Brief Summary
The purpose of this study is to determine whether nivolumab plus brentuximab vedotin (followed by brentuximab vedotin plus bendamustine in patient with suboptimal response) is safe and effective in treating patients with Hodgkin's lymphoma (cHL). Eligible patients are children, adolescents, and young adults relapsed or refractory to first line.
Brief Title
A Study of Nivolumab Plus Brentuximab Vedotin in Patients Between 5 and 30 Years Old, With Hodgkin's Lymphoma (cHL), Relapsed or Refractory From First Line Treatment
Categories
Completion Date
Completion Date Type
Actual
Conditions
Hodgkin Disease
Eligibility Criteria
Inclusion Criteria:
* Classic Hodgkin Lymphoma (cHL), relapsed or refractory
* Minimal limitation on activities of daily living as measured by Karnofsky ≥ 50 for participants \> 16 years of age or Lansky ≥ 50 for participants ≤ 16 years of age.
* One prior anti-cancer therapy that did not work
Exclusion Criteria:
* Active, known, or suspected autoimmune disease or infection
* Active cerebral/meningeal disease related to the underlying malignancy
* More than one line of anti-cancer therapy or no treatment at all
* Received a stem cell transplant for Hodgkin Lymphoma and/or a solid organ transplant
* Prior treatment with any drug that targets T cell co-stimulation pathways (such as checkpoint inhibitors)
Other protocol defined inclusion/exclusion criteria apply
* Classic Hodgkin Lymphoma (cHL), relapsed or refractory
* Minimal limitation on activities of daily living as measured by Karnofsky ≥ 50 for participants \> 16 years of age or Lansky ≥ 50 for participants ≤ 16 years of age.
* One prior anti-cancer therapy that did not work
Exclusion Criteria:
* Active, known, or suspected autoimmune disease or infection
* Active cerebral/meningeal disease related to the underlying malignancy
* More than one line of anti-cancer therapy or no treatment at all
* Received a stem cell transplant for Hodgkin Lymphoma and/or a solid organ transplant
* Prior treatment with any drug that targets T cell co-stimulation pathways (such as checkpoint inhibitors)
Other protocol defined inclusion/exclusion criteria apply
Inclusion Criteria
Inclusion Criteria:
* Classic Hodgkin Lymphoma (cHL), relapsed or refractory
* Minimal limitation on activities of daily living as measured by Karnofsky ≥ 50 for participants \> 16 years of age or Lansky ≥ 50 for participants ≤ 16 years of age.
* One prior anti-cancer therapy that did not work
inclusion/
* Classic Hodgkin Lymphoma (cHL), relapsed or refractory
* Minimal limitation on activities of daily living as measured by Karnofsky ≥ 50 for participants \> 16 years of age or Lansky ≥ 50 for participants ≤ 16 years of age.
* One prior anti-cancer therapy that did not work
inclusion/
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
30 Years
Minimum Age
5 Years
NCT Id
NCT02927769
Org Class
Industry
Org Full Name
Bristol-Myers Squibb
Org Study Id
CA209-744
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Risk-based, Response-adapted, Phase II Open-label Trial of Nivolumab + Brentuximab Vedotin (N + Bv) for Children, Adolescents, and Young Adults With Relapsed/Refractory (R/R) CD30 + Classic Hodgkin Lymphoma (cHL) After Failure of First-line Therapy, Followed by Brentuximab + Bendamustine (Bv + B) for Participants With a Suboptimal Response (CheckMate 744: CHECKpoint Pathway and Nivolumab Clinical Trial Evaluation)
Primary Outcomes
Outcome Description
The complete metabolic response (CMR) rate is defined as the percent of all response-evaluable participants who, assessed by the BICR, achieved best response of CMR.
Complete metabolic response (CMR):
* Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
* New lesions: No
* Bone marrow: No FDG-avid disease Participants who stopped study treatment early for toxicity without a CMR were evaluable.
Confidence interval is based on the Clopper and Pearson method
Complete metabolic response (CMR):
* Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
* New lesions: No
* Bone marrow: No FDG-avid disease Participants who stopped study treatment early for toxicity without a CMR were evaluable.
Confidence interval is based on the Clopper and Pearson method
Outcome Measure
Complete Metabolic Response (CMR) Rate at Any Time Prior to Radiation Therapy by Blinded Independent Centralized Review (BICR) - Cohort 1
Outcome Time Frame
From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks).
