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innovaTIL-01, Study of Lifileucel (LN-144), Autologous Tumor Infiltrating Lymphocytes, in the Treatment of Patients With Metastatic Melanoma (LN-144)

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ClinicalTrials.gov Identifier: NCT02360579
Recruitment Status : Recruiting
First Posted : February 10, 2015
Last Update Posted : April 3, 2019
Sponsor:
Information provided by (Responsible Party):
Iovance Biotherapeutics, Inc.

Brief Summary:
Prospective, interventional multicenter study evaluating adoptive cell therapy (ACT) via infusion of LN-144 (autologous TIL) followed by interleukin 2 (IL-2) after a nonmyeloablative lymphodepletion (NMA LD) preconditioning regimen.

Condition or disease Intervention/treatment Phase
Metastatic Melanoma Biological: Lifileucel Phase 2

Detailed Description:
Lifileucel is an autologous adoptive cell transfer therapy that utilizes a TIL manufacturing process, as originally developed by the NCI, for the treatment of patients with metastatic melanoma. The adoptive cell transfer therapy used in this study involves patients receiving a lymphocyte depleting preconditioning regimen, prior to infusion of autologous TIL, followed by the administration of a regimen of IL-2.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 164 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter Study to Assess the Efficacy and Safety of Autologous Tumor Infiltrating Lymphocytes (LN-144) for Treatment of Patients With Metastatic Melanoma
Study Start Date : September 2015
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Cohort 1
Lifileucel (LN-144) without cryopreservation (Gen 1 infusion product) (Closed)
Biological: Lifileucel
A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After lymphodepletion, patients are infused with Lifileucel followed by IL-2.
Other Name: LN - 144

Experimental: Cohort 2
Cryopreserved lifileucel (LN-144) (Gen 2 infusion product) (Closed)
Biological: Lifileucel
A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After lymphodepletion, patients are infused with Lifileucel followed by IL-2.
Other Name: LN - 144

Experimental: Cohort 3
Retreatment cohort: patients from Cohort 1, Cohort 2 or Cohort 4 may rescreen for a second TIL regimen therapy if they meet all Inclusion and Exclusion Criteria (except exclusion criterion b).
Biological: Lifileucel
A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After lymphodepletion, patients are infused with Lifileucel followed by IL-2.
Other Name: LN - 144

Experimental: Cohort 4
Cryopreserved lifileucel (LN-144) (Gen 2 infusion product)
Biological: Lifileucel
A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After lymphodepletion, patients are infused with Lifileucel followed by IL-2.
Other Name: LN - 144




Primary Outcome Measures :
  1. Disease Assessment for Objective Response Rate [ Time Frame: Every 6 weeks for 6 months, then every 3 months for a maximum of 54 months ]
    Evaluate the efficacy of LN-144 in patients with unresectable or metastatic melanoma using the objective response rate (ORR), as assessed by the Blinded Independent Review Committee (BIRC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1


Secondary Outcome Measures :
  1. Disease Assessment for Duration of Response [ Time Frame: Every 6 weeks for 6 months, then every 3 months for a maximum of 54 months ]
    Evaluate the efficacy endpoints of duration of response (DOR) by the BIRC and by the investigator per RECIST v1.1

  2. Disease Assessment for Disease Control Rate [ Time Frame: Every 6 weeks for 6 months, then every 3 months for a maximum of 54 months ]
    Evaluate the efficacy endpoints of disease control rate (DCR) as assessed by the BIRC and by the investigator per RECIST v1.1

  3. Disease Assessment for Progression-Free Survival [ Time Frame: Every 6 weeks for 6 months, then every 3 months for a maximum of 54 months ]
    Evaluate the efficacy endpoints of progression-free survival (PFS) as assessed by the BIRC and by the investigator per RECIST v1.1

  4. Overall Survival [ Time Frame: Until death or up to 60 months ]
    Evaluate overall survival (OS) and objective response rate (ORR) by the investigator

