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Clinical Stage IV Cutaneous Melanoma AJCC v8Phase 2NCT06151847

Lifileucel With Reduced Dose Fludarabine/Cyclophosphamide Lymphodepletion and Interleukin-2 for the Treatment of Patients With Unresectable or Metastatic Melanoma

A Phase 2 study testing Biospecimen Collection, Cyclophosphamide and Echocardiography in people with Clinical Stage IV Cutaneous Melanoma AJCC v8 and Metastatic Melanoma, run by University of Kansas Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This phase II trial tests how well lifileucel, with reduce dose fludarabine and cyclophosphamide for lymphodepletion and interleukin-2, work for treating patients with melanoma that cannot be removed by surgery (unresectable) or that has spread from where it first started (primary site) to other places in the body… Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Biospecimen Collection, Cyclophosphamide and Echocardiography
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
1 siteUnited States
Study dates
21 Dec 2023to 10 Jul 2025
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 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Males and females age ≥ 18 years Enrollment of patients ≥ 70 years of age may be allowed at principal investigator discretion.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
  • At least one measurable target lesion, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
  • 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 lesion
  • Women of childbearing potential must have a negative serum pregnancy test 48 hours prior to initiating treatment
  • Patients with unresectable or metastatic melanoma (stage IIIc or stage IV)
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  • Patients must have progressed following 1-3 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 mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor
  • 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)
  • Adequate hematologic and organ function
  • Patients must have recovered from all prior therapy-related adverse events (AEs) to ≤ grade 1 (per Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5.0), except for alopecia or vitiligo, prior to enrollment (tumor resection)
  • Patients with documented ≥ grade 2 diarrhea or colitis because 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
  • Patients with immunotherapy-related endocrinopathies stable for at least 6 weeks (eg, hypothyroidism), and controlled with hormonal replacement (non-corticosteroids), are allowed
  • Patients must have a washout period of ≥ 28 days from prior anticancer therapy(ies) to the start of the planned reduced dose lymphodepletion (RDL) preconditioning regimen:
  • Targeted therapy: MEK/BRAF or other targeted agents
  • Chemotherapy
  • Immunotherapy: anti-CTLA-4/anti-PD-1, other monoclonal antibodies (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 v 5.0
  • Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence or to use the forms of contraception listed in Child-Bearing Potential/Pregnancy section for the duration of study participation and for 12 months following the last dose of IL-2 or until the first dose of the next anti-cancer therapy, whichever occurs first

Who cannot join

  • Current or anticipating use of other anti-neoplastic or investigational agents while participating in this study
  • Is pregnant or breastfeeding
  • Patients who have active medical illness(es) that would pose increased risk for study participation, including active systemic infections requiring systemic antibiotics, coagulation disorders, or other active major medical illnesses of the cardiovascular, respiratory, or immune system
  • 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
  • Patients who have received an organ allograft or prior cell transfer therapy
  • Patients with melanoma of uveal/ocular origin
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  • Patients who have a history of hypersensitivity to any component or excipient of Lifileucel or other study drugs
  • Patients who have any form of primary immunodeficiency (such as severe combined immunodeficiency disease [SCID] and acquired immunodeficiency syndrome [AIDS])
  • Patients who have a left ventricular ejection fraction (LVEF) < 45% or New York Heart Association (NYHA) functional classification class > 1
  • Patients who have a documented forced expiratory volume in 1 second (FEV1) of ≤ 60%
  • Patients who have had another primary malignancy within the previous 3 years (except for carcinoma in situ of the breast, cervix, or bladder; localized prostate cancer; and non-melanoma skin cancer that has been adequately treated)
  • Patients with symptomatic and/or untreated brain metastases (of any size and any number)
  • Other protocol defined inclusion/exclusion criteria could apply

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

Other trials in United States

About this study

Official title: Reduced Dose Fludarabine/Cyclophosphamide Lymphodepletion Before Tumor-Infiltrating Lymphocyte Therapy With Lifileucel in Metastatic Melanoma

This phase II trial tests how well lifileucel, with reduce dose fludarabine and cyclophosphamide for lymphodepletion and interleukin-2, work for treating patients with melanoma that cannot be removed by surgery (unresectable) or that has spread from where it first started (primary site) to other places in the body (metastatic).Lifileucel 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. Giving Lifileucel with a reduced dose of fludarabine and cyclophosphamide for lymphodepletion and interleukin -2 is being studied in patients with unresectable or metastatic melanoma.

Read the detailed description

PRIMARY OBJECTIVE:

  1. The percentage of total TIL clones as measured by the T-cell receptor (TCR) population shared between the tumor infiltrating lymphocyte (TIL) product and peripheral blood mononuclear cells (PBMC).

SECONDARY OBJECTIVES:

  1. To evaluate the efficacy parameters of lifileucel (LN-144) in combination with a reduced dose lymphodepletion in patients with unresectable or metastatic melanoma by assessing objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

II. To characterize the safety profile of lifileucel (LN-144) in combination with a reduced dose lymphodepletion regimen in patients with unresectable or metastatic melanoma.

EXPLORATORY OBJECTIVE:

  1. Blood and tumor samples will be banked for future correlative analyses, including flow cytometry, next generation sequencing, immunogenomics and RNA sequencing to characterize the immunome and microenvironment.