Outcome Description
Event Free Survival (EFS) is the time from the first treatment to the earliest occurrence of composite events including: Disease progression (PD), Failure to achieve complete metabolic response (CMR) after 4 cycles of N+Bv and 2 cycles of Bv+B, Secondary malignancy, Death .
PD :
Lymph Nodes and Lesions: new growth or increase of \>= 50% in size from nadir. New or growing lesions outside the lymph nodes.
Spleen: Significant increase in spleen size, either from a previously enlarged state or from normal size.
New Lesions: Yes Bone Marrow: New or returning FDG-avid disease
CMR:
Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale New lesions: No Bone marrow: No FDG-avid disease Participants without an "event" were censored at the last tumor assessment. Those who started subsequent anticancer therapy without a prior "event" were censored at the last tumor assessment prior to or upon starting subsequent therapy.
Based on Kaplan-Meier Estimates.
PD :
Lymph Nodes and Lesions: new growth or increase of \>= 50% in size from nadir. New or growing lesions outside the lymph nodes.
Spleen: Significant increase in spleen size, either from a previously enlarged state or from normal size.
New Lesions: Yes Bone Marrow: New or returning FDG-avid disease
CMR:
Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale New lesions: No Bone marrow: No FDG-avid disease Participants without an "event" were censored at the last tumor assessment. Those who started subsequent anticancer therapy without a prior "event" were censored at the last tumor assessment prior to or upon starting subsequent therapy.
Based on Kaplan-Meier Estimates.
Outcome Measure
Event-free Survival (EFS) Rate at 3 Years by Blinded Independent Centralized Review (BICR) - Cohort 1
Outcome Time Frame
At 3 years post first dose of study therapy
Outcome Description
The complete metabolic response (CMR) rate is defined as the percent of all response-evaluable participants who, assessed by the BICR, achieved best response of CMR.
Complete metabolic response (CMR):
* Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
* New lesions: No
* Bone marrow: No FDG-avid disease Participants who came off study treatment early for toxicity without a CMR were evaluable.
Confidence interval is based on the Clopper and Pearson method
Complete metabolic response (CMR):
* Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
* New lesions: No
* Bone marrow: No FDG-avid disease Participants who came off study treatment early for toxicity without a CMR were evaluable.
Confidence interval is based on the Clopper and Pearson method
Outcome Measure
Complete Metabolic Response (CMR) Rate at Any Time Prior to High Dose Chemotherapy Followed by Autologous Stem Cell Treatment (HDCT/ASCT) by Blinded Independent Centralized Review (BICR) - Cohort 2
Outcome Time Frame
From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks)
Secondary Ids
Secondary Id
2016-002347-41
Secondary Outcomes
Outcome Description
Overall response rate (ORR) is defined as the percent of all response-evaluable participants who, assessed by the BICR, achieved a best response of complete metabolic response (CMR) or partial metabolic response (PMR).
Complete metabolic response (CMR):
* Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
* New lesions: No
* Bone marrow: No FDG-avid disease
Partial metabolic response (PMR):
* Lymph nodes/extralymphatic: Score 4 or 5, reduced uptake from baseline
* New lesions: None
* Bone marrow: Residual uptake higher than normal, reduced from baseline. Participants who came off early for toxicity without CMR or PMR were evaluable.
Complete metabolic response (CMR):
* Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
* New lesions: No
* Bone marrow: No FDG-avid disease
Partial metabolic response (PMR):
* Lymph nodes/extralymphatic: Score 4 or 5, reduced uptake from baseline
* New lesions: None
* Bone marrow: Residual uptake higher than normal, reduced from baseline. Participants who came off early for toxicity without CMR or PMR were evaluable.
Outcome Time Frame
From first dose to PMR or CMR within 4 cycles of therapy, or the completion of four cycles of therapy (N+Bv x4) (up to approximately 12 weeks).
Outcome Measure
Overall Response Rate (ORR) Following 4 Cycles of Nivolumab + Brentuximab Vedotin Treatment by Blinded Independent Centralized Review (BICR)
Outcome Description
Progression Free Survival (PFS) is the time from the date of first treatment to the date of first documented disease progression by BICR or death.
