Hodgkin Disease, Lymphoma, Non-Hodgkin
Conditions
Keywords
Pediatric, Lymphoma, Non-Hodgkin, Hodgkin Disease, Relatlimab, Nivolumab, Lymphocyte Activation Gene-3, Lymphoma, Large B-Cell, Diffuse, Primary Mediastinal B-cell Lymphoma, Lymphoma, Large-Cell, Anaplastic, Burkitt lymphoma, Lymphoblastic lymphoma, NK/ T-cell lymphoma, Peripheral T-cell lymphoma
Brief summary
The purpose of this study is to assess the safety, tolerability, drug levels, and preliminary efficacy of relatlimab plus nivolumab in pediatric and young adult participants with recurrent or refractory classical Hodgkin lymphoma and non-Hodgkin lymphoma.
Interventions
DRUGRelatlimab
Specified Dose on Specified Days
DRUGNivolumab
Specified Dose on Specified Days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 30 Years
Healthy volunteers
No
Inclusion criteria
* Participants with pathologically confirmed high-risk R/R cHL, after non-response to or failure of 1or more lines of standard therapy. * Participants with pathologically confirmed R/R NHL after non-response to or failure of 1or more lines of standard therapy, including, but not limited to, R/R primary mediastinal B-cell lymphoma, diffuse large B-cell lymphoma (DLBCL), mediastinal gray zone lymphoma (MGZL), anaplastic large cell lymphoma (ALCL), or peripheral T-cell lymphoma (PTCL). * Participants with pathologically confirmed R/R NHL after non-response to or failure of 2 or more lines of standard therapy, including Burkitt lymphoma (blast count \<25% malignant Burkitt cells and/or per the investigator's clinical assessment of risk status), lymphoblastic lymphoma (blast count \< 25% of marrow nucleated cells and/or per the investigator's clinical assessment of risk status), NK/T-cell lymphoma (nasal and non-nasal NK/T-cell lymphoma subtypes, but not aggressive NK/T-cell leukemia/lymphoma subtype). * The participant's current disease state must be R/R to standard therapy. * Participants must have measurable PET positive disease in both cHL and NHL cohorts.
Exclusion criteria
* Primary CNS lymphoma of the brain or spinal cord, and secondary CNS lymphoma (ie, from systemic non-Hodgkin lymphoma) involving the brain, spinal cord, or with leptomeningeal seeding. * Prior treatment with an anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways, with the exception of anti-PD(L)-1 targeted therapies. * Prior treatment with lymphocyte activation gene-3 (LAG-3)-targeted agents. * Participants with clinically significant systemic illnesses unrelated to the cancer as judged by the investigators, which would compromise the participant's ability to tolerate the study treatment. * Participants with autoimmune disease. * Prior allogeneic bone marrow transplantation. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-Limiting Toxicities (DLTs) - Part A | 1 cycle, defined as 28 days | Hepatic DLT * ALT or AST \> 8 × ULN * ALT or AST \> 5 and ≤ 8 × ULN, that fails to return to ≤ Grade 1 within 2 weeks despite medical intervention. * TB \> 5 × ULN. * ALT or AST \> 3 × ULN and concurrent total bilirubin \> 2 × ULN. Non-Hematologic DLT * ≥ Grade 2 episcleritis, uveitis, iritis or any other immune-related eye pain or reduction in visual acuity that requires systemic treatment. * ≥ Grade 3 non-hepatic or non-hematologic toxicity with the exceptions noted below. Hematologic DLT * Grade 4 anemia not explained by underlying disease. * Grade 3 febrile neutropenia lasting \> 48 hours, or Grade 4 febrile neutropenia * Grade 4 neutropenia that does not resolve to Grade 3 or less within 5 days of initiation of granulocyte colony stimulating factor. * Grade 3 thrombocytopenia associated with clinically significant bleeding. * Grade 3 hemolysis |
| Complete Metabolic Response (CMR) Rate - Part B | From first dose until the first documented response | The CMR rate is defined as the percentage of all response-evaluable participants who achieve the best response of CMR using Lugano 2014 criteria. No participants enrolled in Part B. |
| Number of Participants With Adverse Events (AEs) - Part A | From first dose to 135 days post last dose (Up to approximately 11 months) | An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment that does not necessarily have a causal relationship with this treatment. |
| Number of Participants Who Died - Part A | from first dose to 135 days post last dose (Up to approximately 11 months) | Number of participants who died due to any cause |
| Number of Participants With Serious Adverse Events (SAEs) - Part A | from first dose to 135 days post last dose (Up to approximately 11 months) | Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, and requires inpatient hospitalization or causes prolongation of existing hospitalization. |
| Number of Participants With Adverse Events (AEs) Leading to Discontinuation - Part A | From first dose to 135 days post last dose (Up to approximately 11 months) | An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment that does not necessarily have a causal relationship with this treatment. |
| Number of Participants With Laboratory Abnormalities - Part A | From first dose to 30 days post last dose (Up to approximately 8 months) | Number of participants with Grade ≥ 3 laboratory abnormalities in hematology and serum chemistry. Grade 3=severe Grade 4=life-threatening Grade 5=death |
| Maximum Serum Concentration (Cmax) | Cycle 1 Day 1 | Maximum observed serum concentration of Analyte BMS-986016 |
| Time to Maximum Concentration (Tmax) | Cycle 1 Day 1 | Time of maximum observed serum concentration of Analyte BMS-986016 |
| Area Under the Concentration-time Curve [AUC(TAU)] | Cycle 1 Day 1 | Area Under the Concentration-time Curve \[AUC(TAU)\] for Analyte BMS-986016 |
| Concentration Trough (Ctrough) | Cycle 2 Day 1, Cycle 4 Day 1, Cycle 6 Day 1 | Concentration Trough (Ctrough) for Analyte BMS-986016 and BMS-936558 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) - Part B | From first dose to 135 days post last dose | An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment that does not necessarily have a causal relationship with this treatment. No participants enrolled in part B. |
| Number of Participants With Serious Adverse Events (SAEs) - Part B | From first dose to 135 days post last dose | Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, and requires inpatient hospitalization or causes prolongation of existing hospitalization. No participants enrolled in part B. |
| Number of Participants With Adverse Events Leading to Discontinuation - Part B | From first dose to 135 days post last dose | An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment that does not necessarily have a causal relationship with this treatment. No participants enrolled in part B. |
| Number of Participants Who Died - Part B | From first dose to 135 days post last dose | Number of participants who died due to any cause. No participants enrolled in part B. |
| Number of Participants With Laboratory Abnormalities - Part B | From first dose to 135 days post last dose | No participants enrolled in part B. |
| Objective Response Rate (ORR) - Part B | From to | ORR is defined as the percentage of all response evaluable participants who achieve a best response of CMR or PMR using the Lugano 2014 classification. No participants enrolled in part B |
Countries
Australia, France, Italy, Netherlands, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Participant flow
Pre-assignment details
Only Part A was initiated prior to early study termination. Part B was not initiated.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 5 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 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 | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 1 / 1 |
| other Total, other adverse events | 4 / 4 | 1 / 1 |
| serious Total, serious adverse events | 1 / 4 | 1 / 1 |
Outcome results
None listed