Clinical trial NCT04134325: Study of PD-1 Inhibitors After CD30.CAR T Cell Therapy in Relapsed/Refractory Hodgkin Lymphoma
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: EARLY_PHASE1
Conditions: Relapsed Hodgkin Lymphoma
Refractory Hodgkin Lymphoma
Keywords: Classic Hodgkin Lymphoma
Relapsed Hodgkin Lymphoma
Refractory Hodgkin Lymphoma
Relapsed/Refractory Hodgkin Lymphoma
CD30
cell therapy
CAR-T
modified T cells
PD-1
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: American Society of Clinical Oncology
First posted: 2019-10-22
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Objective response, defined as complete response (CR) or partial response (PR) at 12 weeks after initiating anti-PD-1 therapy
timeFrame: 12 weeks
Secondary outcomes:
measure: Peripheral T-cell receptor frequency per 100,000 clones on Day 1, Day 21, and Day 42 of anti-PD-1 therapy.
timeFrame: 42 days
measure: Percent change in peripheral blood T-cell subsets
timeFrame: 42 days
measure: Progression free survival
timeFrame: From first day of anti-PD-1 therapy to clinical progression or death, up to 15 years
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina
state: North Carolina
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Natalie Grover, MD
role: PRINCIPAL_INVESTIGATOR
References: