Study of PD-1 Inhibitors After CD30.CAR T Cell Therapy in Relapsed/Refractory Hodgkin Lymphoma
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm 1: Relapse After Prior CD30 CAR-T Therapy 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. |
Biological: Nivolumab
Nivolumab administered at 240mg every two weeks or 480 mg every four weeks as per standard of care after treatment with CD30.CAR T cells
Other Names:
Biological: Pembrolizumab
Pembrolizumab administered at 200 mg every three weeks or 400 mg every six weeks as per standard of care after treatment with CD30.CAR T cells
Other Names:
|
| Experimental: Arm 2: Relapse with no Prior CD30 CAR-T Therapy 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. |
Biological: Nivolumab
Nivolumab administered at 240mg every two weeks or 480 mg every four weeks as per standard of care after treatment with CD30.CAR T cells
Other Names:
Biological: Pembrolizumab
Pembrolizumab administered at 200 mg every three weeks or 400 mg every six weeks as per standard of care after treatment with CD30.CAR T cells
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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.
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria for Arm 1: Relapse After Prior CD 30 CAR-T Therapy
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Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
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Age ≥18 years at the time of consent.
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Subject is planned to start on standard of care anti-PD-1 therapy per community standards of medical care by their treating oncologist.
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Subject has a diagnosis of relapsed/refractory classical Hodgkin lymphoma after at least three lines of prior therapy with clinical progression after either ATLCAR.CD30 and/or ATLCAR.CD30.CCR4. The CAR-T cell product may be either the UNC, Baylor or Tessa product.
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Subjects with prior allogeneic stem cell transplant will be eligible but will be counseled during consent regarding possible increased risk of graft versus host disease with anti-PD-1 therapy after allogeneic stem cell transplant.
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Subjects must have previously been treated with anti-PD-1 therapy (any anti-PD-1 therapy either standard of care or investigational) prior to receiving autologous CAR-T-cell therapy.
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Subject is willing to provide blood samples that are clinically necessary during anti-PD-1 therapy administered per community standards of medical care.
Inclusion Criteria for Arm 2: Relapse with no Prior CD 30 CAR-T Therapy
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Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
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Age ≥18 years at the time of consent.
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Subject is planned to start on standard of care anti-PD-1 therapy per community standards of medical care by their treating oncologist.
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Subject has a diagnosis of classical Hodgkin lymphoma.
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Subjects with prior allogeneic stem cell transplant will be eligible but will be counseled during consent regarding possible increased risk of graft versus host disease with anti-PD-1 therapy after allogeneic stem cell transplant.
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Subject is willing to provide blood samples that are clinically necessary during anti-PD-1 therapy administered per community standards of medical care.
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Subject is willing and able to comply with study procedures based on the judgment of the investigator or protocol designee.
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Subject is willing to consent to study-required blood draws.
Exclusion Criteria for Arm 1: Relapse After Prior CD 30 CAR-T Therapy
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Subject has received anti-CD30 CAR-T therapy within the previous 6 weeks.
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Subject has known active infection with HIV, HTLV, HBV, HCV or any active, uncontrolled infection or sepsis.
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Subject has received chemotherapy or anti-PD-1 therapy following CD30 CAR-T cell product administration.
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Subject has a known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least five years.
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Subject is currently using systemic corticosteroids at doses ≥10 mg prednisone daily or its equivalent, or other immunosuppressive medications.
Exclusion Criteria for Arm 2: Relapse with no Prior CD 30 CAR-T Therapy
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Subject has received anti-CD30 CAR-T therapy
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Subject is currently using systemic corticosteroids at doses ≥10 mg prednisone daily or its equivalent, or other immunosuppressive medications.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Lineberger Comprehensive Cancer Center at University of North Carolina | Chapel Hill | North Carolina | United States | 27599 |
Sponsors and Collaborators
- UNC Lineberger Comprehensive Cancer Center
- American Society of Clinical Oncology
Investigators
- Principal Investigator: Natalie Grover, MD, UNC Lineberger Comprehensive Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- LCCC1852-ATL