Study of PD-1 Inhibitors After CD30.CAR T Cell Therapy in Relapsed/Refractory Hodgkin Lymphoma

Refractory Hodgkin Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04134325
• Other study ID #: LCCC1852-ATL
• Status: Recruiting
• Phase: Early Phase 1
• Start date: September 1, 2019
• Est. completion date: July 7, 2037

Study information

• Verified date: April 2024
• Source: UNC Lineberger Comprehensive Cancer Center
• Contact: Catherine Cheng
• Phone: 919-445-4208
• Email: UNCImmunotherapy[@]med.unc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: July 7, 2037
• Est. primary completion date: April 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hodgkin Disease
• Lymphoma
• Refractory Hodgkin Lymphoma
• Relapsed Hodgkin Lymphoma

Intervention

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
• 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

Locations

Country	Name	City	State
United States	Lineberger Comprehensive Cancer Center at University of North Carolina	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
UNC Lineberger Comprehensive Cancer Center	American Society of Clinical Oncology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response, defined as complete response (CR) or partial response (PR) at 12 weeks after initiating anti-PD-1 therapy	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).	12 weeks
Secondary	Peripheral T-cell receptor frequency per 100,000 clones on Day 1, Day 21, and Day 42 of anti-PD-1 therapy.	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.	42 days
Secondary	Percent change in peripheral blood T-cell subsets	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.	42 days
Secondary	Progression free survival	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.	From first day of anti-PD-1 therapy to clinical progression or death, up to 15 years

External Links

•   UNC Lineberger Comprehensive Cancer Center