Expired Study
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Philadelphia, Pennsylvania 19104


Purpose:

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.


Study summary:

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.


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.


Study is Available At:


Original ID:

14BT055, 821157


NCT ID:

NCT02624258


Secondary ID:


Study Acronym:


Brief Title:

Pilot Study of Non-Viral, RNA-Redirected Autologous T Cells in Patients With Refractory or Relapsed Hodgkin Lymphoma


Official Title:

Pilot Study of Non-Viral, RNA-Redirected Autologous T Cells Engineered to Contain Anti-CD19 Linked to TCR and 4-1BB Signaling Domains in Patients With Refractory or Relapsed Hodgkin Lymphoma


Overall Status:

Active, not recruiting


Study Phase:

N/A


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

24 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

University of Pennsylvania


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

2


Enrollment Type:

Actual


Overall Contact Information

Official Name:Susan Rheingold, MD
Principal Investigator
Children's Hospital of Philadelphia

Study Dates

Start Date:November 2015
Completion Date:December 2020
Completion Type:Anticipated
Primary Completion Date:July 2020
Primary Completion Type:Anticipated
Verification Date:September 2019
Last Changed Date:September 10, 2019
First Received Date:December 1, 2015

Study Outcomes

Outcome Type:Primary Outcome
Measure:Incidence of Treatment-Emergent Adverse Events, defined as NCI CTCAE V4 > Grade 3
Time Frame:Month 4 post-CART19 Infusion
Safety Issues:False
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 infus

Study Interventions

Intervention Type:Biological
Name:CD19 RNA redirected autologous T-cells (RNA CART19
Description: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.
Arm Name:RNA CART19 cells

Study Arms

Study Arm Type:Experimental
Arm Name:RNA CART19 cells
Description:CD19 RNA redirected autologous T-cells (RNA CART19 cells)

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:University of Pennsylvania
Agency Class:Other
Agency Type:Collaborator
Agency Name:Children's Hospital of Philadelphia

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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