Study of PD-1 Inhibitors After CD30.CAR T Cell Therapy in Relapsed/Refractory Hodgkin Lymphoma
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| ClinicalTrials.gov Identifier: NCT04134325 |
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Recruitment Status :
Recruiting
First Posted : October 22, 2019
Last Update Posted : May 27, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Relapsed Hodgkin Lymphoma Refractory Hodgkin Lymphoma | Biological: Nivolumab Biological: Pembrolizumab | Early Phase 1 |
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 Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 20 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Prospective Pilot Study Assessing the Immunomodulatory Effect and Clinical Activity of Programmed Cell Death Protein 1 Inhibition Following CD30 Directed Chimeric Antigen Receptor T Cell Therapy in Relapsed/Refractory Classical Hodgkin Lymphoma |
| Actual Study Start Date : | September 1, 2019 |
| Estimated Primary Completion Date : | July 7, 2022 |
| Estimated Study Completion Date : | July 7, 2037 |
| Arm | Intervention/treatment |
|---|---|
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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.
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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 Name: Opdivo 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 Name: Keytruda |
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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.
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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 Name: Opdivo 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 Name: Keytruda |
- Objective response, defined as complete response (CR) or partial response (PR) at 12 weeks after initiating anti-PD-1 therapy [ Time Frame: 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).
- Peripheral T-cell receptor frequency per 100,000 clones on Day 1, Day 21, and Day 42 of anti-PD-1 therapy. [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria for Arm 1: Relapse After Prior CD 30 CAR-T Therapy
- Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
- Age ≥18 years at the time of consent.
- Subject is planned to start on standard of care anti-PD-1 therapy per community standards of medical care by their treating oncologist.
- 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.
- 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.
- 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.
- 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
- Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
- Age ≥18 years at the time of consent.
- Subject is planned to start on standard of care anti-PD-1 therapy per community standards of medical care by their treating oncologist.
- Subject has a diagnosis of classical Hodgkin lymphoma.
- 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.
- Subject is willing to provide blood samples that are clinically necessary during anti-PD-1 therapy administered per community standards of medical care.
- Subject is willing and able to comply with study procedures based on the judgment of the investigator or protocol designee.
- Subject is willing to consent to study-required blood draws.
Exclusion Criteria for Arm 1: Relapse After Prior CD 30 CAR-T Therapy
- Subject has received anti-CD30 CAR-T therapy within the previous 6 weeks.
- Subject has known active infection with HIV, HTLV, HBV, HCV or any active, uncontrolled infection or sepsis.
- Subject has received chemotherapy or anti-PD-1 therapy following CD30 CAR-T cell product administration.
- 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.
- 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
- Subject has received anti-CD30 CAR-T therapy
- Subject is currently using systemic corticosteroids at doses ≥10 mg prednisone daily or its equivalent, or other immunosuppressive medications.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04134325
| Contact: Catherine Cheng | 919-445-4208 | catherine_cheng@med.unc.edu | |
| Contact: Caroline Babinec | 919-962-7426 | caroline_babinec@med.unc.edu |
| United States, North Carolina | |
| Lineberger Comprehensive Cancer Center at University of North Carolina | Recruiting |
| Chapel Hill, North Carolina, United States, 27599 | |
| Contact: Catherine Cheng 919-445-4208 catherine_cheng@med.unc.edu | |
| Contact: Caroline Babinec 919-962-7426 caroline_babinec@med.unc.edu | |
| Principal Investigator: | Natalie Grover, MD | UNC Lineberger Comprehensive Cancer Center |
| Responsible Party: | UNC Lineberger Comprehensive Cancer Center |
| ClinicalTrials.gov Identifier: | NCT04134325 |
| Other Study ID Numbers: |
LCCC1852-ATL |
| First Posted: | October 22, 2019 Key Record Dates |
| Last Update Posted: | May 27, 2022 |
| Last Verified: | May 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
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Classic Hodgkin Lymphoma Relapsed Hodgkin Lymphoma Refractory Hodgkin Lymphoma Relapsed/Refractory Hodgkin Lymphoma CD30 |
cell therapy CAR-T modified T cells PD-1 |
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Lymphoma Hodgkin Disease Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders |
Immune System Diseases Pembrolizumab Nivolumab Antineoplastic Agents, Immunological Antineoplastic Agents Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action |