Phase 1 Clinical Trial of Intravesical Adoptive Cell Therapy {ACT) With Tumor Infiltrating Lymphocytes (TIL) for Patients With BCG Exposed High Grade Non-Muscle Invasive Bladder Cancer (NMIBC)

H. Lee Moffitt Cancer Center and Research Institute1 site in 1 country9 target enrollmentAugust 10, 2023

ConditionsUrothelial Carcinoma Non-Invasive Bladder Urothelial Carcinoma

InterventionsAdoptive Cell Therapy with Tumor-infiltrating Lymphocytes (TIL)

DrugsAdoptive Cell Therapy with Tumor-infiltrating Lymphocytes (TIL)

Overview

Phase: Phase 1
Intervention: Adoptive Cell Therapy with Tumor-infiltrating Lymphocytes (TIL)
Conditions: Urothelial Carcinoma
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Enrollment: 9
Locations: 1
Primary Endpoint: Safety of Adoptive Cell Therapy with TILs
Status: Active, not recruiting
Last Updated: 4 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of the study is to evaluate the feasibility, safety and tolerability of intravesical adoptive cell therapy using TIL (tumor infiltrating lymphocytes) in participants with urothelial cell carcinoma (UCC) non-muscle invasive bladder cancer (NMIBC).

Registry

clinicaltrials.gov

Start Date

August 10, 2023

End Date

January 1, 2027

Last Updated

4 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Bacillus Calmette-Guerin (BCG) exposed High Grade Non-Muscle Invasive Bladder Cancer (NMIBC) and healthy enough to participate:
•Histologically confirmed urothelial cell NMIBC (T1, Ta, and/or Tis) and: (a) bladder tumors with variant histology or mixed histology can be enrolled if the urothelial component is greater than 50% of the transurethral resection specimen (b) if Ta and T1, patients must have undergone complete restaging TURBT to confirm absence of muscle invasion (T2), however residual carcinoma in situ is acceptable. This restaging can be considered the primary tumor harvest if patients have had a previous resection.
•Have cytoscopic evidence of measurable disease. (There is no minimum measurement to be considered measurable disease. Any visible evidence is considered recurrence.)
•A tissue specimen may be obtained which is appropriate for TIL preparation. The tissue may be collected through a procedure the patient otherwise requires for treatment purposes. Alternatively, and in consultation with a surgical specialist, a separate procedure of limited risk to the patient (such as a repeat bladder biopsy) may be performed specifically for tissue collection purposes.
•ECOG performance status 0-1
•Participants must have adequate organ and marrow function in an assessment performed within 7 days (+ 3 day window) of enrollment as defined in protocol.
•Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

•Any previous treatment with intravesical chemotherapy within the previous 6 months.
•Current or prior use of any immunosuppressive medications, such as corticosteroids, within 14 days before enrollment. (a) Oral hydrocortisone, only for the purposes of a documented and confirmed adrenal insufficiency diagnosis, is permitted if ≤ 25 mg daily total dose. (b) Inhaled, intranasal, or topical corticosteroids are permitted.
•Current or prior use of anticancer therapy that has been shown to effect lymphocyte function before TIL collection.
•Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (other than stable atrial fibrillation).
•Patients known to be HIV positive, hepatitis B or C positive, or both rapid plasma reagin (RPR) and fluorescent treponemal antibody (FTA) positive. (Hepatitis B surface or core antibody alone is not indicative of Hepatitis B Virus (HBV) infection).
•Known history of previous tuberculosis
•Receipt of live attenuated vaccination within 30 days prior to first anticipated dose of TIL.
•History of allogeneic organ transplant
•History of primary immunodeficiency
•Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.

Arms & Interventions

Treatment with Adoptive Cell Therapy

TIL from bladder biopsies will be propagated and cultured with interleukin-2 (IL-2) to a target goal of \>30 million cells. These TIL then undergo rapid clonal expansion (REP) by incubation with anti-CD3 monoclonal antibody (mAb), resulting in \>500-fold expansion. After 4-6 weeks culture time intravesical TIL will be administered via intravesical infusion, consisting of up to 3.2e8 cells in 40 mL aliquot. Intravesical therapy will be administered for up to 2 hours. This treatment will occur four times (Day 0, Day 7, Day 14 and Day 21).

Intervention: Adoptive Cell Therapy with Tumor-infiltrating Lymphocytes (TIL)