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Clinical Trial Record

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Adoptive Transfer of Tumor Infiltrating Lymphocytes for Advanced Solid Cancers

2019-12-03

2037-06-30

2038-06-30

240

Study Overview

Adoptive Transfer of Tumor Infiltrating Lymphocytes for Advanced Solid Cancers

This is a Phase 2 study to evaluate the efficacy of a non-myeloablative lymphodepleting preparative regimen followed by infusion of autologous TIL and high-dose aldesleukin in patients with locally advanced, recurrent, or metastatic cancer associated with one of the following cancer types: 1.) gastric/esophagogastric, 2.) colorectal, 3.) pancreatic, 4.) sarcoma, 5.) mesothelioma, 6.) neuroendocrine, 7.) squamous cell cancer, 8.) Merkle cell, 9.) mismatch repair deficient and/or microsatellite unstable cancers, and 10.) patients who have exhausted conventional systemic therapy options by using the objective response rate (ORR).

This Phase 2 study will be conducted in conjunction with companion protocol (Cell Harvest and Preparation to Support Adoptive Cell Therapy Clinical Protocols and Pre-Clinical Studies) as described below: Cell Preparation: Patients with evaluable locally advanced, recurrent, or metastatic gastric/esophagogastric, colorectal, pancreatic, sarcoma, mesothelioma, neuroendocrine, cutaneous/anal squamous cell, Merkel cell, cancers refractory to systemic therapy, and those with deficient mismatch repair and/or microsatellite instability cancers who have lesions that can be resected or biopsied with minimum morbidity will undergo resection or biopsy of tumor. TIL will be obtained while enrolled on the companion protocol HCC 17-220 (Cell Harvest and Preparation to Support Adoptive Cell Therapy Clinical Protocols and Pre-Clinical Studies). Separate tumor procurements may be performed under HCC 17-220 protocol to obtain TIL if initial tumor procurements could not successfully generate TIL. The TIL will be grown and expanded for this trial according to standard operating procedures submitted in the IND. The TIL will be assessed for potency by interferon-gamma release. Treatment Phase: Once cells exceed the potency requirement and are projected to exceed the minimum number specified in the COA, the patient will be registered on this study and receive the lymphocyte depleting preparative regimen consisting of fludarabine and cyclophosphamide, followed by infusion of up to 2x10^11 lymphocytes (minimum of 1x10^9 cells) and administration of high-dose intravenous aldesleukin. It is anticipated that TIL that meet the COA will not be achievable in approximately 20% of patients who undergo resection. These patients may undergo a second resection to grow TIL, if another suitable lesion exists. Approximately 6 weeks (+/- 2 weeks) after TIL administration, patients will undergo a complete tumor evaluation and evaluation of toxicity and immunologic parameters. Patients will receive one course of treatment. The start date of the course will be the start date of the chemotherapy; the end date will be the day of the first post-treatment evaluation. Patients may undergo a second treatment. Patients will receive no other experimental agents while on this protocol.

  • Gastric Cancer
  • Colorectal Cancer
  • Pancreatic Cancer
  • Sarcoma
  • Mesothelioma
  • Neuroendocrine Tumors
  • Squamous Cell Cancer
  • Merkel Cell Carcinoma
  • Mismatch Repair Deficiency
  • Microsatellite Instability
  • BIOLOGICAL: Tumor Infiltrating Lymphocytes (TIL)
  • DRUG: Fludarabine + Cyclophosphamide combination
  • 19-004

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 Registration Dates Results Reporting Dates Study Record Updates

2019-04-26  

N/A  

2025-07-07  

2019-05-01  

N/A  

2025-07-10  

2019-05-02  

N/A  

2025-07  

Study Plan

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

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/ArmIntervention/Treatment
EXPERIMENTAL: Tumor Infiltrating Lymphocytes (TIL)

Patients with locally advanced, recurrent, or metastatic gastric/esophagogastric, colorectal, pancreatic, sarcoma, mesothelioma, neuroendocrine, cutaneous/anal squamous cell, Merkel cell, cancers refractory to systemic therapy, and those with deficient mi

BIOLOGICAL: Tumor Infiltrating Lymphocytes (TIL)

  • TIL are to be infused intravenously through a central vein catheter over 20-30 minutes followed by Aldesleukin, administered at a dose of 600,000 IU/kg (based on total body weight) as an intravenous bolus over a 15-minute period approximately every 8 hour

