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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Refractory Hodgkin Lymphoma; Relapsed Hodgkin Lymphoma
• Intervention / Treatment: Biological: Nivolumab; Biological: Pembrolizumab

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 Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Caroline Babinec; Phone Number: 919-962-7426; Email: Caroline_babinec@med.unc.edu
• Study Contact Backup: Name: Catherine Cheng; Phone Number: 919-445-4208; Email: catherine_cheng@med.unc.edu

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • Lineberger Comprehensive Cancer Center at University of North Carolina
      • Contact: Caroline Babinec; Phone Number: 919-962-7426; Email: Caroline_babinec@med.unc.edu
      • Contact: Catherine Cheng; Phone Number: 919-445-4208; Email: catherine_cheng@med.unc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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: 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 Names: Keytruda
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: 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 Names: Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborators: American Society of Clinical Oncology
• Investigators: Principal Investigator: Natalie Grover, MD, UNC Lineberger Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• UNC Lineberger Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2019
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): July 7, 2037

Study Registration Dates

• First Submitted: September 13, 2019
• First Submitted That Met QC Criteria: October 17, 2019
• First Posted (Actual): October 22, 2019

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: CAR-T; cell therapy; PD-1; Refractory Hodgkin Lymphoma; CD30; modified T cells; Relapsed/Refractory Hodgkin Lymphoma; Classic Hodgkin Lymphoma; Relapsed Hodgkin Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Pembrolizumab
• Other Study ID Numbers: LCCC1852-ATL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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