TmCD19-IL18 in CD19+ Cancers

NCT ID: NCT05989204

Last Updated: 2025-09-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-13
• Study Completion Date: 2041-10-01

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

NHL Dose Level 1

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

Group Type: EXPERIMENTAL

TmCD19-IL18

Intervention Type: 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

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

Group Type: EXPERIMENTAL

TmCD19-IL18

Intervention Type: 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 2

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

Group Type: EXPERIMENTAL

TmCD19-IL18

Intervention Type: 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 3

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

Group Type: EXPERIMENTAL

TmCD19-IL18

Intervention Type: 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 1a

5x10\^6 TmCD19-IL18 CAR T cells

Group Type: EXPERIMENTAL

TmCD19-IL18

Intervention Type: BIOLOGICAL

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

Interventions

TmCD19-IL18

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Relapsed/refractory disease after at least 2 prior lines of appropriate therapy; OR

2. Relapsed/refractory disease after autologous SCT; OR

3. Relapsed/refractory disease after allogeneic SCT.

ii. Follicular lymphoma

1. Patients must have either relapsed after, or be ineligible for, prior commercial CAR T cell therapy; AND

2. Received at least 2 prior lines of appropriate therapy (not including single agent monoclonal antibody therapy) and progressed within 2 years after second or higher line of therapy.

iii. Mantle cell lymphoma

1. Patients must have either failed standard of care CAR T cell therapy (e.g., Tecartus™, etc.) or other investigational CAR T cell product, OR be ineligible for standard of care Tecartus™; and

2. Patients must also meet one of the following criteria:

1. Relapsed/refractory disease after at least 2 prior lines of appropriate therapy, including a BTK inhibitor. Single-agent monoclonal antibody therapy does not count towards prior lines of therapy; OR

2. Relapsed/refractory disease after prior autologous SCT; OR

3. Relapsed/refractory disease after prior allogeneic SCT. iv. Marginal Zone Lymphoma

1. Patients must have received at least 2 prior lines of appropriate therapy which includes a BTK inhibitor (not including single agent monoclonal antibody therapy).

Exclusion Criteria

1. Active hepatitis B, active hepatitis C, or other active, uncontrolled infection.

2. Class III/IV cardiovascular disability according to the New York Heart Association Classification.

3. Clinically apparent arrhythmia or arrhythmias that are not stable on medical management within two weeks of physician-investigator confirmation of eligibility.

4. Active acute or chronic GVHD requiring systemic therapy.

5. Dependence on systemic steroids or immunosuppressant medications. For additional details regarding use of steroid and immunosuppressant medications.

6. Receipt of prior huCART19-IL18 therapy.

7. 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.

8. Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods.

9. 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.

10. Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.

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

Sponsors

Kite, A Gilead Company

INDUSTRY

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jakub Svoboda, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Abramson Cancer Center Clinical Trial Services

Role: CONTACT

PMCancerResearch@pennmedicine.upenn.edu

215-349-8245

Jakub Svoboda, MD

Role: CONTACT

Jakub.Svoboda@pennmedicine.upenn.edu

Facility Contacts

Abramson Cancer Center Clinical Trial Services

Role: primary

PMCancerResearch@pennmedicine.upenn.edu

215-349-8245

Other Identifiers

UPCC 12423

Identifier Type: -

Identifier Source: org_study_id