A Study Using Tumor-Reactive Autologous Tumor Infiltrating Lymphocytes (TIL) in Metastatic Melanomas (TIL)

August 27, 2021 updated by: Saint John's Cancer Institute

A Phase II Study Using Tumor-Reactive Autologous Tumor Infiltrating Lymphocytes (TIL) Plus IL-2 Followed by Lymphocyte Depleting Chemotherapy Regimen in Metastatic Melanomas

The purpose of this protocol is to determine whether autologous TIL infused in conjunction with systemic high-dose IL-2 after non-myeloablative chemotherapy with cyclophosphamide and fludarabine can cause consistent and durable objective responses in patients who have metastatic melanoma at the John Wayne Cancer Institute (JWCI).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Santa Monica, California, United States, 90404
        • John Wayne Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria -

  • Patients must have metastatic melanoma with a resectable metastatic lesion of sufficient size and be willing to undergo such a resection for experimental purposes.
  • Patients must be > 18 years of age.
  • Patients must have measurable disease measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria (in addition to the resected lesion).
  • Patients of child bearing potential must agree to use an effective form of birth control during study and up to four months after receiving treatment.
  • Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0-1.
  • Absolute neutrophil count greater than 1000/mm3 without support of filgrastim.
  • Platelet count greater than 100,000/mm3.
  • Serum Alanine transaminase/Aspartate transaminase (ALT/AST) less than three times the upper limit of normal.
  • Serum creatinine less than or equal to 1.6 mg/dl.
  • Total bilirubin less than or equal to 2 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3 mg/dl.
  • Patients must be able to understand and sign the Informed Consent document.

Exclusion Criteria - Tumor/TIL Harvest Exclusion Criteria

  • All systemic, cytotoxic therapy (including targeted therapies) must be stopped at least 5 weeks prior to cell infusion (see 2.1.3).
  • Women who are pregnant or breastfeeding.
  • Life expectancy of less than three months.
  • Patients who have received prior treatment with anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) antibody will be excluded unless a post anti-CTLA-4 antibody treatment colonoscopy was normal with normal colonic biopsies.
  • Patients who require immediate active treatment for symptomatic Central Nervous System (CNS) lesions will not be eligible until after treatment of their symptomatic lesions.

Cell Infusion Exclusion Criteria

  • Less than 5 weeks has elapsed since any prior systemic therapy at the time the patient receives the preparative regimen. All patients' toxicities must have recovered to a grade 1 or less or as specified in the eligibility criteria in Section 2.1.1. Patients may have undergone minor surgical procedures or focal palliative radiotherapy (to non-target lesions) within the past 5 weeks, as long as all toxicities have recovered to grade 1 or less or as specified in the eligibility criteria in Section 2.1.1.
  • Women of child-bearing potential who are pregnant or breastfeeding.
  • Life expectancy of less than three months.
  • Systemic steroid therapy more than the equivalent of 10mg/day of prednisone.
  • Hemoglobin less than 8g/dl unable to be corrected with transfusion.
  • Any 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 or secondary immunodeficiency. Must have recovered immune competence after chemotherapy or radiation therapy as evidenced by normal Absolute Neutrophil Count (ANC) > 1000/mm3 and absence of 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.)
  • Seropositive for HIV antibody.
  • Patients with active hepatitis B or active hepatitis C.
  • The following patients will be excluded because of inability to receive high dose proleukin:
  • Patients will be excluded if they have a history of major EKG abnormalities, symptoms of cardiac ischemia or arrhythmias and have a Left Ventricular Ejection Fraction (LVEF) < 45% on a cardiac stress test (stress thallium, stress Multi Gated Acquisition Scan (MUGA), dobutamine, echocardiogram or other stress test)
  • Patients who have a prolonged history of cigarette smoking or symptoms of respiratory dysfunction will be excluded if they have an abnormal pulmonary function test as evidenced by a Forced Expiratory Volume at one second Forced Expiratory Volume at one second (FEV1)< 60% predicted.
  • Patients who have received prior treatment with anti-CTLA-4 antibody will be excluded unless a subsequent colonoscopy was normal with normal colonic biopsies (to rule out colitis).
  • Patients who require immediate treatment for symptomatic CNS lesions will not be eligible until after treatment of their symptomatic lesions and resolution of symptoms.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Tumor Infiltrating Lymphocytes (TIL)
Patients will have a melanoma metastasis resected and cultured in IL-2 in vitro either as part of this treatment protocol or the JWCI procurement protocol. TIL from these cultures will be assessed for tumor-reactivity and those with such activity will be further expanded and adoptively transferred. Patients will receive a non-myeloablative lymphocyte-depleting preparative regimen consisting of cyclophosphamide (60 mg/kg/day X 2 days IV) and fludarabine (25 mg/m2/day IV X 5 days). Following this regimen, patients will receive an intravenous adoptive transfer of at least 109 tumor-reactive lymphocytes (TIL) followed by high-dose intravenous IL-2 (600-720,000 IU/kg/dose every 8 hours for up to 12 doses).
Biological: Tumor Infiltrating Lymphocytes (TIL)
Patients will receive an IV adoptive transfer of at least 10^9 tumor-reactive lymphocytes. An IV catheter in the patient's arm or upper chest will be used for cell infusion. The TIL will be administered over 20-30 minutes at room temperature using a standard infusion protocol or by hanging the infusion bag from a stand and allowing gravity to pull the cells down.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Clinical Response
Time Frame: 12 weeks, or until development of new metastases or recurrence
At the end of 12 week follow up, the proportion of patients that showed clinical response (CR) determined by the disappearance of all target lesions, or partial response (PR) will be calculated. The patient is determined to have partial response as if 30% reduction in the sum of the longest diameter (SLD) of target lesions are shown from the baseline sum LD.
12 weeks, or until development of new metastases or recurrence

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Quality of Life
Time Frame: 12 weeks, or until development of new metastases or recurrence
Quality of Life will be assessed and scored per European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) EORTC-QLQ-C30 version 3.0 requirements. The EORTC QLQ-C30 contains subscales for global health status, and physical, emotional, role, cognitive and social function with higher scores indicating better functioning (19). The change in QOL measured throughout the study period will be examined through mixed effect model adjusting for the baseline. Akaike information criteria (AIC) will be used to determine appropriate covariance structure.
12 weeks, or until development of new metastases or recurrence

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Saint John's Cancer Institute

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Mark Faries, MD., FACS, Saint John's Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 16, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 25, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 2, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 3, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 22, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 27, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TIL-TREATMENT-0614

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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