Progressive Disease (PD):
Lymph Nodes and Lesions: new growth or increase of \>= 50% in size from nadir. New or growing lesions outside the lymph nodes.
Spleen: Significant increase in spleen size, either from a previously enlarged state or from normal size.
New Lesions: Yes Bone Marrow: New or returning FDG-avid disease. Participants who neither progressed nor died were censored at the last adequate tumor assessment. Participants who started subsequent anticancer therapy (that is not part of high dose chemotherapy followed by autologous stem cell transplant (HDCT/ASCT) Consolidation Therapy for R2 Cohort) without a prior reported progression or death were censored at the last tumor assessment prior to initiation of the subsequent anticancer therapy.
Based on Kaplan-Meier Estimates.
Progressive Disease (PD):
Lymph Nodes and Lesions: new growth or increase of \>= 50% in size from nadir. New or growing lesions outside the lymph nodes.
Spleen: Significant increase in spleen size, either from a previously enlarged state or from normal size.
New Lesions: Yes Bone Marrow: New or returning FDG-avid disease. Participants who neither progressed nor died were censored at the last adequate tumor assessment. Participants who started subsequent anticancer therapy (that is not part of high dose chemotherapy followed by autologous stem cell transplant (HDCT/ASCT) Consolidation Therapy for R2 Cohort) without a prior reported progression or death were censored at the last tumor assessment prior to initiation of the subsequent anticancer therapy.
Based on Kaplan-Meier Estimates.
Outcome Time Frame
At 3 years post first dose of study therapy
Outcome Measure
Progression Free Survival (PFS) Rate at 3 Years by Blinded Independent Centralized Review (BICR)
Outcome Description
Duration of response (DOR) is the time from first complete metabolic response or partial metabolic response (CMR or PMR) to event free survival EFS (Cohort 1)/progression free survival PFS (Cohort 2) event. For participants with no event, DOR was censored on the date of last tumor assessment.
Participants who started subsequent anticancer therapy (not part of high-dose chemotherapy followed by autologous stem cell transplant HDCT/ASCT) without a prior reported EFS/PFS event were censored at the last tumor assessment prior to initiation of the subsequent therapy.
Complete metabolic response (CMR):
* Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
* New lesions: No
* Bone marrow: No FDG-avid disease
Partial metabolic response (PMR):
* Lymph nodes/extralymphatic: Score 4 or 5, reduced uptake from baseline
* New lesions: None
* Bone marrow: Residual uptake higher than normal, reduced from baseline. Based on Kaplan-Meier estimates
Participants who started subsequent anticancer therapy (not part of high-dose chemotherapy followed by autologous stem cell transplant HDCT/ASCT) without a prior reported EFS/PFS event were censored at the last tumor assessment prior to initiation of the subsequent therapy.
Complete metabolic response (CMR):
* Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
* New lesions: No
* Bone marrow: No FDG-avid disease
Partial metabolic response (PMR):
* Lymph nodes/extralymphatic: Score 4 or 5, reduced uptake from baseline
* New lesions: None
* Bone marrow: Residual uptake higher than normal, reduced from baseline. Based on Kaplan-Meier estimates
Outcome Time Frame
From first dose until disease progression, start of subsequent anti-cancer therapy, or or death due to any cause (up to approximately 86 months)
Outcome Measure
Duration of Response (DOR) by Blinded Independent Centralized Review (BICR)
Outcome Description
The complete metabolic response (CMR) rate is defined as the percent of all response-evaluable participants who, assessed by the investigator, achieved best response of CMR.
Complete metabolic response (CMR):
* Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
* New lesions: No
* Bone marrow: No FDG-avid disease Participants who come off early for toxicity without a CMR were evaluable. Confidence interval is based on the Clopper and Pearson method
Complete metabolic response (CMR):
* Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
* New lesions: No
* Bone marrow: No FDG-avid disease Participants who come off early for toxicity without a CMR were evaluable. Confidence interval is based on the Clopper and Pearson method
Outcome Time Frame
From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks).
Outcome Measure
Complete Metabolic Response (CMR) Rate at Any Time Prior to Radiation Therapy by Investigator - Cohort 1
Outcome Description
Event Free Survival (EFS) is the time from the first treatment to the earliest occurrence of composite events including: Disease progression (PD), Failure to achieve complete metabolic response (CMR) after 4 cycles of N+Bv and 2 cycles of Bv+B, Secondary malignancy, Death .
