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

NCT ID: NCT06151847

Condition: Clinical Stage IV Cutaneous Melanoma AJCC v8
Metastatic Melanoma
Pathologic Stage IIIC Cutaneous Melanoma AJCC v8
Unresectable Melanoma

Conditions: Official terms:
Melanoma
Melanoma, Cutaneous Malignant
Skin Neoplasms
Cyclophosphamide
Fludarabine
Interleukin-2
Mitogens

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Procedure
Intervention name: Biospecimen Collection
Description: 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
Arm group label: Treatment (Lifileucel)

Other name: Biological Sample Collection

Other name: Biospecimen Collected

Other name: Specimen Collection

Other name: Undergo blood sample collection

Intervention type: Drug
Intervention name: Cyclophosphamide
Description: Given IV
Arm group label: Treatment (Lifileucel)

Other name: (-)-Cyclophosphamide

Other name: 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate

Other name: Asta B 518

Other name: B-518

Other name: Carloxan

Other name: Ciclofosfamida

Other name: Ciclofosfamide

Other name: Cicloxal

Other name: Clafen

Other name: Claphene

Other name: CP monohydrate

Other name: CTX

Other name: CYCLO-cell

Other name: Cycloblastin

Other name: Cycloblastine

Other name: Cyclophospham

Other name: Cyclophosphamid monohydrate

Other name: Cyclophosphamide Monohydrate

Other name: Cyclophosphamidum

Other name: Cyclophosphan

Other name: Cyclophosphane

Other name: Cyclophosphanum

Other name: Cyclostin

Other name: Cyclostine

Other name: Cytophosphan

Other name: Cytophosphane

Other name: Cytoxan

Other name: Fosfaseron

Other name: Genoxal

Other name: Genuxal

Other name: Ledoxina

Other name: Mitoxan

Other name: Neosar

Other name: Revimmune

Other name: Syklofosfamid

Other name: WR- 138719

Other name: WR-138719

Intervention type: Procedure
Intervention name: Echocardiography
Description: Undergo echocardiography
Arm group label: Treatment (Lifileucel)

Other name: EC

Intervention type: Drug
Intervention name: Fludarabine
Description: Given IV
Arm group label: Treatment (Lifileucel)

Other name: Fluradosa

Intervention type: Biological
Intervention name: Interleukin-2
Description: Given IV
Arm group label: Treatment (Lifileucel)

Other name: Epidermal Thymocyte Activating Factor

Other name: ETAF

Other name: hIL-2

Other name: IL-2

Other name: IL2

Other name: IL2 Protein

Other name: Interleukin 2

Other name: Interleukin 2 Precursor

Other name: Interleukin II

Other name: Lymphocyte Mitogenic Factor

Other name: Mitogenic Factor

Other name: Ro-236019

Other name: T Cell Growth Factor

Other name: T-Cell Growth Factor

Other name: TCGF

Other name: Thymocyte Stimulating Factor

Other name: TSF

Intervention type: Biological
Intervention name: Lifileucel
Description: Given IV
Arm group label: Treatment (Lifileucel)

Other name: Autologous TIL LN-144

Other name: Autologous Tumor Infiltrating Lymphocytes LN-144

Other name: Contego

Other name: Lifileuecel

Other name: LN-144

Intervention type: Procedure
Intervention name: Magnetic Resonance Imaging
Description: Undergo MRI
Arm group label: Treatment (Lifileucel)

Other name: Magnetic Resonance

Other name: Magnetic resonance imaging (procedure)

Other name: Magnetic Resonance Imaging Scan

Other name: Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance

Other name: MR

Other name: MR Imaging

Other name: MRI

Other name: MRI Scan

Other name: NMR Imaging

Other name: NMRI

Other name: Nuclear Magnetic Resonance Imaging

Intervention type: Procedure
Intervention name: Multigated Acquisition Scan
Description: Undergo MUGA scan
Arm group label: Treatment (Lifileucel)

Other name: Blood Pool Scan

Other name: Equilibrium Radionuclide Angiography

Other name: Gated Blood Pool Imaging

Other name: Gated Heart Pool Scan

Other name: MUGA

Other name: MUGA Scan

Other name: Multi-Gated Acquisition Scan

Other name: Radionuclide Ventriculogram Scan

Other name: Radionuclide Ventriculography

Other name: RNVG

Other name: SYMA Scanning

Other name: Synchronized Multigated Acquisition Scanning

Intervention type: Procedure
Intervention name: Tumor Resection
Description: Undergo tumor resection
Arm group label: Treatment (Lifileucel)

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 (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.

Detailed description: PRIMARY OBJECTIVE: I. 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: I. 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: I. 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.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - 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) - 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 Exclusion Criteria: - 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 - 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

Gender: All

Minimum age: 18 Years

Maximum age: 70 Years

Healthy volunteers: No

Locations:

Facility:
Name: University of Kansas Cancer Center

Address:
City: Kansas City
Zip: 66160
Country: United States

Status: Recruiting

Contact:
Last name: Muhammad Umair Mushtaq

Phone: 913-945-6594
Email: mmushtaq@kumc.edu

Contact backup:
Email: kucc-ctotrialref@kumc.edu

Investigator:
Last name: Muhammad Umair Mushtaq
Email: Principal Investigator

Start date: December 21, 2023

Completion date: November 27, 2025

Lead sponsor:
Agency: University of Kansas Medical Center
Agency class: Other

Collaborator:
Agency: National Cancer Institute (NCI)
Agency class: NIH

Collaborator:
Agency: Iovance Biotherapeutics, Inc.
Agency class: Industry

Source: University of Kansas Medical Center

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06151847

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