NCT04383067

Brief Summary

An autologous, Adoptive Cell Therapy Following a Reduced Intensity, Non-myeloablative, Lymphodepleting Induction Regimen in Metastatic Urothelial Carcinoma Patients.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
20

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started May 2020

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 3, 2020

Completed
8 days until next milestone

First Posted

Study publicly available on registry

May 11, 2020

Completed
1 day until next milestone

Study Start

First participant enrolled

May 12, 2020

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2022

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2023

Completed
Last Updated

February 11, 2021

Status Verified

May 1, 2020

Enrollment Period

2.1 years

First QC Date

May 3, 2020

Last Update Submit

February 8, 2021

Conditions

Metastatic Urothelial Carcinoma

Keywords

Urothelial cancerTumor infiltrating lymphocytesCellular therapy

Outcome Measures

Primary Outcomes (2)

  • Efficacy endpoint Objective Tumor response according to RECICT 1.1

    The primary efficacy endpoint is defined as at least a 20% clinical benefit expressed as the sum of CR+PR+SD (each of these parameters defined as persisting for at least for 12 weeks).

    3 Years

  • Safety endpoint Assess Adverse Events using CTCAE V4.03 during treatment and FU

    The primary safety endpoint of the study is to evaluate the overall toxicity profile of the ACT procedure, with an emphasis on the side effects of the reduced intensity, non-myeloablative, lymphodepleting induction regimen.

    3 Years

Secondary Outcomes (3)

  • Overall Survival

    3 Years

  • Progression-Free Survival

    3 Years

  • Quality of Life (QoL) Assessment

    3 Years

Other Outcomes (2)

  • Tissue markers assessment

    3 Years

  • Blood Bio-markers assessment

    3 Years

Study Arms (1)

Tumor Infiltrating Lymphocytes (TIL)

EXPERIMENTAL
Procedure: Tumor Infiltrating Lymphocytes (TIL)Drug: Proleukin

Interventions

Tumor Infiltrating Lymphocytes (TIL)PROCEDURE

Patient with metastatic urothelial carcinoma will undergo a autologous lymphocyte transplantation. Patient will undergo surgery to remove either the primary tumor or a tumor metastasis. The cells collected in this surgey will be cultured and reintroduced to the patient. Following the cell infusion, patient will receive a high-dose bolus of IL-2.

Tumor Infiltrating Lymphocytes (TIL)
ProleukinDRUG

high-dose (720,000 IU/kg) IL-2 will be administered every 8 hours, to tolerance. A maximum of 10 doses will be administered

Tumor Infiltrating Lymphocytes (TIL)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically confirmed Urothelial Carcinoma
  • Progressed on first line platinum-based chemotherapy and on second line immunotherapy or targeted therapy (FGFR inhibitor)
  • Measurable metastatic Urothelial Carcinoma with at least one lesion that is resectable for TIL generation.
  • Patients with one or more brain metastases less than 1 cm each, and any patients with 1 or 2 brain metastases greater than 1 cm must have been treated and stable for 4 weeks.
  • Greater than or equal to 18 years of age.
  • Willing to practice birth control from the start of chemotherapy until 120 days after release from the hospital.
  • Life expectancy of greater than three months
  • Willing to sign a durable power of attorney
  • Able to understand and sign the Informed Consent Document
  • Clinical performance status of ECOG 0 or 1
  • Hematology:
  • Absolute neutrophil count greater than 1000/mm3 without support of filgrastim
  • Normal WBC ( \> 3000/mm3).
  • Hemoglobin greater than 8.0 g/dL
  • Platelet count greater than 100,000/mm3
  • +9 more criteria

You may not qualify if:

  • Upper tract Urothelial Carcinoma
  • History of nephrectomy
  • Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the non-myeloablative, lymphodepleting induction regimen on the fetus or infant.
  • Systemic steroid therapy required (patients that require replacement therapy for adrenal insufficiency may be enrolled if steroid treatment dose do not exceed 10 mg of prednisone or equivalent).
  • Active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
  • Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).
  • Opportunistic infections (the experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities.)
  • History of severe immediate hypersensitivity reaction to any of the agents used in this study, including history of an anaphylactic reaction to penicillin or gentamicin
  • History of coronary revascularization or ischemic heart disease.
  • Any patient known to have an LVEF less than or equal to 50%.
  • Documented LVEF of less than or equal to 50% tested in patients with clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second- or third-degree heart block
  • Documented FEV1 and DLCO (relative to predicted) less than or equal to 60%

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Sheba Medical Center

Ramat Gan, 5262100, Israel

RECRUITING

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

aldesleukin

Condition Hierarchy (Ancestors)

CarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasms

Central Study Contacts

Ronnie Shapira, MD.

CONTACT

+972-3-5308414Ronnie.Shapira@sheba.health.gov.il

Meital Bar

CONTACT

+972-3-5305201meital.bar@sheba.health.gov.il

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER GOV
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director , The Ella Lemelbaum Institute of Immuno-Oncology, Principal Investigator, Associate Professor of Immunology

Study Record Dates

First Submitted

May 3, 2020

First Posted

May 11, 2020

Study Start

May 12, 2020

Primary Completion

June 1, 2022

Study Completion

June 1, 2023

Last Updated

February 11, 2021

Record last verified: 2020-05

Locations

IL(1)