The purpose of this study is to determine whether Nivolumab, in combination with brentuximab vedotin, is safe and effective in patients with certain subtypes of non-Hodgkin's lymphomas with CD30 expression that have not responded to treatment or have come back. The subtypes we are studying are Diffuse Large B-Cell Lymphoma (DLBCL), Peripheral T-Cell Lymphoma (PTCL), Cutaneous T-Cell Lymphoma (CTCL), Primary Mediastinal Large B-Cell Lymphoma (PMBL) and Mediastinal Gray Zone Lymphoma (MGZL).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
145
Local Institution - 0017
Birmingham, Alabama, United States
University Of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, United States
Local Institution - 0012
Tampa, Florida, United States
Winship Cancer Institute.
Atlanta, Georgia, United States
University Of Chicago
Chicago, Illinois, United States
Mayo Clinic
Rochester, Minnesota, United States
Washington University School Of Medicine
St Louis, Missouri, United States
Local Institution - 0003
New York, New York, United States
Local Institution - 0010
New York, New York, United States
University Of Rochester
Rochester, New York, United States
...and 17 more locations
Safety Analysis - Number of Participants With Dose Limiting Toxicities (DLT) in the DLT Evaluation Phase
DLTs are defined as any study drug-related toxicity (brentuximab vedotin or nivolumab) that requires either a dose reduction or delay of more than 7 days of either study drug in Cycle 2 or delays the Cycle 3 Day 1 administration of combined treatment by more than 7 days.
Time frame: From first dose of treatment to 6 weeks after first dose
Safety Analysis - Number of Participant Deaths
Number of participant Deaths
Time frame: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
Safety Analysis - Number of Participants With Adverse Advents
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.
Time frame: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
Safety Analysis - Number of Participants With Serious Adverse Events
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. * results in persistent or significant disability/incapacity * is a congenital anomaly/birth defect * is an important medical event
Time frame: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
Safety Analysis - Number of Participants With Adverse Events Leading to Discontinuation
Number of participants with adverse events leading to discontinuation
Time frame: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
Safety Analysis - Number of Participants With Adverse Events Leading to Dose Delay or Reduction
Number of participants with adverse events leading to dose delay or reduction
Time frame: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
Safety Analysis - Number of Participants With Drug Related Adverse Events
Number of participants with Drug Related Adverse Events
Time frame: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
Safety Analysis - Percentage of Participants With Thyroid Test Abnormalities
Percentage of participants with specific thyroid test abnormalities
Time frame: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
Safety Analysis - Percentage of Participants With Liver Test Abnormalities
Percentage of participants with specific Liver test abnormalities
Time frame: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
Objective Response Rate (ORR)
The percentage of participants with a best overall response (BOR) of CR or PR. DLBCL, PTCL, PMBL \& MGZL complete and partial response are outlined in the Lugano Classification 2014 and Lymphoma Response to Immunomodulatory therapy Criteria. CTCL complete and partial response are defined in The consensus Global Response Score assessment.
Time frame: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
Duration of Response (DOR)
DOR will be calculated from the date of initial documentation of a response (CR, or PR) to the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death due to any cause, whichever occurs first. DLBCL, PTCL, PMBL \& MGZL complete and partial response are outlined in the Lugano Classification 2014 and Lymphoma Response to Immunomodulatory therapy Criteria. CTCL complete and partial response are defined in The consensus Global Response Score assessment.
Time frame: From the first patient first visit to 8 months after the last patient first visit (up to 48 months)
Complete Response Rate (CRR)
The CRR is defined as the percentage of participants with a BOR (Best overall response) of CR divided by the number of treated participants. DLBCL, PTCL, PMBL \& MGZL (CR) 1.Complete disappearance of all detectable clinical evidence of disease. 2.Bone marrow: No evidence of FDG- avid disease in marrow. CTCL (CR) 1. 100% clearance of skin lesions. 2. all lymph nodes ≤1.5 cm, N3 classification and ≤ 1.5 cm in their long axis and \> 1 cm in their short axis at baseline, must be ≤ 1 cm in their short axis or biopsy negative for lymphoma. 3. organs should not be enlarged on examination or imaging 4. absence of blood involvement
Time frame: From first dose to the date of initial objectively documented progression or the date of subsequent therapy, whichever occurs first (up to 48 months)
Duration of Complete Response
The duration of CR will only be evaluated in participants with BOR of CR and is defined as the time from first documentation of CR to the date of relapse or death due to any cause, whichever occurs first. DLBCL, PTCL, PMBL \& MGZL (CR) 1.Complete disappearance of all detectable clinical evidence of disease. 2.Bone marrow: No evidence of FDG- avid disease in marrow. CTCL (CR) 1. 100% clearance of skin lesions. 2. all lymph nodes ≤1.5 cm, N3 classification and ≤ 1.5 cm in their long axis and \> 1 cm in their short axis at baseline, must be ≤ 1 cm in their short axis or biopsy negative for lymphoma. 3. organs should not be enlarged on examination or imaging 4. absence of blood involvement
Time frame: From first dose to the date of relapse or death due to any cause, whichever occurs first. (about 48 months)
Progression Free Survival (PFS)
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PFS is defined as the time from the date of first dose of study drug until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death due to any cause, whichever comes first. Participants who are progression-free and alive or have unknown status will be censored at the last tumor assessment. Participants who did not have any onstudy tumor assessments and did not die will be censored on the date of first treatment. For participants who received subsequent therapy prior to documented progression, it will be censored on the last tumor assessment date prior to or on subsequent therapy.
Time frame: From first dose of study drug until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death due to any cause, whichever comes first. (about 48 months)
Overall Survival (OS)
OS is defined as the time from the date of first dose of study drug until the date of death (any reason). If the participant is alive or the vital status is unknown, the participant will be censored at the date the participant was last known to be alive.
Time frame: From the first patient first visit to 8 months after the last patient first visit (about 48 months)