Hodgkin Lymphoma
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 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.
Detailed description
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.
Interventions
BIOLOGICALCD19 RNA redirected autologous T-cells (RNA CART19 cells)
Subjects will be treated with IV administration of RNA anti-CD19 CAR T cells for a total of six doses over 3 weeks. The first dose will be administered 1-4 days after infusion of cyclophosphamide 30mg/kg.
Sponsors
Children's Hospital of Philadelphia
University of Pennsylvania
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 24 Years
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. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events, defined as NCI CTCAE V4 > Grade 3 | Month 4 post-CART19 Infusion | Occurrence of study related adverse events, defined as NCI CTCAE V4 \> grade 3 signs/symptoms, laboratory toxicities and clinical events that are possible, likely or definitely related to study treatment at any time from the first cyclophosphamide infusion until Month 4. |
Countries
United States
Outcome results
None listed