CD19 Redirected Autologous T Cells for Hodgkin Lymphoma

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

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 TCR and 4-1BB (TCR /4-1BB) costimulatory domains (referred to as RNA CART19) in Hodgkin Lymphoma (HL) patients.

Study Overview

• Status: Terminated
• Conditions: Hodgkin Lymphoma With no Available Curative Treatment Options Who Have a Limited Prognosis
• Intervention / Treatment: Biological: RNA anti-CD19 CAR T cells

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center of the University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

  i. HL with biopsy-proven relapse or refractory disease who are unresponsive to or intolerant of at least one line of standard salvage therapy ii. Patients must have evaluable disease by radiologic imaging (FDG PET/CT or PET/MRI) within 42 days of enrollment; evaluable includes both assessable and/or measurable disease as defined by Cheson et al., 2007.

• Age ≥ 18 years of age
• Creatinine < 1.6 mg/dl.
• ALT/AST < 3x upper limit of normal
• Bilirubin < 2.0 mg/dl, unless subject has Gilbert's syndrome (≤3.0 mg/dL)

• Patients with relapsed disease after prior allogeneic SCT (myeloablative or non-myeloablative) will be eligible if they meet all other inclusion criteria and

  1. Have no active GVHD and require no immunosuppression
  2. Are more than 6 months from transplant
• Performance status (ECOG) 0 or 1.
• Left Ventricular Ejection Fraction (LVEF) ≥ 40% as confirmed by ECHO/MUGA
• Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen > 92% on room air
• Written informed consent is given.
• 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 or serum pregnancy test will be performed within 72 hours before the first 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 a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system
• Patients with 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 of evaluable disease by radiologic imaging.
• 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.
• Class III/IV cardiovascular disability according to the New York Heart Association Classification (see Appendix 1).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RNA autologous T cells (anti CD19 CAR T cells)	Biological: RNA anti-CD19 CAR T cells; intravenously administered, RNA electroporated autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCR /4-1BB) costimulatory domains (referred to as RNA CART19)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Adverse Events	2 years

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Jakub Svoboda, MD, Abramson Cancer Center at Penn Medicine

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): June 27, 2017

Study Registration Dates

• First Submitted: October 27, 2014
• First Submitted That Met QC Criteria: October 27, 2014
• First Posted (Estimated): October 29, 2014

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 20, 2023
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease
• Other Study ID Numbers: UPCC 04414, 820840