Clinical Trials /

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

NCT04134325

Description:

LCCC1852-ATL is a prospective pilot 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).

Related Conditions:
  • Classical Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: LCCC1852-ATL
  • NCT ID: NCT04134325

Conditions

  • Relapsed Hodgkin Lymphoma
  • Refractory Hodgkin Lymphoma

Interventions

DrugSynonymsArms
NivolumabOpdivoSingle Arm PD-1 Inhibitors after CD30.CAR-T Therapy
PembrolizumabKeytrudaSingle Arm PD-1 Inhibitors after CD30.CAR-T Therapy

Purpose

LCCC1852-ATL is a prospective pilot 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 10 subjects with relapsed/refractory 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 HL.
      Peripheral blood samples will be collected from subjects after consent has been obtained at
      the time of progression following CD30 CAR-T cell therapy as well as at Day 21 and Day 42 of
      anti-PD-1 therapy. Investigators will also have access to peripheral blood samples prior to
      CD30 CAR-T cell therapy, acquired during a prior clinical study. Peripheral blood samples
      will be immunophenotyped by mass cytometry and T-cell receptor (TCR) sequencing will be
      pursued to establish expansion of clinically relevant T-cell clones.

      The primary objective of this study is to measure the ability of anti-PD-1 therapy to rescue
      peripheral T-cell exhaustion after progression following CD30 CAR-T cell therapy. The
      secondary objectives will be to measure the immunomodulatory effect of CD30 CAR-T cell
      therapy as well as estimate the objective response rate (ORR) 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 pilot study is an important advancement in our understanding of 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.
    

Trial Arms

NameTypeDescriptionInterventions
Single Arm PD-1 Inhibitors after CD30.CAR-T TherapyExperimentalSubjects 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.
  • Nivolumab
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  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.

          -  Subjects must have previously been treated with anti-PD-1 therapy 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.

          -  Female subject of childbearing potential must agree to use adequate contraception
             during the study. Adequate contraception is defined by the concomitant use of two
             effective methods of contraception from the time of informed consent until 150 days
             after treatment discontinuation. The two contraception methods can be comprised of two
             barrier methods, or a barrier method plus a hormonal method or an intrauterine device
             that meets <1% failure rate for protection from pregnancy in the product label. Female
             subjects of non-childbearing potential are those who are postmenopausal greater than 1
             year or who have had a bilateral tubal ligation or hysterectomy or bilateral
             oophorectomy. Female subjects must refrain from egg cell donation while on study
             treatment and for at least 150 days after the last dose of investigational product.

          -  Male subjects with female partners must have had a prior vasectomy or agree to use an
             adequate method of contraception (i.e., double barrier method: condom plus spermicidal
             agent) starting with the first dose of study therapy through 150 days after the last
             dose of study therapy. Male subjects should agree to refrain from sperm donation while
             receiving study treatment and for at least 150 days after the last dose of study
             treatment.

          -  Subjects is willing and able to comply with study procedures based on the judgement of
             the investigator or protocol designee.

          -  Subject is willing to consent to study-required blood draws.

        Exclusion Criteria:

          -  Subject has history of hypersensitivity reactions to anti-PD-1 therapy.

          -  Subject has any contraindication to anti-PD-1 therapy at time of enrollment or
             inability to be treated with anti-PD-1 therapy for any other reason.

          -  Subject has active autoimmune disease that has required systemic treatment in the past
             2 years (i.e. with use of disease modifying agents, corticosteroids or
             immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or
             physiologic corticosteroids replacement therapy for adrenal or pituitary
             insufficiency, etc.) is not considered a form of systemic replacement.

          -  Subject has evidence of interstitial lung disease or a history of (non-infectious)
             pneumonitis that required steroids or current pneumonitis. History of radiation
             pneumonitis is not considered a form of non-infectious pneumonitis of concern.

          -  Subject has received anti-CD30 CAR-T therapy within the previous 6 weeks.

          -  Subject is pregnant or breastfeeding (Note: breast milk cannot be stored for future
             use while the mother is being treated on the study. Subject must abstain from
             breastfeeding for 150 days after end of study).

          -  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.

          -  Subject has received a live attenuated vaccine within 30 days of initiating study
             treatment (i.e., 30 days prior to the first dose, during treatment, and for 30 days
             after study treatment discontinuation). Inactivated vaccines, such as the injectable
             influenza vaccine, are permitted.

          -  Subject has received radiation therapy less than 7 days prior to anti-PD-1 therapy
             initiation

          -  Subject has had a major surgery within 28 days prior to anti-PD-1 therapy.

          -  Subject is not considered to be an acceptable candidate for anti-PD-1 therapy per the
             treating oncologist's discretion.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Presence of immunomodulatory (T-cell receptor) TCR response with anti-PD-1 therapy after progression on CD30 CAR-T cell therapy.
Time Frame:42 days
Safety Issue:
Description:Change in peripheral immunophenotyped by mass cytometry and TCR clonal expansion comparing peripheral blood samples prior to anti-PD-1 therapy to samples at day 21 and day 42 of anti-PD-1 therapy. The presence of immunomodulatory TCR response would suggest rescue of peripheral T-cell exhaustion.

Secondary Outcome Measures

Measure:Immunomodulatory effect of CD30 CAR-T cell therapy on peripheral blood immunophenotypes
Time Frame:As early as 6 weeks after CD30 CAR-T cell therapy
Safety Issue:
Description:The change in peripheral immunophenotyped by mass cytometry comparing peripheral blood samples before CD30 CAR-T cell therapy and at the time of clinical progression.
Measure:Immunomodulatory effect of CD30 CAR-T cell therapy on peripheral blood TCR clonality
Time Frame:As early as 6 weeks after CD30 CAR-T cell therapy
Safety Issue:
Description:The change in TCR clonality comparing peripheral blood samples before CD30 CAR-T cell therapy and at the time of clinical progression.
Measure:Objective response rate of anti-PD-1 therapy after progression on CD30 CAR-T cell therapy.
Time Frame:12 weeks
Safety Issue:
Description:The objective response rate will be defined as the rate of complete responses (CR) + partial responses (PR) at 12 weeks after initiating anti-PD-1 therapy. Response will be determined by the Lymphoma Response to Immunomodulatory Therapy Criteria.
Measure:Progression free survival of anti-PD-1 therapy after progression on CD30 CAR-T cell therapy.
Time Frame:From first day of anti-PD-1 therapy to clinical progression or death, up to 15 years
Safety Issue:
Description:Progression free survival 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.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:UNC Lineberger Comprehensive Cancer Center

Trial Keywords

  • Classic Hodgkin Lymphoma
  • Relapsed Hodgkin Lymphoma
  • Refractory Hodgkin Lymphoma
  • Relapsed/Refractory Hodgkin Lymphoma
  • CD30
  • cell therapy
  • CAR-T
  • modified T cells

Last Updated

October 17, 2019