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.
Terminated
Early Phase 1
| Drug | Synonyms | Arms |
|---|---|---|
| CD19 RNA redirected autologous T-cells (RNA CART19 cells) | RNA CART19 cells |
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.
| Name | Type | Description | Interventions |
|---|---|---|---|
| RNA CART19 cells | Experimental | CD19 RNA redirected autologous T-cells (RNA CART19 cells) |
|
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.
| Maximum Eligible Age: | 24 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Incidence of Treatment-Emergent Adverse Events, defined as NCI CTCAE V4 > Grade 3 |
| Time Frame: | Month 4 post-CART19 Infusion |
| Safety Issue: | |
| Description: | 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. |
| Phase: | Early Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Terminated |
| Lead Sponsor: | University of Pennsylvania |
May 21, 2020