PD :
Lymph Nodes and Lesions: new growth or increase of \>= 50% in size from nadir. New or growing lesions outside the lymph nodes.
Spleen: Significant increase in spleen size, either from a previously enlarged state or from normal size.
New Lesions: Yes Bone Marrow: New or returning FDG-avid disease
CMR:
Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale New lesions: No Bone marrow: No FDG-avid disease Participants without an "event" were censored at the last tumor assessment. Those who started subsequent anticancer therapy without a prior "event" were censored at the last tumor assessment prior to or upon starting subsequent therapy.
Based on Kaplan-Meier Estimates.
PD :
Lymph Nodes and Lesions: new growth or increase of \>= 50% in size from nadir. New or growing lesions outside the lymph nodes.
Spleen: Significant increase in spleen size, either from a previously enlarged state or from normal size.
New Lesions: Yes Bone Marrow: New or returning FDG-avid disease
CMR:
Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale New lesions: No Bone marrow: No FDG-avid disease Participants without an "event" were censored at the last tumor assessment. Those who started subsequent anticancer therapy without a prior "event" were censored at the last tumor assessment prior to or upon starting subsequent therapy.
Based on Kaplan-Meier Estimates.
Outcome Time Frame
At 3 years post first dose of study therapy
Outcome Measure
Event-free Survival (EFS) Rate at 3 Years by Investigator - Cohort 1
Outcome Description
The complete metabolic response (CMR) rate is defined as the percent of all response-evaluable participants who, assessed by the investigator, achieved best response of CMR.
Complete metabolic response (CMR):
* Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
* New lesions: No
* Bone marrow: No FDG-avid disease Participants who came off study treatment early for toxicity without a CMR were evaluable.
Confidence interval is based on the Clopper and Pearson method.
Complete metabolic response (CMR):
* Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
* New lesions: No
* Bone marrow: No FDG-avid disease Participants who came off study treatment early for toxicity without a CMR were evaluable.
Confidence interval is based on the Clopper and Pearson method.
Outcome Time Frame
From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks)
Outcome Measure
Complete Metabolic Response (CMR) Rate at Any Time Prior to High Dose Chemotherapy Followed by Autologous Stem Cell Treatment (HDCT/ASCT) by Investigator - Cohort 2
Outcome Description
Overall response rate (ORR) is defined as the percent of all response-evaluable participants who, assessed by the investigator, achieve a best response of complete metabolic response (CMR) or partial metabolic response (PMR).
Complete metabolic response (CMR):
* Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
* New lesions: No
* Bone marrow: No FDG-avid disease
Partial metabolic response:
* Lymph nodes/extralymphatic: Score 4 or 5, reduced uptake from baseline
* New lesions: None
* Bone marrow: Residual uptake higher than normal, reduced from baseline Participants who came off early for toxicity without CMR or PMR were evaluable.
Complete metabolic response (CMR):
* Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
* New lesions: No
* Bone marrow: No FDG-avid disease
Partial metabolic response:
* Lymph nodes/extralymphatic: Score 4 or 5, reduced uptake from baseline
* New lesions: None
* Bone marrow: Residual uptake higher than normal, reduced from baseline Participants who came off early for toxicity without CMR or PMR were evaluable.
Outcome Time Frame
From first dose to PMR or CMR within 4 cycles of therapy, or the completion of four cycles of therapy (N+Bv x4) (up to approximately 12 weeks).
Outcome Measure
Overall Response Rate (ORR) Following 4 Cycles of Nivolumab + Brentuximab Vedotin Treatment by Investigator
Outcome Description
Progression Free Survival (PFS) is the time from the date of first treatment to the date of first documented disease progression by investigator or death.
Progressive Disease (PD):
Lymph Nodes and Lesions: new growth or increase of \>= 50% in size from nadir. New or growing lesions outside the lymph nodes.
Spleen: Significant increase in spleen size, either from a previously enlarged state or from normal size.
New Lesions: Yes Bone Marrow: New or returning FDG-avid disease. Participants who neither progressed nor died were be censored at the last adequate tumor assessment. Participants who started subsequent anticancer therapy (that is not part of high dose chemotherapy followed by autologous stem cell transplant (HDCT/ASCT) Consolidation Therapy forR2 Cohort) without a prior reported progression or death were censored at the last tumor assessment prior to initiation of the subsequent anticancer therapy.