  5. Adverse Events [ Time Frame: Maximum 60 months ]
    Incidence rate of treatment-emergent adverse events (AEs) and serious AEs by severity and relationship to Lifileucel (LN-144).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Patients must meet all of the following inclusion criteria to be eligible for participation in the study:

Criteria for Inclusion:

  1. Patients with unresectable or metastatic melanoma (Stage IIIc or Stage IV)
  2. Patients must have progressed following ≥ one prior systemic therapy including a programmed cell death protein-1 (PD-1) blocking antibody; and if proto-oncogene B-Raf (BRAF) V600 mutation-positive, a BRAF inhibitor or BRAF inhibitor in combination with mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor
  3. At least one measurable target lesion, as defined by RECIST v1.1

    • Lesions in previously irradiated areas (or other local therapy) should not be selected as target lesions, unless treatment was ≥ 3 months prior to Screening, and there has been demonstrated disease progression in that particular lesion
  4. At least one resectable lesion (or aggregate of lesions resected) of a minimum 1.5 cm in diameter post-resection to generate TIL; surgical removal with minimal morbidity (defined as any procedure for which expected hospitalization is ≤ 3 days)
  5. Patients must be ≥ 18 years of age at the time of consent. Enrollment of patients > 70 years of age may be allowed after consultation with the Medical Monitor
  6. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and an estimated life expectancy of ≥ 3 months
  7. In the opinion of the Investigator, patients must be able to complete all study-required procedures
  8. Patients must have the following hematologic parameters:

    • Absolute neutrophil count (ANC) ≥ 1000/mm3
    • Hemoglobin (Hb) ≥ 9.0 g/dL
    • Platelet ≥ 100,000/mm3
  9. Patients must have adequate organ function:

    • Serum alanine transaminase (ALT)/serum glutamic-pyruvic transaminase (SGPT) and aspartate transaminase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) ≤ 3 times the upper limit of normal (ULN); patients with liver metastasis ≤ 5 times ULN
    • Estimated creatinine clearance (eCrCl) ≥ 40 mL/min using the Cockcroft-Gault formula
    • Total bilirubin ≤ 2 mg/dL
    • Patients with Gilbert's syndrome must have a total bilirubin ≤ 3 mg/dL
  10. Patients must have recovered from all prior therapy-related adverse events (AEs) to ≤ Grade 1 (per Common Terminology Criteria for Adverse Events [CTCAE] v4.03), except for alopecia or vitiligo, prior to Enrollment (tumor resection)

    • Patients with documented ≥ Grade 2 diarrhea or colitis as a result of previous treatment with immune checkpoint inhibitor(s) must have been asymptomatic for at least 6 months and/or had a normal colonoscopy post-immune checkpoint inhibitor treatment, by visual assessment, prior to tumor resection
  11. Patients must have a washout period ≥ 28 days from prior anticancer therapy(ies) to the start of the planned NMA-LD preconditioning regimen:

    • Targeted therapy: MEK/BRAF or other targeted agent
    • Chemotherapy
    • Immunotherapy: anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)/anti-PD-1, other monoclonal antibody (mAb), or vaccine
    • Palliative radiation therapy is permitted so long as it does not involve lesions being selected for TIL, or as target or non-target lesions. Washout is not required if all related toxicities have resolved to ≤ Grade 1 as per CTCAE v4.03
  12. Patients of childbearing potential or their partners of childbearing potential must be willing to take the appropriate precaution to avoid pregnancy or fathering a child for the duration of the study and practice an approved, highly effective method of birth control during treatment and for 12 months after receiving the last protocol-related therapy

