Hodgkin Lymphoma With no Available Curative Treatment Options Who Have a Limited Prognosis
Conditions
Brief summary
Pilot open-label study to estimate the feasibility, safety and efficacy of intravenously administered, RNA electroporated autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCR and 4-1BB (TCR /4-1BB) costimulatory domains (referred to as RNA CART19) in Hodgkin Lymphoma (HL) patients.
Interventions
BIOLOGICALRNA anti-CD19 CAR T cells
intravenously administered, RNA electroporated autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCR /4-1BB) costimulatory domains (referred to as RNA CART19)
Sponsors
University of Pennsylvania
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female subjects with HL with no available curative treatment options (such as autologous SCT) who have a limited prognosis (several months to \< 2 year survival) with currently available therapies will be enrolled. i. HL with biopsy-proven relapse or refractory disease who are unresponsive to or intolerant of at least one line of standard salvage therapy ii. Patients must have evaluable disease by radiologic imaging (FDG PET/CT or PET/MRI) within 42 days of enrollment; evaluable includes both assessable and/or measurable disease as defined by Cheson et al., 2007. * Age ≥ 18 years of age * Creatinine \< 1.6 mg/dl. * ALT/AST \< 3x upper limit of normal * Bilirubin \< 2.0 mg/dl, unless subject has Gilbert's syndrome (≤3.0 mg/dL) * Patients with relapsed disease after prior allogeneic SCT (myeloablative or non-myeloablative) will be eligible if they meet all other inclusion criteria and 1. Have no active GVHD and require no immunosuppression 2. Are more than 6 months from transplant * Performance status (ECOG) 0 or 1. * Left Ventricular Ejection Fraction (LVEF) ≥ 40% as confirmed by ECHO/MUGA * Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen \> 92% on room air * Written informed consent is given. * Successful T cell test expansion (to be performed as part of inclusion criteria until 3 subjects meet all enrollment criteria)
Exclusion criteria
* Pregnant or lactating women. The safety of this therapy on unborn children is not known. Female study participants of reproductive potential must have a negative serum pregnancy test at enrollment. A urine or serum pregnancy test will be performed within 72 hours before the first RNA CART19 infusion. * Uncontrolled active infection. * Active hepatitis B or hepatitis C infection. * Any uncontrolled active medical disorder that would preclude participation as outlined. * HIV infection. * Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system * Patients with active CNS involvement by malignancy. Patients with prior CNS disease that has been effectively treated will be eligible providing treatment was \>4 weeks before enrollment * Patients in complete remission with no evidence of evaluable disease by radiologic imaging. * History of allergy to murine proteins. * History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40). * Anti-CD20 monoclonal antibody therapy within the last 3 months, or absence of circulating B cells. * Class III/IV cardiovascular disability according to the New York Heart Association Classification (see Appendix 1).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Adverse Events | 2 years |
Countries
United States
Outcome results
None listed