Based on Kaplan-Meier Estimates.
Progressive Disease (PD):
Lymph Nodes and Lesions: new growth or increase of \>= 50% in size from nadir. New or growing lesions outside the lymph nodes.
Spleen: Significant increase in spleen size, either from a previously enlarged state or from normal size.
New Lesions: Yes Bone Marrow: New or returning FDG-avid disease. Participants who neither progressed nor died were be censored at the last adequate tumor assessment. Participants who started subsequent anticancer therapy (that is not part of high dose chemotherapy followed by autologous stem cell transplant (HDCT/ASCT) Consolidation Therapy forR2 Cohort) without a prior reported progression or death were censored at the last tumor assessment prior to initiation of the subsequent anticancer therapy.
Based on Kaplan-Meier Estimates.
Outcome Time Frame
At 3 years post first dose
Outcome Measure
Progression Free Survival (PFS) Rate at 3 Years by Investigator
Outcome Description
Duration of response (DOR) is the time from first complete metabolic response or partial metabolic response (CMR or PMR) to event free survival EFS (Cohort 1)/progression free survival PFS (Cohort 2) event. For participants with no event, the DOR was censored on the date of last tumor assessment.
Participants who started subsequent anticancer therapy (not part of high-dose chemotherapy followed by autologous stem cell transplant HDCT/ASCT) without a prior reported EFS/PFS event were censored at the last tumor assessment prior to initiation of the subsequent anticancer therapy.
Complete metabolic response (CMR):
* Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
* New lesions: No
* Bone marrow: No FDG-avid disease
Partial metabolic response:
* Lymph nodes/extralymphatic: Score 4 or 5, reduced uptake from baseline
* New lesions: None
* Bone marrow: Residual uptake higher than normal, reduced from baseline. Based on Kaplan-Meier estimates.
Participants who started subsequent anticancer therapy (not part of high-dose chemotherapy followed by autologous stem cell transplant HDCT/ASCT) without a prior reported EFS/PFS event were censored at the last tumor assessment prior to initiation of the subsequent anticancer therapy.
Complete metabolic response (CMR):
* Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
* New lesions: No
* Bone marrow: No FDG-avid disease
Partial metabolic response:
* Lymph nodes/extralymphatic: Score 4 or 5, reduced uptake from baseline
* New lesions: None
* Bone marrow: Residual uptake higher than normal, reduced from baseline. Based on Kaplan-Meier estimates.
Outcome Time Frame
From first dose until disease progression, start of subsequent anti-cancer therapy, or or death due to any cause (up to approximately 86 months)
Outcome Measure
Duration of Response (DOR) by Investigator
Outcome Description
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.
Outcome Time Frame
From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months).
Outcome Measure
The Number of Participants With Adverse Events (AEs)
Outcome Description
A Serious Adverse Event (SAE) is defined as 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
* Results in persistent or significant disability/incapacity
* Is a congenital anomaly/birth defect
* Is an important medical event.
* 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
* Results in persistent or significant disability/incapacity
* Is a congenital anomaly/birth defect
* Is an important medical event.
Outcome Time Frame
From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months)
Outcome Measure
The Number of Participants With Serious Adverse Events (SAEs)
Outcome Description
The Number of Participants with Abnormal Laboratory Values for Specific Thyroid Tests.
Outcome Time Frame
From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months)
Outcome Measure
The Number of Participants With Abnormal Laboratory Values for Specific Thyroid Tests
Outcome Description
The Number of Participants with Abnormal Laboratory Values for Liver Tests.
Outcome Time Frame
From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months)
Outcome Measure
The Number of Participants With Abnormal Laboratory Values for Liver Tests
Outcome Description
Temperature, blood pressure, and heart rate abnormalities reported as adverse events.
Outcome Time Frame
From first dose to 100 days after last dose of study therapy (assessed for an average of 7 months up until a maximum of 10 months).
Outcome Measure
Number of Participants With Abnormal Vital Signs Reported as Adverse Events
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Maximum Age Number (converted to Years and rounded down)
30
Minimum Age Number (converted to Years and rounded down)
5
Investigators
Investigator Type
Principal Investigator
Investigator Name
Lisa Gennarini
Investigator Email
lfigueir@montefiore.org
Investigator Phone