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Metastatic Bladder Urothelial CarcinomaPhase 2NCT03935347

Adoptive Cell Therapy With (LN-145) in Combination With Pembrolizumab in Treating Patients With Unresectable or Metastatic Transitional Cell Cancer Who Have Failed Cisplatin-Based Chemotherapy

A Phase 2 study testing Cyclophosphamide, Fludarabine and Fludarabine Phosphate in people with Metastatic Bladder Urothelial Carcinoma and Metastatic Renal Pelvis Urothelial Carcinoma, run by Roswell Park Cancer Institute at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial summary

This phase II trial studies how well autologous tumor infiltrating lymphocytes (LN-145) and pembrolizumab work in treating patients with transitional cell cancer that cannot be removed by surgery or has spread to other places in the body and have failed cisplatin-based chemotherapy. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cyclophosphamide, Fludarabine and Fludarabine Phosphate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
20 Jun 2019to 1 May 2023
Phase
Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The subject must understand the requirements of the study and voluntarily sign the informed consent form (ICF)
  • All subjects must have a histologically confirmed unresectable TCC (including renal pelvis, ureters, urinary bladder, and urethra)
  • Failed one and only one line of cisplatin-based chemotherapy per FDA guidelines.
  • Subjects must have an area of tumor amenable to excisional biopsy for the generation of TIL separate from, and in addition to , a target lesion to be used for response assessment.Have at least one resectable lesion to generate TILs
  • At least one measurable target lesion as defined by RECIST version 1.1
  • An Eastern Cooperative Oncology Group (ECOG) performance status of =< 1
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  • Estimated life expectancy of >= 6 months
  • Adequate bone marrow function
  • Adequate organ function
  • Subjects must be seronegative for the human immunodeficiency virus (HIV)
  • Recovered from all prior anticancer therapy-related AEs to grade 1 or less
  • Negative serum pregnancy test (female subjects of childbearing potential)
  • Subjects of childbearing potential must be willing to practice an approved method of birth control starting at the time of informed consent and for 12 months after the completion of the study treatment regimen
  • Must be able and willing to comply with the study visit schedule and protocol requirements including long-term follow-up

Who cannot join

  • Have had another primary malignancy within the previous 3 years (with the exception of carcinoma in situ of the breast, cervix, or localized prostate cancer and non-melanoma skin cancer that has been adequately treated)
  • Have received prior cell transfer therapy that included a nonmyeloablative or myeloablative chemotherapy regimen
  • Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody, or pathway-targeting agents
  • Chemotherapy or radiotherapy with projected completion within 4 weeks of initiating study treatment
  • Bisphosphonate therapy for symptomatic hypercalcemia
  • Have had treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2) within 6 weeks before initiation of study treatment
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  • Active or prior documented autoimmune or inflammatory disorders
  • Subjects who have any form of human immondeficiency virus (HIV)infection
  • Have severe infections within 4 weeks before initiation of study treatment
  • Have received a live or attenuated vaccine within 28 days of the non-myeloablative lymphodepletion (NMA-LD regimen)
  • Subjects with a history of hypersensitivity reaction(s) to any component of the LN-145 therapy and/or the other study drugs
  • Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) >= 450 msec for males (and >= 470 msec for females) calculated from 3 electrocardiograms (ECGs) (within a 30-minute timeframe) or history of familiar long-QT syndrome
  • Subjects who have a left ventricular ejection fraction (LVEF) < 45% or who are New York Heart Association functional classification class II or higher
  • Serious illnesses or medical conditions, which would pose increased risk for study participation and/or compliance with the protocol
  • Known clinically significant liver disease
  • Have obstructive or restrictive pulmonary disease and have a documented FEV1 (forced expiratory volume in 1 second) of =< 60%
  • Subjects with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases
  • Subjects who are pregnant or breastfeeding
  • Active infection including tuberculosis (TB), hepatitis B, hepatitis C, or human immunodeficiency virus
  • Treatment with any other investigational agent within 4 weeks before initiation of study treatment

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263-0001

Other trials in United States

About this study

Official title: Phase 2 Study of Autologous Tumor Infiltrating Lymphocytes (LN-145) With Pembrolizumab, in Subjects Who Have Failed Cisplatin-Based Chemotherapy With Locally Advanced (Unresectable) or Metastatic Transitional Cell Cancer (TCC) of the Urothelium

This phase II trial studies how well autologous tumor infiltrating lymphocytes (LN-145) and pembrolizumab work in treating patients with transitional cell cancer that cannot be removed by surgery or has spread to other places in the body and have failed cisplatin-based chemotherapy. LN-145 is made up of specialized immune cells called lymphocytes or T cells that are taken from a patient's tumor, grown in a manufacturing facility and infused back into the preconditioned patient to attack the tumor. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving LN-145 may help control transitional cell bladder cancer when given together with pembrolizumab

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the efficacy of autologous tumor infiltrating lymphocytes LN-145 (LN-145) in combination with pembrolizumab in subjects with advanced transitional cell bladder cancer (TCC) using the objective response rate (ORR) and the duration of response (DoR), using the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST version [v] 1.1).

