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Intravesical Adoptive Cell Therapy w/ TIL for BCG Exposed High Grade NMIBC

Primary Purpose

Urothelial Carcinoma, Non-Invasive Bladder Urothelial Carcinoma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Adoptive Cell Therapy with Tumor-infiltrating Lymphocytes (TIL)
Sponsored by
H. Lee Moffitt Cancer Center and Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Urothelial Carcinoma focused on measuring Bladder cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Screening 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. Patients with active systemic infections requiring intravenous antibiotics within 1 week prior to enrollment. Any unresolved toxicity (>CTCAE v5 grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripheral neuropathy). History of pneumonitis or drug-related inflammatory lung disease. Active or prior documented autoimmune disease within the past 2 years. Note: Subjects with vitiligo, Grave's disease, limited site eczema, or limited site plaque psoriasis not requiring systemic treatment (within the past 2 years), or other autoimmune conditions which are not expected to recur, are allowed after approval from the medical monitor or PI. Patients with other prior malignancies must have had a ≥ 2-year disease-free interval, except for: in situ carcinoma of the cervix, in situ ductal carcinoma of the breast, in situ prostate cancer, in situ bladder cancer. These must have been deemed stable and not expected to relapse. In addition, early stage skin cancers, including basal, squamous cell cutaneous carcinoma, and melanoma, are permitted if previously treated with curative intent and not expected to relapse. Women who are pregnant or lactating. The effects of adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) infusion on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and until 4 months after completion of study drug administration. Those who do not agree must be excluded. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. WOCBP are defined as premenopausal women capable of becoming pregnant. Penicillin allergy (Penicillin is used in the manufacturing of the cellular therapy product and therefore patients with a documented penicillin allergy are excluded from the trial)Patients with antibiotic allergies per se are not excluded; although the production of TIL for adoptive transfer includes antibiotics, extensive washing after harvest will minimize systemic exposure to antibiotics.

Sites / Locations

  • Moffitt Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment with Adoptive Cell Therapy

Arm Description

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).

Outcomes

Primary Outcome Measures

Safety of Adoptive Cell Therapy with TILs
Toxicity will be measured according to CTCAE v5. Investigators will determine if the serious toxicity rate exceeds 17%.

Secondary Outcome Measures

Overall Response Rate
Overall response is defined as the patient being alive 4 weeks after the adoptive TIL transfer, and the tumor size evaluated using the RECIST 1.1 criteria is consistent with a complete response (CR) or partial response (PR). The overall response (CR+PR) rate will be summarized using both a point estimate and its exact 95% confidence interval based on the binomial distribution.
Progression Free Survival
Progression-free survival (PFS), defined as the time from study entry to disease progression, relapse or death due to any cause, whichever is earlier, will be summarized with the Kaplan-Meier curve. Confidence intervals for the median and survival rates at different time points will be constructed if needed and appropriate. This secondary endpoint will be reported descriptively

Full Information

First Posted
March 2, 2023
Last Updated
October 17, 2023
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
United States Department of Defense
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1. Study Identification

Unique Protocol Identification Number
NCT05768347
Brief Title
Intravesical Adoptive Cell Therapy w/ TIL for BCG Exposed High Grade NMIBC
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 13, 2023 (Actual)
Primary Completion Date
February 2025 (Anticipated)
Study Completion Date
February 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
United States Department of Defense

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urothelial Carcinoma, Non-Invasive Bladder Urothelial Carcinoma
Keywords
Bladder cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment with Adoptive Cell Therapy
Arm Type
Experimental
Arm Description
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 Type
Biological
Intervention Name(s)
Adoptive Cell Therapy with Tumor-infiltrating Lymphocytes (TIL)
Intervention Description
Tissue samples are harvested, prepared and cryopreserved from post Bacillus Calmette-Guerin (BCG) bladder biopsies.
Primary Outcome Measure Information:
Title
Safety of Adoptive Cell Therapy with TILs
Description
Toxicity will be measured according to CTCAE v5. Investigators will determine if the serious toxicity rate exceeds 17%.
Time Frame
Up to 6 months
Secondary Outcome Measure Information:
Title
Overall Response Rate
Description
Overall response is defined as the patient being alive 4 weeks after the adoptive TIL transfer, and the tumor size evaluated using the RECIST 1.1 criteria is consistent with a complete response (CR) or partial response (PR). The overall response (CR+PR) rate will be summarized using both a point estimate and its exact 95% confidence interval based on the binomial distribution.
Time Frame
at 3 months
Title
Progression Free Survival
Description
Progression-free survival (PFS), defined as the time from study entry to disease progression, relapse or death due to any cause, whichever is earlier, will be summarized with the Kaplan-Meier curve. Confidence intervals for the median and survival rates at different time points will be constructed if needed and appropriate. This secondary endpoint will be reported descriptively
Time Frame
up to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Screening 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. Patients with active systemic infections requiring intravenous antibiotics within 1 week prior to enrollment. Any unresolved toxicity (>CTCAE v5 grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripheral neuropathy). History of pneumonitis or drug-related inflammatory lung disease. Active or prior documented autoimmune disease within the past 2 years. Note: Subjects with vitiligo, Grave's disease, limited site eczema, or limited site plaque psoriasis not requiring systemic treatment (within the past 2 years), or other autoimmune conditions which are not expected to recur, are allowed after approval from the medical monitor or PI. Patients with other prior malignancies must have had a ≥ 2-year disease-free interval, except for: in situ carcinoma of the cervix, in situ ductal carcinoma of the breast, in situ prostate cancer, in situ bladder cancer. These must have been deemed stable and not expected to relapse. In addition, early stage skin cancers, including basal, squamous cell cutaneous carcinoma, and melanoma, are permitted if previously treated with curative intent and not expected to relapse. Women who are pregnant or lactating. The effects of adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) infusion on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and until 4 months after completion of study drug administration. Those who do not agree must be excluded. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. WOCBP are defined as premenopausal women capable of becoming pregnant. Penicillin allergy (Penicillin is used in the manufacturing of the cellular therapy product and therefore patients with a documented penicillin allergy are excluded from the trial)Patients with antibiotic allergies per se are not excluded; although the production of TIL for adoptive transfer includes antibiotics, extensive washing after harvest will minimize systemic exposure to antibiotics.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael A Poch, MD
Organizational Affiliation
Moffitt Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kim Sprenger
Phone
813-745-0330
Email
kimberly.sprenger@moffitt.org
First Name & Middle Initial & Last Name & Degree
Michael A Poch, MD
First Name & Middle Initial & Last Name & Degree
Scott Gilbert, MD
First Name & Middle Initial & Last Name & Degree
Roger Li, MD
First Name & Middle Initial & Last Name & Degree
Brandon Manley, MD
First Name & Middle Initial & Last Name & Degree
Wade Sexton, MD
First Name & Middle Initial & Last Name & Degree
Philippe Spiess, MD
First Name & Middle Initial & Last Name & Degree
Alice Yu, MD
First Name & Middle Initial & Last Name & Degree
Logan Zemp, MD

12. IPD Sharing Statement

Links:
URL
https://www.moffitt.org/clinical-trials-research/clinical-trials/
Description
Moffitt Cancer Center Clinical Trials website

Learn more about this trial

Intravesical Adoptive Cell Therapy w/ TIL for BCG Exposed High Grade NMIBC

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