An Investigational Immuno-therapy Safety and Effectiveness Study of Nivolumab in Combination With Brentuximab Vedotin to Treat Non-Hodgkin Lymphomas
- Conditions
- Non-Hodgkin's Disease
- Interventions
- Biological: Nivolumab
- Registration Number
- NCT02581631
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 145
- Relapsed/refractory diffuse large B cell lymphoma (DLBCL), relapsed/refractory peripheral T cell lymphoma (PTCL) (all subtypes excluding anaplastic large cell lymphoma), relapsed/refractory Cutaneous T cell lymphoma (CTCL) mycosis fungoides/sezary syndrome (MF/SS), relapsed/refractory primary mediastinal B lymphoma (PMBL), and relapsed/refractory mediastinal gray zone lymphoma (MGZL)
- Expression of CD30
- Subjects must be 18 years or older (≥ 15 years for PMBL)
- Known central nervous system (CNS) lymphomas; Active cerebral/meningeal disease related to the underlying malignancy
- Active, known, or suspected autoimmune disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Nivolumab+Brentuximab Vedotin Brentuximab Vedotin Nivolumab+Brentuximab Vedotin dose as specified Nivolumab+Brentuximab Vedotin Nivolumab Nivolumab+Brentuximab Vedotin dose as specified
- Primary Outcome Measures
Name Time Method Safety Analysis - Number of Participants With Dose Limiting Toxicities (DLT) in the DLT Evaluation Phase From first dose of treatment to 6 weeks after first dose 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.
Safety Analysis - Number of Participant Deaths CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months Number of participant Deaths
Safety Analysis - Number of Participants With Adverse Advents CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months 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.
Safety Analysis - Number of Participants With Serious Adverse Events CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months 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 eventSafety Analysis - Number of Participants With Adverse Events Leading to Discontinuation CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months Number of participants with adverse events leading to discontinuation
Safety Analysis - Number of Participants With Adverse Events Leading to Dose Delay or Reduction CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months Number of participants with adverse events leading to dose delay or reduction
Safety Analysis - Number of Participants With Drug Related Adverse Events CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months Number of participants with Drug Related Adverse Events
Safety Analysis - Percentage of Participants With Thyroid Test Abnormalities CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months Percentage of participants with specific thyroid test abnormalities
Safety Analysis - Percentage of Participants With Liver Test Abnormalities CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months Percentage of participants with specific Liver test abnormalities
Objective Response Rate (ORR) CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months 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.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) From the first patient first visit to 8 months after the last patient first visit (up to 48 months) 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.Complete Response Rate (CRR) From first dose to the date of initial objectively documented progression or the date of subsequent therapy, whichever occurs first (up to 48 months) 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 involvementDuration of Complete Response From first dose to the date of relapse or death due to any cause, whichever occurs first. (about 48 months) 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 involvementProgression Free Survival (PFS) 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) 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.
Overall Survival (OS) From the first patient first visit to 8 months after the last patient first visit (about 48 months) 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.
Trial Locations
- Locations (27)
Winship Cancer Institute.
🇺🇸Atlanta, Georgia, United States
University Of Chicago
🇺🇸Chicago, Illinois, United States
Local Institution - 0003
🇺🇸New York, New York, United States
Hopital Saint Louis
🇫🇷Paris, France
BC Cancer Agency - Vancouver Centre
🇨🇦Vancouver, British Columbia, Canada
Royal Marsden Hospital
🇬🇧Sutton, Surrey, United Kingdom
Local Institution - 0017
🇺🇸Birmingham, Alabama, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
University Of Miami Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Local Institution - 0012
🇺🇸Tampa, Florida, United States
Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
University of Washington - Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Washington University School Of Medicine
🇺🇸Saint Louis, Missouri, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Local Institution - 0010
🇺🇸New York, New York, United States
The Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Local Institution - 0020
🇫🇷Pierre Benite Cedex, France
Bon Secours-St Francis Hosp
🇺🇸Greenville, South Carolina, United States
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
Local Institution - 0011
🇨🇦Toronto, Ontario, Canada
Local Institution - 0018
🇮🇹Bergamo, Italy
Local Institution - 0024
🇮🇹Bologna, Italy
Local Institution - 0027
🇪🇸Hospitalet de Llobregat - Barcelona, Spain
Istituto Clinico Humanitas
🇮🇹Rozzano (milano), Italy
Churchill Hospital
🇬🇧Oxford, Oxfordshire, United Kingdom
University Of Rochester
🇺🇸Rochester, New York, United States