OUTLINE:

Patients undergo tumor resection surgery. After the lifileucel is manufactured (approximately 4 weeks later), patients receive cyclophosphamide intravenously (IV) on days -4 to -2 and fludarabine IV on days -4 to -1. Patients then receive lifileucel IV on day 0. Patients also receive up to 6 doses of intraleukin-2 IV.

After completion of study treatment, patients are followed up at day 28, 42, 84, 126, 180, 365, month 18, and month 24.

Being tested
Biospecimen Collection, Cyclophosphamide, Echocardiography, Fludarabine, Interleukin-2
Medical subject headings
Melanoma

What participants receive

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

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection, Undergo blood sample collection

    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

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B-518

    Given IV

  • EchocardiographyProcedure or surgery

    Also called EC

    Undergo echocardiography

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • Interleukin-2Biological

    Also called Epidermal Thymocyte Activating Factor, ETAF, hIL-2, IL-2

    Given IV

  • LifileucelBiological

    Also called Autologous TIL LN-144, Autologous Tumor Infiltrating Lymphocytes LN-144, Contego, Lifileuecel

    Given IV

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance

    Undergo MRI

  • Multigated Acquisition ScanProcedure or surgery

    Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan

    Undergo MUGA scan

  • Tumor ResectionProcedure or surgery

    Undergo tumor resection

Study groups in NCT06151847
Study groupRoleWhat they receive
Treatment (Lifileucel)ExperimentalLifileucel (LN-144) is an autologous Tumor Infiltrating Lymphocytes (TIL) cell therapy. A tumor sample is resected from each patient for lifileucel manufacturing. Patients then receive the lifileucel regimen which consists of a reduced dose non-myeloablative lymphodepletion, lifileucel infusion followed by interleukin-2.
Receives: Procedure: Biospecimen Collection; Drug: Cyclophosphamide; Procedure: Echocardiography; Drug: Fludarabine; Biological: Interleukin-2; Biological: Lifileucel; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Procedure: Tumor Resection

What is being measured

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

  1. Percentage of total T-cell receptor (TCR) populations shared between the TIL product and peripheral blood mononuclear cells (PBMCs)

    The TCR population is calculated as the frequencies of unique CDR3 sequences as measured by HTBIvc assay. Will be summarized with respect to mean and standard deviation. The percentage changes will also be presented with respect to visual diagrams for each person, e.g., waterfall plot

    Measured: At day + 42

Secondary outcomes (7)

  1. Safety: Incidence of treatment emergent adverse events

    Defined as all grades and any attribution until day 28 (EOT visit) after infusion, grade 3-4 of any attribution from day 28 to 6 months, only grade 3-4 attributed to study drugs after 6 months evaluated by Common Terminology Criteria in Adverse Events (CTCAE). Will be presented as percentage with 95% confidence intervals and tabulated by type and grade.

    Measured: From start of treatment to 6 months after TIL

  2. Safety: Incidence of serious adverse events

    Defined as all grades and any attribution until day 28 (EOT visit) after infusion, grade 3-4 of any attribution from day 28 to 6 months, only grade 3-4 attributed to study drugs after 6 months evaluated by CTCAE. Will be presented as percentage with 95% confidence intervals and tabulated by type and grade.

    Measured: From start of treatment to 6 months after TIL

  3. Transfusion requirements

    Defined as all grades and any attribution until day 28 (EOT visit) after infusion, grade 3-4 of any attribution from day 28 to 6 months, only grade 3-4 attributed to study drugs after 6 months evaluated by CTCAE. Will be presented as percentage with 95% confidence intervals and will be summarized with respect to mean and standard deviation.

    Measured: From start of treatment to 6 months after TIL

  4. Length of hospital stay

    Defined as all grades and any attribution until day 28 (EOT visit) after infusion, grade 3-4 of any attribution from day 28 to 6 months, only grade 3-4 attributed to study drugs after 6 months evaluated by CTCAE. Will be presented as percentage with 95% confidence intervals and will be summarized with respect to mean and standard deviation.

    Measured: From start of treatment to 6 months after TIL

  5. Overall response rate

    Measured by Response Evaluation Criteria in Solid Tumor (RECIST) 1.1. Will be presented as percentage with 95% confidence internal using Clopper-Pearson Exact method.

    Measured: From start of treatment until the end of treatment, up to 2 years

  6. Progression free survival

    Will be summarized with Kaplan-Meir curves and estimation of medians with 95% confidence intervals.

    Measured: From start of treatment until objective tumor progression or death, up to 2 years

  7. Overall survival

    Will be summarized with Kaplan-Meir curves and estimation of medians with 95% confidence intervals.

    Measured: From start of treatment to death due to any cause, up to 2 years

Timeline

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

  1. First posted30 Nov 2023
  2. Study start21 Dec 2023
  3. Primary completion10 Jul 2025
  4. Study completion10 Jul 2025

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
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06151847
Sponsor's protocol ID
STUDY00150697
Other IDs
NCI-2023-09309, IIT-2022-LDTIL, STUDY00150697, P30CA168524
Status last verified
Apr 2026
First submitted
17 Nov 2023
Last updated
30 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Mushtaq MU, Abdelhakim H, Selby L, Shahzad M, Abhyankar SH, McGuirk JP, Doolittle GC. Reduced dose fludarabine and cyclophosphamide lymphodepletion before tumor-infiltrating lymphocyte therapy in melanoma. Future Oncol. 2025 Jun;21(13):1631-1637. doi: 10.1080/14796694.2025.2498842. Epub 2025 May 9.

    PubMed 40343719

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