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

NCT ID: NCT02624258

Last Updated: 2020-05-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2019-12-06

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.

Conditions

Hodgkin Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RNA CART19 cells

CD19 RNA redirected autologous T-cells (RNA CART19 cells)

Group Type: EXPERIMENTAL

CD19 RNA redirected autologous T-cells (RNA CART19 cells)

Intervention Type: BIOLOGICAL

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.

Interventions

CD19 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.

Intervention Type: BIOLOGICAL

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
• 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

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 24 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Hospital of Philadelphia

OTHER

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Susan Rheingold, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Countries

United States

References

Svoboda J, Rheingold SR, Gill SI, Grupp SA, Lacey SF, Kulikovskaya I, Suhoski MM, Melenhorst JJ, Loudon B, Mato AR, Nasta SD, Landsburg DJ, Youngman MR, Levine BL, Porter DL, June CH, Schuster SJ. Nonviral RNA chimeric antigen receptor-modified T cells in patients with Hodgkin lymphoma. Blood. 2018 Sep 6;132(10):1022-1026. doi: 10.1182/blood-2018-03-837609. Epub 2018 Jun 20.

Reference Type: DERIVED

PMID: 29925499 (View on PubMed)

Other Identifiers

14BT055, 821157

Identifier Type: -

Identifier Source: org_study_id