    • Approved methods of birth control are as follows:
    • Combined (estrogen and progesterone containing) hormonal birth control associated with inhibition of ovulation: oral, intravaginal, transdermal
    • Progesterone-only hormonal birth control associated with inhibition of ovulation: oral, injectable, implantable
    • Intrauterine device (IUD)
    • Intrauterine hormone-releasing system (IUS)
    • Bilateral tubal occlusion
    • Vasectomized partner
    • True sexual abstinence when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar ovulation, symptothermal, post-ovulation methods) is not acceptable
  13. Patients (or legally authorized representative) must have the ability to understand the requirements of the study, have provided written informed consent as evidenced by signature on an ICF approved by an Institutional Review Board/Independent Ethics Committee (IRB/IEC), and agree to abide by the study restrictions and return to the site for the required assessments, including the OS Follow-up Period
  14. Patients have provided written authorization for use and disclosure of protected health information

Criteria for Exclusion:

Patients who meet any of the following criteria are not eligible for participation in this study:

  1. Patients who have been shown to be BRAF mutation positive (V600), but have not received prior systemic therapy with a BRAF inhibitor alone or a BRAF inhibitor in combination with a MEK inhibitor
  2. Patients who have received an organ allograft or prior cell transfer therapy
  3. Patients with melanoma of uveal/ocular origin
  4. Patients who have a history of hypersensitivity to any component or excipient of LN-144 or other study drugs:

    • NMA-LD preconditioning regimen (cyclophosphamide, mesna, and fludarabine)
    • Antibiotics (ABX) of the aminoglycoside group (ie, streptomycin, gentamicin); except those who are skin-test negative for gentamicin hypersensitivity
    • Any component of the LN-144 infusion product formulation including dimethyl sulfoxide (DMSO), human serum albumin (HSA), IL-2, and dextran-40
  5. Patients with symptomatic and/or untreated brain metastases (of any size and any number)

    • Patients with definitively treated brain metastases may be considered for Enrollment, and must be stable for ≥ 14 days prior to beginning the NMA LD preconditioning regimen
  6. Patients who are on chronic systemic steroid therapy for any reason
  7. Patients who have active medical illness(es) that would pose increased risk for study participation, including: active systemic infections requiring systemic ABX, coagulation disorders, or other active major medical illnesses of the cardiovascular, respiratory, or immune system
  8. Patients who have any form of primary immunodeficiency (such as severe combined immunodeficiency disease [SCID] and acquired immunodeficiency syndrome [AIDS])
  9. Patients who have a left ventricular ejection fraction (LVEF) < 45% or New York Heart Association (NYHA) functional classification > Class 1

    • Patients ≥ 60 years of age and who have a history of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias must have a cardiac stress test. Patients with any irreversible wall movement abnormalities are excluded
  10. Patients who have a documented forced expiratory volume in 1 second (FEV1) of ≤ 60%
  11. Patients who have had another primary malignancy within the previous 3 years (with the exception of carcinoma in situ of the breast, cervix, or bladder; localized prostate cancer; and non-melanoma skin cancer that has been adequately treated)
  12. Patients who have received a live or attenuated vaccine within 28 days of beginning the NMA-LD preconditioning regimen
  13. Patients who are pregnant or breastfeeding
  14. Patients whose cancer requires immediate attention or who would otherwise suffer a disadvantage by participating in this trial
  15. Patients protected by the following constraints:

    • Hospitalized persons without consent or persons deprived of liberty because of a judiciary or administrative decision
    • Adult persons with a legal protection measure or persons who cannot express their consent
    • Patients in emergency situations who cannot consent to participate in the trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02360579


Contacts
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Contact: Iovance Biotherapeutics Clinical Inquiries 866.565.4410 Clinical.Inquiries@iovance.com

