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