DRUG: Fludarabine + Cyclophosphamide combination

  • Preparative lymphocyte depleting (immunosuppressive) combination regimen consisting of fludarabine and cyclophosphamide administered prior to TIL infusion.
Primary Outcome MeasuresMeasure DescriptionTime Frame
Objective Response Rate (ORR)Number of patients with Complete Response (CR) + Number of patients with Partial Response (PR) / total number of patients (# with CR + # with PR + # with SD + # with PD), per RECIST v1.1: CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: ≥ 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study. Progressive Disease (PD): ≥ 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance ≥1 new lesion(s) is considered progression.24 months
Secondary Outcome MeasuresMeasure DescriptionTime Frame
Complete Response Rate (CRR)Proportion of patients with complete response per Response Evaluation Criteria in Solid Tumors (RECIST v1.1): Number of patients with Complete Response (CR) / total number of patients (# with CR + # with PR + # with SD + # with PD). CR: disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to <10 mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study. Progressive Disease (PD): ≥ 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance ≥1 new lesion(s) is considered progression.24 months
Duration of response (DOR)Time between the initial response to treatment per Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) and subsequent disease progression among patients achieving Complete Response (CR) or Partial Response (PR). Per RECIST v1.1, Complete Response (CR): disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.24 months
Disease control rate (DCR)Number of patients with Complete Response (CR) + Number of patients with Partial Response (PR) + Number of patients with Stable Disease (SD) / total number of patients (# with CR + # with PR + # with SD + # with PD), per RECIST v1.1. (CR):disappearance of all target lesions.Any pathological lymph nodes (target or non-target) with reduction in short axis to <10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD):Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.24 months
Progression-free survival (PFS)The length of time after TIL infusion treatment that a patient lives with disease that does not progress per RECIST v1.1. Per RECIST, Progressive Disease (PD): ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.24 months
Overall survival (OS)The length of time from the start of treatment that patients are still alive.24 months

Contacts and Locations

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

Study Contact

Name: Josh Tobin

Phone Number: 412-864-7754

Email: tobinja@upmc.edu

Study Contact Backup

Name: Allyson Welsch

Phone Number: 412-623-6763

Email: welscha2@upmc.edu

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.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

    Inclusion Criteria:
    Measurable locally advanced, recurrent, or metastatic cancer associated with one of the following cancer types: 1.) gastric/esophagogastric, 2.) colorectal, 3.) pancreatic, 4.) sarcoma, 5.) mesothelioma, 6.) neuroendocrine, 7.) squamous cell cancer, 8.) Merkle cell, 9.) mismatch repair deficient and/or microsatellite unstable cancers, and 10.) patients who have exhausted conventional systemic therapy options
    Patients with locally advanced disease should be unresectable by conventional surgical approaches.
    Patients with distant metastatic spread must have previously received approved first-line systemic therapies if they are eligible to receive these treatments.
    Patients must be co-enrolled on the companion protocol HCC 17-220 (Cell Harvest and Preparation to Support Adoptive Cell Therapy Clinical Protocols and Pre-Clinical Studies) and have available TIL cultures for therapy.
    Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible.
    Greater than or equal to 18 years of age and less than or equal to age 75
    Able to understand and sign the Informed Consent Document
    Clinical performance status of ECOG 0 or 1
    Life expectancy of greater than three months
    Patients of both genders who are of child-bearing potential must be willing to practice birth control from the time of enrollment on this study and for up to four months after receiving the treatment.
    Serology:

  • Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
  • Seronegative for hepatitis B antigen
  • Seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.

    • Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus.
    Hematology

  • Absolute neutrophil count greater than 1000/mm3 without the support of filgrastim
  • WBC ≥ 3000/mm3
  • Platelet count ≥ 100,000/mm3
  • Hemoglobin > 8.0 g/dl

    • Chemistry

  • Serum ALT/AST ≤ to 3.5 times the upper limit of normal Serum creatinine ≤ to 1.6 mg/dl
  • Total bilirubin ≤ to 2.0 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.

    • More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' toxicities must have recovered to a clinically manageable level (except for toxicities such as alopecia or vitiligo). (Note: Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less)
    Exclusion Criteria:
    Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
    Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
    Concurrent 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).
    Active systemic infections (e.g.: requiring anti-infective treatment),
    Clinically significant coagulation disorder
    Active major medical illnesses deemed clinically significant by the treating physician
    History of clinically significant major organ autoimmune disease
    Patients with a history of hypothyroidism are eligible
    Concurrent systemic steroid therapy.
    History of severe immediate hypersensitivity reaction to any of the agents used in this study.
    History of active coronary or ischemic symptoms.
    Documented LVEF of less than or equal to 45%; note: testing is required in patients with:

  • Age > 65 years' old
  • Clinically significant atrial and or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second- or third-degree heart block or have a history of ischemic heart disease, chest pain.

    • Documented FEV1 less than or equal to 60% predicted tested in patients with:

  • A prolonged history of cigarette smoking (20 pk/year of smoking within the past 2 years).
  • Symptoms of respiratory dysfunction

    • Patients who are receiving any other investigational agents.

Collaborators and Investigators

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

    • PRINCIPAL_INVESTIGATOR: Udai S Kammula, MD, UPMC Hillman Cancer Center

    Publications

    The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

    General Publications

    No publications available

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