Genetically Engineered Cells (ATLCAR.CD30 T Cells) for the Treatment of Relapsed or Refractory CD30 Positive Peripheral T Cell Lymphoma
- Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information explained to, understood by and signed by the subject or legally authorized representative
- Karnofsky score of > 60%
- Histological or cytological evidence/confirmation of CD30+ peripheral T-cell lymphoma per the 2017 World Health Organization Classification of Hematopoietic and Lymphoid Tissues
- CD30+ disease determined by biopsy after the subject’s most recent anti-CD30 therapy prior to ATLCAR.CD30 (result can be pending at the time of cell procurement, but must be confirmed prior to treatment with the first infusion of ATLCAR.CD30 cells). NOTE: CD30+ disease requires documented CD30 expression by immunohistochemistry based on the institutional hematopathology standard
- Subjects must have received at least two prior lines of therapy for their lymphoma. If transplant is given as a preplanned consolidation in first remission, it will not be counted as a second line of therapy
- Subjects relapsed after autologous or allogeneic stem cell transplant are eligible for this study
- Subjects relapsed after allogeneic stem cell transplantation are eligible provided the patient is >= 180 days from transplant, not on immunosuppressive therapy to treat/prevent graft-versus-host disease, and has no evidence of active graft versus-host disease
- Female subjects of childbearing potential must have a negative serum pregnancy test within 72 hours prior to cell procurement. Note: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided
- Female subjects of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 6 months after study 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. Women of childbearing potential will also be instructed to tell their male partners to use a condom
- Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee
- Subject is pregnant or lactating (Note: Breast milk cannot be stored for future use while the mother is being treated on study)
- 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
- Subjects diagnosed with cutaneous T-cell lymphoma including mycoides fungoides, Sezary syndrome, or any other variant of cutaneous T-cell lymphoma
- Current use of systemic corticosteroids at doses >= 10 mg prednisone daily or its equivalent; those receiving < 10 mg daily may be enrolled at discretion of investigator. Inhaled steroids are allowed
- Active infection with human immunodeficiency virus (HIV), human T-cell leukemia virus (HTLV), hepatitis C virus (HCV) (tests can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells). Note: To meet eligibility subjects are required to be negative for HIV antibody and HIV viral load, negative for HTLV1 and 2 antibody or polymerase chain reaction (PCR) negative for HTLV1 and 2, negative for HCV antibody or HCV viral load
- Subjects who are positive for hepatitis B surface antigen (can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells) are excluded. Subjects who are hepatitis B surface antigen negative but hepatitis B core antibody positive must have their hepatitis B viral load checked. These subjects will be excluded if their viral load is positive at baseline. Subjects who are core antibody positive and viral load negative at baseline will be considered eligible
I. To estimate the median progression free survival (PFS) after administration of the CD30 CAR-expressing autologous CD30CAR-CD28-CD3zeta-expressing T-lymphocytes (ATLCAR.CD30) in subjects with relapsed/refractory CD30+ peripheral T cell lymphoma.
I. To determine the best overall response rate (BOR) mediated by the ATLCAR.CD30 product administered in subjects with relapsed/refractory CD30+ peripheral T cell lymphoma.
II. To determine the objective response rate (ORR) mediated by the first infusion of the ATLCAR.CD30 product administered in patients with relapsed/refractory CD30+ peripheral T cell lymphoma.
III. To determine the percentage of responses improved by the second infusion of the ATLCAR.CD30 product administered in subjects with relapsed/refractory CD30+ peripheral T cell lymphoma with either partial response or stable disease following the first infusion of ATLCAR.CD30.
IV. To determine the safety and tolerability of administering two sequential infusions of the ATLCAR.CD30 product in subjects with relapsed/refractory CD30+ peripheral T cell lymphoma.
V. To estimate the median overall survival (OS) after administration of the ATLCAR.CD30 administered to subjects with relapsed/refractory CD30+ peripheral T cell lymphoma.
VI. To measure and compare the expansion and persistence of ATLCAR.CD30 in peripheral blood when infused after a single infusion of ATLCAR.CD30 cells and after two infusions with ATLCAR.CD30 cells.
I. To measure and compare homeostatic cytokines and immunophenotypes in the peripheral blood after infusion with ATLCAR.CD30 with either bendamustine and fludarabine or cyclophosphamide and fludarabine lymphodepletion.
II. To measure and compare changes in the tumor microenvironment before and after ATLCAR.CD30 infusion.
III. To determine potential correlation between CAR T cell behavior and the integration location of CAR.CD30.
IV. To measure patient-reported symptoms at baseline and over time in subjects with relapsed/refractory CD30+ peripheral T cell lymphoma receiving ATLCAR.CD30.
Patients receive bendamustine intravenously (IV) over 1 hour daily and fludarabine over 30 minutes IV daily for 3 days, followed by ATLCAR.CD30 IV over 5-10 minutes 2-14 days later. After 8 weeks-6 months, patients then receive cyclophosphamide IV daily and fludarabine IV over 30 minutes daily for 3 days, followed by a second dose of ATLCAR.CD30 IV over 5-10 minutes 2-14 days later.
After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 4 years, and then annually for up to 10 years.
Trial Phase Phase II
Trial Type Treatment
UNC Lineberger Comprehensive Cancer Center
Anne Wood Beaven
- Primary ID LCCC1904-ATL
- Secondary IDs NCI-2019-06539
- Clinicaltrials.gov ID NCT04083495