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).
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
Drug | Synonyms | Arms |
---|
Nivolumab | Opdivo | Single Arm PD-1 Inhibitors after CD30.CAR-T Therapy |
Pembrolizumab | Keytruda | Single 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 been treated with 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 estimate the objective response rate (ORR) of
anti-PD-1 therapy after progression on CD30 CAR-T cell therapy in 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, 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 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
Name | Type | Description | Interventions |
---|
Single Arm PD-1 Inhibitors after CD30.CAR-T Therapy | Experimental | 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. | |
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 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 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.
- 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:
- 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 resulting from previous anti-PD-1 treatment 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 treatment).
- 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: | Objective response, defined as complete response (CR) or partial response (PR) at 12 weeks after initiating anti-PD-1 therapy |
Time Frame: | 12 weeks |
Safety Issue: | |
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). |
Secondary Outcome Measures
Measure: | Peripheral T-cell receptor frequency per 100,000 clones on Day 1, Day 21, and Day 42 of anti-PD-1 therapy. |
Time Frame: | 42 days |
Safety Issue: | |
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. |
Measure: | Percent change in peripheral blood T-cell subsets |
Time Frame: | 42 days |
Safety Issue: | |
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. |
Measure: | Progression free survival |
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 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. |
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
- PD-1
Last Updated
July 15, 2021