index lesions); no increase in size of other nodes (non-index lesions)
Time frame: From Week 9 until documented disease progression or study discontinuation (assessed up to June 2017, approximately 38 months)
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Nivolumab | Overall Response Rate (ORR) as Determined by IRRC | 4.3 Percentage of participants |
Secondary
Complete Remission Rate (CRR) Based on IRRC Assessment
CRR is defined as the number of subjects with a BOR of CR according to the revised International Working Group Criteria for non-Hodgkin Lymphoma, divided by the number of treated participants and expressed as a percentage. CR=Disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of spleen, liver, and bone marrow involvement.
Time frame: From Week 9 until documented disease progression or study discontinuation (assessed up to June 2017, approximately 38 months)
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Nivolumab | Complete Remission Rate (CRR) Based on IRRC Assessment | 1.1 Percentage of participants |
Secondary
Duration of Response (DOR) Based on IRRC Assessments
DOR is defined as the time from first remission (CR or PR) to the date of initial objectively documented progression as determined using the revised International Working Group Criteria for non-Hodgkin Lymphoma, or death due to any cause, whichever occurs first. CR definition includes the complete disappearance of all evidence of disease, the definition of PR includes at least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses, and PD is defined as any new lesion or increase by \>50% of previously involved sites from nadir, as described in the IWG response criteria
Time frame: From Week 9 until documented disease progression or study discontinuation (assessed up to June 2017, approximately 38 months)
Population: All treated participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: Nivolumab | Duration of Response (DOR) Based on IRRC Assessments | 10.94 months |
Secondary
Overall Response Rate (ORR) Based on Investigator Assessments
ORR is determined by investigator assessments according to the revised International Working Group Criteria for non-Hodgkin Lymphoma. ORR is defined as the number of subjects with a best overall response (BOR) of complete response (CR) or partial response (PR) and is expressed as a percentage of all treated participants. CR=Disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of spleen, liver, and bone marrow involvement. PR=Regression of measurable disease and no new sites; no increase in size of liver or spleen. \>=50% decrease in SPD of up to 6 largest dominant masses (index lesions); no increase in size of other nodes (non-index lesions)
Time frame: From Week 9 until documented disease progression or study discontinuation (assessed up to June 2017, approximately 38 months)
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Nivolumab | Overall Response Rate (ORR) Based on Investigator Assessments | 10.9 Percentage of participants |
Secondary
Partial Remission (PR) Rate Based on IRRC Assessment
PR rate is defined as the number of participants with a best overall response (BOR) of PR according to the 2007 International Working Group (IWG) criteria, based on IRRC assessment, divided by the number of treated participants and expressed as a percentage. PR=Regression of measurable disease and no new sites; no increase in size of liver or spleen. \>=50% decrease in SPD of up to 6 largest dominant masses (index lesions); no increase in size of other nodes (non-index lesions)
Time frame: From Week 9 until documented disease progression or study discontinuation (assessed up to June 2017, approximately 38 months)
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Nivolumab | Partial Remission (PR) Rate Based on IRRC Assessment | 3.3 Percentage of participants |
Secondary
Progression Free Survival (PFS) Based on IRRC Assessment
PFS was summarized descriptively using the Kaplan-Meier (KM) product-limit method. Median values of PFS, along with the two-sided 95% CIs were calculated using a method based on log-log transformation.
Time frame: From Week 9 until documented disease progression or study discontinuation (assessed up to June 2017, approximately 38 months)
Population: All treated participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: Nivolumab | Progression Free Survival (PFS) Based on IRRC Assessment | 2.20 months |