SECONDARY OBJECTIVES:

  1. To evaluate the efficacy of LN-145 in combination with pembrolizumab in subjects with TCC based on the progression-free survival (PFS) and overall survival (OS).

II. To evaluate the safety of LN-145 in combination with pembrolizumab in subjects with TCC based on the adverse event (AE) profile per Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v5.0).

Being tested
Cyclophosphamide, Fludarabine, Fludarabine Phosphate, Pembrolizumab, Autologous Tumor Infiltrating Lymphocytes LN-145

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Also called 1-bis(2-chloroethyl)-amino-1-oxo-2-aza-5-oxaphosphoridin monohydrate, 2-[bi(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate, Cyclostine, Revimmune

    Given IV

  • FludarabineDrug

    Also called 118218, 2-Fluoro-9-beta-arabinofuranosyladenine, 2-Fluorovidarabine, 21679-14-1, 9-Beta-D-arabinofuranosyl-2-fluoro-9H-purin-6-amine

    Given IV

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, 312887, 328002, 75607-67-9

    Given IV

  • PembrolizumabBiological

    Also called 1374853-91-4, Immunoglobulin G4, Anti-(Human Programmed Cell Death 1)

    Given IV

  • Autologous Tumor Infiltrating Lymphocytes LN-145Biological

    Also called Autologous TILs LN-145, LN-145, LN145

    Given IV

  • AldesleukinBiological

    Also called 110942-02-4, 125-L-Serine-2-133-interleukin 2, Recombinant Human Interleukin-2

    Given IV

Study groups in NCT03935347
Study groupRoleWhat they receive
Treatment (cyclophosphamide, fludarabine, pembrolizumab)ExperimentalPatients receive cyclophosphamide IV over 2 hours on days -8 and -7, fludarabine IV over 30 minutes on days -6 to -2, and pembrolizumab IV over 30 minutes on day -1. At least 24 hours later, patients receive autologous tumor infiltrating lymphocytes LN-145 IV on day 0, and receive aldesleukin IV over 30 minutes for up to 6 doses on days 1-4. Patients then continue receiving pembrolizumab IV over 30 minutes beginning on day 21. Cycles of pembrolizumab repeat every 21 days for 12 months in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Fludarabine Phosphate; Biological: Pembrolizumab; Biological: Autologous Tumor Infiltrating Lymphocytes LN-145; Biological: Aldesleukin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective response rate

    The proportion of subjects who achieve either a confirmed partial response (PR) or complete response (CR) as best response as assessed per Response Evaluation Criteria in Solid Tumors 1.1. Will be evaluated per each disease assessment and calculated with the corresponding 95% two-sided confidence interval

    Measured: Up to 3 years

Secondary outcomes (5)

  1. Incidence of adverse events (AEs)

    Will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 5 by grade of severity and relationship to the study treatment.

    Measured: From the first dose of cyclophosphamide up to 30 days from the last dose of IL-

  2. Duration of response

    Will be assessed by Kaplan-Meier methods

    Measured: Up to 3 years

  3. Disease Control Rate

    Derived as the sum of the number of subjects who achieved confirmed PR/CR or sustained stable disease (at least 6 weeks) divided by the number of subjects in the all-treated population x 100%. Will be assessed by Kaplan-Meier methods

    Measured: Up to 3 years

  4. Progression-free survival

    Will be assessed by Kaplan-Meier methods

    Measured: Up to 3 years

  5. Overall Survival

    From time of lymphodepletion to death due to any cause

    Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 May 2019
  2. Study start20 Jun 2019
  3. Primary completion1 May 2022 (estimated)
  4. Study completion1 May 2023 (estimated)

Why it stopped: no accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03935347
Sponsor's protocol ID
I 77218
Other IDs
P30CA16056OD, P30CA016056
Status last verified
Dec 2019
First submitted
30 Apr 2019
Last updated
2 Jan 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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