Study of PD-1 Inhibitors After CD30.CAR T Cell Therapy in Relapsed/Refractory Hodgkin Lymphoma
- Conditions
- Relapsed Hodgkin LymphomaRefractory Hodgkin Lymphoma
- Interventions
- Registration Number
- NCT04134325
- Lead Sponsor
- UNC Lineberger Comprehensive Cancer Center
- Brief Summary
LCCC1852-ATL is a prospective 2-arm study designed to determine if chimeric antigen receptor T (CAR-T) cells result in immunomodulation which can be subsequently exploited by programmed cell death protein 1 (PD-1) antibodies to achieve clinical responses in subjects with relapsed/refractory (r/r) classical Hodgkin Lymphoma (cHL).
- Detailed Description
In this study, investigators will enroll subjects with relapsed/refractory cHL being treated with anti-PD-1 therapy. The study will examine the treatment of relapsed/refractory cHL in this population in , two arms with 10 subjects each: (1) Arm 1: 10 subjects who have previously received anti-PD-1 therapy and experienced progression and more recently received CD30 CAR-T cell therapy and have evidence of progression, and (2) Arm 2 : 10 subjects who have never received CD30 CAR-T therapy and have evidence of progression are initiating treatment with anti-PD1 therapy. In both arms of the study subjects will be offered anti-PD-1 therapy (nivolumab or pembrolizumab, at the discretion of treating oncologist), as per standard of care in r/r cHL
The primary objective of this study is to estimate the objective response rate (ORR) of anti-PD-1 therapy after progression on CD30 CAR-T cell therapy in study Arm 1 subjects within r/r cHL. The secondary objectives will be to measure the change in T-cell receptor clonality during treatment with anti-PD-1 therapy after progression after CD30 CAR-T therapy in these subjects, the change in peripheral blood immunophenotype during treatment with anti-PD-1 therapy after progression on CD30 CAR-T cell therapy and progression free survival (PFS) of anti-PD-1 therapy after progression on CD30 CAR-T cell therapy.
Preliminary data from subjects treated with anti-PD-1 therapy after progression following CD30 CAR-T cell therapy has suggested surprisingly robust clinical responses to anti-PD-1 therapy. Therefore, this study is an important advancement for understanding both immunomodulation after CD30 CAR-T cell therapy, as well as clinical response to anti-PD-1 therapy. This study will serve as a baseline for clinical response and immunomodulation for future clinical trials evaluating the combination of anti-PD-1 therapy and CD30 CAR-T cell therapy.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 10
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1: Relapse After Prior CD30 CAR-T Therapy Pembrolizumab Subjects with relapsed/refractory classical Hodgkin lymphoma (r/r cHL) who have previously progressed on anti-PD-1 therapy, have received a CD30 CAR-T cell therapy and have evidence of progression. Subjects will be offered anti-PD-1 therapy (nivolumab or pembrolizumab, at the discretion of treating oncologist), as per standard of care in r/r cHL. Arm 1: Relapse After Prior CD30 CAR-T Therapy Nivolumab Subjects with relapsed/refractory classical Hodgkin lymphoma (r/r cHL) who have previously progressed on anti-PD-1 therapy, have received a CD30 CAR-T cell therapy and have evidence of progression. Subjects will be offered anti-PD-1 therapy (nivolumab or pembrolizumab, at the discretion of treating oncologist), as per standard of care in r/r cHL. Arm 2: Relapse with no Prior CD30 CAR-T Therapy Nivolumab Subjects with relapsed/refractory classical Hodgkin lymphoma (r/r cHL) who have previously progressed on anti-PD-1 therapy, have not received a CD30 CAR-T cell therapy and have evidence of progression. Subjects will be offered anti-PD-1 therapy (nivolumab or pembrolizumab, at the discretion of treating oncologist), as per standard of care in r/r cHL. Arm 2: Relapse with no Prior CD30 CAR-T Therapy Pembrolizumab Subjects with relapsed/refractory classical Hodgkin lymphoma (r/r cHL) who have previously progressed on anti-PD-1 therapy, have not received a CD30 CAR-T cell therapy and have evidence of progression. Subjects will be offered anti-PD-1 therapy (nivolumab or pembrolizumab, at the discretion of treating oncologist), as per standard of care in r/r cHL.
- Primary Outcome Measures
Name Time Method Objective response, defined as complete response (CR) or partial response (PR) at 12 weeks after initiating anti-PD-1 therapy 12 weeks Response will be determined by the Lymphoma Response to Immunomodulatory Therapy Criteria in order to evaluate the efficacy of anti-PD-1 therapy after progression on CD30 CAR-T cell therapy in relapsed/refractory (r/r) classical Hodgkin Lymphoma (cHL).
- Secondary Outcome Measures
Name Time Method Progression free survival From first day of anti-PD-1 therapy to clinical progression or death, up to 15 years Progression free survival of anti-PD-1 therapy after progression on CD30 CAR-T cell therapy will be defined as the duration of time from the first day of anti-PD-1 therapy to clinical progression or death as a result of any cause. Response will be determined by the Lymphoma Response to Immunomodulatory Therapy Criteria.
Peripheral T-cell receptor frequency per 100,000 clones on Day 1, Day 21, and Day 42 of anti-PD-1 therapy. 42 days To measure the change in peripheral blood T-cell receptor clonality during treatment with anti-PD-1 therapy after progression on CD30 CAR-T cell therapy.
Percent change in peripheral blood T-cell subsets 42 days Percent change in peripheral blood T-cell subsets will be measured by Fluidigm® based mass cytometry from Day 1 of anti-PD-1 therapy to Day 21 and Day 42 of anti-PD-1 therapy.
Trial Locations
- Locations (1)
Lineberger Comprehensive Cancer Center at University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States