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Locations
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United States, California
University of California San Diego Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
The Angeles Clinic and Research Institute Active, not recruiting
Los Angeles, California, United States, 90048
California Pacific Medical Center Recruiting
San Francisco, California, United States, 94115
United States, Colorado
University of Colorado Cancer Center Recruiting
Aurora, Colorado, United States, 80049
United States, Connecticut
Yale Cancer Center Recruiting
New Haven, Connecticut, United States, 06510
United States, Florida
Mount Sinai Comprehensive Cancer Center Recruiting
Miami Beach, Florida, United States, 33140
University of Florida Health Cancer Center Recruiting
Orlando, Florida, United States, 32806
University of South Florida H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
United States, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States, 46202-5116
United States, Kentucky
James Graham Brown Cancer Center Recruiting
Louisville, Kentucky, United States, 40202
United States, Minnesota
University of Minnesota, Masonic Cancer Center Recruiting
Minneapolis, Minnesota, United States, 55455
United States, New Jersey
Atlantic Health System Recruiting
Morristown, New Jersey, United States, 07960
Rutgers University Terminated
New Brunswick, New Jersey, United States
United States, New York
Roswell Park Cancer Institute Active, not recruiting
Buffalo, New York, United States, 14263
New York University Langone Medical Center Recruiting
New York, New York, United States, 10016
United States, Oregon
Providence Cancer Center Oncology and Hematology Care Clinic Active, not recruiting
Portland, Oregon, United States, 97213
United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19701
University of Pittsburgh Medical Center - Hillman Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
United States, Virginia
Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23298
United States, Wisconsin
Medical College of Wisconsin Active, not recruiting
Milwaukee, Wisconsin, United States, 53226
France
Gustave Roussy Cancer Campus Active, not recruiting
Villejuif Cedex, Ile-de-france, France, 94805
Hôpital Dupuytren Active, not recruiting
Limoges cedex, Limousin, France, 87042
Centre Léon Bérard Active, not recruiting
Lyon, Rhone-alpes, France, 69008
Centre Hospitalier Lyon Sud Active, not recruiting
Pierre-Bénite, Rhone-alpes, France, 69495
Germany
Universitätsklinikum Erlangen Active, not recruiting
Erlangen, Bayern, Germany, 91052
Universitätsklinikum Carl Gustav Carus Active, not recruiting
Dresden, Sachsen, Germany
Hungary
Szegedi Tudomanyegyetem Szent-Györgyi Albert Klinikai Központ Recruiting
Szeged, Csongrad, Hungary, 6720
Semmelweis Egyetem Withdrawn
Budapest, Hungary, 1085
Spain
Clínica Universidad de Navarra Recruiting
Pamplona, Navarra, Spain, 31008
Hospital Universitari Vall d'Hebrón Recruiting
Barcelona, Spain, 08035
Hospital Clinic de Barcelona Recruiting
Barcelona, Spain, 08036
Institut Català d'Oncologia Recruiting
Barcelona, Spain, 08907
Hospital General Universitario Gregorio Marañon Recruiting
Madrid, Spain, 28007
Hospital 12 de Octubre Recruiting
Madrid, Spain, 28041
HM Centro Integral Oncológico Clara Campal Recruiting
Madrid, Spain, 28050
Hospital Universitario Quirónsalud Madrid Recruiting
Madrid, Spain, 28233
Consorci Hospital General Universitari de València Recruiting
Valencia, Spain
Switzerland
Inselspital Recruiting
Bern, Switzerland, 3010
Centre Hospitalier Universitaire Vaudois Lausanne - Centre Pluridisciplinaire d'Oncologie Recruiting
Lausanne, Switzerland
United Kingdom
Addenbrooke's Hospital Active, not recruiting
Cambridge, United Kingdom, CB2 0QQ
Sarah Cannon Research Institute London Active, not recruiting
London, United Kingdom, W1G 6AD
Sponsors and Collaborators
Iovance Biotherapeutics, Inc.
Investigators
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Study Chair: Iovance Biotherapeutics Medical Monitor Iovance Biotherapeutics, Inc.

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Responsible Party: Iovance Biotherapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02360579     History of Changes
Other Study ID Numbers: C-144-01
First Posted: February 10, 2015    Key Record Dates
Last Update Posted: April 3, 2019
Last Verified: April 2019

Keywords provided by Iovance Biotherapeutics, Inc.:
Autologous Adoptive Cell Transfer
Autologous Adoptive Cell Therapy
Cellular Immuno-therapy
Cell Therapy
Tumor Infiltrating Lymphocytes
TIL
LN-144
IL-2
Melanoma
Lifileucel
innovaTIL-01

Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas