study of pd-1 inhibitors after cd30.car t cell therapy in relapsed/refractory hodgkin lymphoma

Conditions: Relapsed Hodgkin Lymphoma; Refractory Hodgkin Lymphoma

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).

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.

Eligibility criteria:
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.

Keywords: classic hodgkin lymphoma relapsed hodgkin lymphoma refractory hodgkin lymphoma relapsed/refractory hodgkin lymphoma cd30 cell therapy car-t modified t cells pd-1