TmCD19-IL18 in CD19+ Cancers

NCT05989204 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: UPCC 12423
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I, open-label dose finding study to assess the safety and feasibility, pharmacokinetics, and preliminary efficacy of TmCD19-IL18 CAR T cells in patients with CD19+ cancers. This study will take place in two parts: a Dose-Finding Phase to determine the maximum tolerate dose (MTD), followed by a Dose Expansion Phase. In the Dose-Finding Phase, dose levels will be evaluated using a 3+3 dose escalation design to determine the MTD. Cumulative safety experience and manufacturing feasibility data from the Dose-Finding Phase will then be used to identify the dose level that can be progressed into the Dose Expansion Phase.

Conditions

Non Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (3)

• Number of subjects with dose limiting toxicities (DLTs)

  28 days after TmCD19-IL18 CART T cell infusion

• Determination of maximum tolerated dose (MTD)

  28 days after TmCD19-IL18 CART T cell infusion

• Incidence of Adverse Events as assessed by CTCAE v5.0

  Up to 15 years

Secondary Outcomes (8)

• Percentage of manufacturing products that meet release criteria

  1 month

• Overall response rate (ORR)

  4 months

• Best overall response (BOR)

  12 months

• Duration of response (DOR)

  15 years

• Overall Survival (OS)

  15 years

Study Arms (5)

NHL Dose Level 1

EXPERIMENTAL

7x10\^6 TmCD19-IL18 cells administered as a single intravenous (IV) infusion

Biological: TmCD19-IL18

NHL Dose Level -1

EXPERIMENTAL

2x10\^6 TmCD19-IL18 cells administered as a single intravenous (IV) infusion

Biological: TmCD19-IL18

NHL Dose Level 2

EXPERIMENTAL

2x10\^7 TmCD19-IL18 cells administered as a single intravenous (IV) infusion

Biological: TmCD19-IL18

NHL Dose Level 3

EXPERIMENTAL

6x10\^7 TmCD19-IL18 cells administered as a single intravenous (IV) infusion

Biological: TmCD19-IL18

NHL Dose Level 1a

EXPERIMENTAL

5x10\^6 TmCD19-IL18 CAR T cells

Biological: TmCD19-IL18

Interventions

TmCD19-IL18 BIOLOGICAL

autologous Chimeric Antigen Receptor (CAR) T cells directed against the human CD19 antigen that also express human Interleukin 18 (IL-18)

NHL Dose Level -1; NHL Dose Level 1; NHL Dose Level 1a; NHL Dose Level 2; NHL Dose Level 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Active hepatitis B, active hepatitis C, or other active, uncontrolled infection.
• Class III/IV cardiovascular disability according to the New York Heart Association Classification.
• Clinically apparent arrhythmia or arrhythmias that are not stable on medical management within two weeks of physician-investigator confirmation of eligibility.
• Active acute or chronic GVHD requiring systemic therapy.
• Dependence on systemic steroids or immunosuppressant medications. For additional details regarding use of steroid and immunosuppressant medications.
• Receipt of prior huCART19-IL18 therapy.
• CNS disease as defined by disease-cohort as follows:
• a. Cohort A: Active CNS disease. Note: Patients with a history of CNS involvement that was successfully treated are eligible. A CNS evaluation is only required for eligibility if a subject is experiencing signs/symptoms of CNS involvement.
• Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods.
• Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, and unrelated to their cancer or previous cancer treatment.
• Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.

Sponsors & Collaborators

• University of Pennsylvania: lead
• Kite, A Gilead Company: collaborator

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Jakub Svoboda, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Abramson Cancer Center Clinical Trial Services

CONTACT

215-349-8245; PMCancerResearch@pennmedicine.upenn.edu

Jakub Svoboda, MD

CONTACT

Jakub.Svoboda@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 3+3 Dose escalation design

Study Record Dates

• First Submitted: August 2, 2023
• First Posted: August 14, 2023
• Study Start: November 13, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2041
• Last Updated: September 5, 2025

Record last verified: 2025-09

Locations

US (1)