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

Primary Purpose

Relapsed Hodgkin Lymphoma, Refractory Hodgkin Lymphoma

Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Nivolumab
Pembrolizumab
Sponsored by
UNC Lineberger Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed Hodgkin Lymphoma focused on measuring Classic Hodgkin Lymphoma, Relapsed Hodgkin Lymphoma, Refractory Hodgkin Lymphoma, Relapsed/Refractory Hodgkin Lymphoma, CD30, cell therapy, CAR-T, modified T cells, PD-1

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Lineberger Comprehensive Cancer Center at University of North CarolinaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm 1: Relapse After Prior CD30 CAR-T Therapy

Arm 2: Relapse with no Prior CD30 CAR-T Therapy

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
September 13, 2019
Last Updated
February 21, 2023
Sponsor
UNC Lineberger Comprehensive Cancer Center
Collaborators
American Society of Clinical Oncology
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1. Study Identification

Unique Protocol Identification Number
NCT04134325
Brief Title
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

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 1, 2019 (Actual)
Primary Completion Date
April 22, 2024 (Anticipated)
Study Completion Date
July 7, 2037 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UNC Lineberger Comprehensive Cancer Center
Collaborators
American Society of Clinical Oncology

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm 1: Relapse After Prior CD30 CAR-T Therapy
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm 2: Relapse with no Prior CD30 CAR-T Therapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
Opdivo
Intervention Description
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
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda
Intervention Description
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
Primary Outcome Measure Information:
Title
Objective response, defined as complete response (CR) or partial response (PR) at 12 weeks after initiating anti-PD-1 therapy
Description
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).
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Peripheral T-cell receptor frequency per 100,000 clones on Day 1, Day 21, and Day 42 of anti-PD-1 therapy.
Description
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.
Time Frame
42 days
Title
Percent change in peripheral blood T-cell subsets
Description
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.
Time Frame
42 days
Title
Progression free survival
Description
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.
Time Frame
From first day of anti-PD-1 therapy to clinical progression or death, up to 15 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Catherine Cheng
Phone
919-445-4208
Email
catherine_cheng@med.unc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Caroline Babinec
Phone
919-962-7426
Email
caroline_babinec@med.unc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Natalie Grover, MD
Organizational Affiliation
UNC Lineberger Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lineberger Comprehensive Cancer Center at University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Catherine Cheng
Phone
919-445-4208
Email
catherine_cheng@med.unc.edu
First Name & Middle Initial & Last Name & Degree
Caroline Babinec
Phone
919-962-7426
Email
caroline_babinec@med.unc.edu

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://unclineberger.org/
Description
UNC Lineberger Comprehensive Cancer Center

Learn more about this trial

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

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