pilot study of non-viral, rna-redirected autologous t cells in patients with refractory or relapsed hodgkin lymphoma

Conditions: Hodgkin Lymphoma

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 tcrζ and 4-1bb (tcrζ /4-1bb) costimulatory domains (referred to as "rna cart19") in hodgkin lymphoma (hl) patients. subjects will be treated with iv administration of rna anti-cd19 car t cells for a total of six doses over 3 weeks.

the study will enroll 10 evaluable patients. evaluable patients are those who have received at least 1 of the 6 rna cart19 doses at the protocol-specified level. important safety data can be collected even if a patient receives only one rna cart19 dose. subjects (n = 10) will receive up to six iv doses of 8x105-1.5x106 rna cart19 cells/kg/dose for subjects\<80kg and 1x108 rna cart19 cells/dose (±20%) for subjects ≥80kg. the rna cart19 doses and mid-treatment single dose cyclophosphamide will be administered on mondays, wednesdays or fridays. dosing can be initiated on any of those days. subjects will be infused in a staggered fashion at two week intervals; that is, the next subject cannot be infused prior to two weeks since the last infusion of the previous subject.

Eligibility criteria:
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. * hl with biopsy-proven relapse or refractory disease who are unresponsive to or intolerant of at least one line of standard salvage therapy; * patients must have evaluable disease by radiologic imaging (fdg pet-ct or fdg pet-mri) within 42 day of enrollment; evaluable includes both assessable and/or measurable disease * age 18 to 24 years. patients ages 22-24 will only be enrolled if they are currently being treated at chop or another pediatric facility/oncologist. * expected survival \> 12 weeks at time of screening * adequate organ function defined as: * renal function defined as: * creatinine clearance or radioisotope gfr \> 60 ml/min/1.73 m2 or * serum creatinine: \< 1.7mg/dl (male subjects) or \< 1.4mg/dl (female subjects) * alt \< 5 times the uln for age * total bilirubin \< 2.0 mg/dl * must have a minimum level of pulmonary reserve defined as ≤ grade 1 dyspnea and pulse oxygenation \> 94% on room air * patients with relapsed disease after prior allogeneic sct (myeloablative or non-myeloablative) will be eligible if they meet all other inclusion criteria and * have no active gvhd and require no immunosuppression * are more than 6 months from transplant 6) karnofsky performance status ≥ 50 at screening * left ventricular shortening fraction (lvsf) \> 28% confirmed by echocardiogram, or left ventricular ejection fraction (lvef) \> 45% confirmed by echocardiogram or muga * signed written informed consent must be obtained prior to any study procedures * 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 pregnancy test will be performed within 48 hours before the 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 known 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 by radiologic imaging of disease. * 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 * unstable angina and/or myocardial infarction within 6 months prior to screening.