Locoregional Administration of TIL and Lymphodepletion in Patients With Melanoma and Liver Metastases

NCT05903937 | Not Yet Recruiting Phase 1

• 1 other identifier: 2023-006126-32
• Study Type: interventional
• Target: 6
• Locations: 0 countries
• Sites: N/A

Brief Summary

Evaluate the safety and tolerability of treatment with autologous tumor infiltrating lymphocytes (TIL) administered via hepatic arterial infusion and preconditioning with percutaneous hepatic perfusion in patients with liver metastases (but not restricted to) of malignant melanoma

Conditions

Uveal Melanoma; Metastatic Cutaneous Melanoma

Keywords

TIL; ACT; PHP

Outcome Measures

Primary Outcomes (1)

• Incidence and severity of adverse events

  Graded according to Common Terminology Criteria for Adverse Events version 5.0

  5 years

Secondary Outcomes (6)

• Objective response rate

  5 years

• Progression-free survival

  5 years

• hepatic Progression-free survival

  5 years

• Duration of response

  5 years

• Overall survival

  5 years

Study Arms (1)

Autologous tumor infiltrating lymphocytes (TIL)

EXPERIMENTAL

Drug: Autologous Tumor Infiltrating Lymphocytes; Drug: Melphalan; Drug: Interleukin-2

Interventions

Autologous Tumor Infiltrating Lymphocytes DRUG

Administered via hepatic arterial infusion (HAI)

Autologous tumor infiltrating lymphocytes (TIL)

Melphalan DRUG

Administered via isolated hepatic perfusion

Autologous tumor infiltrating lymphocytes (TIL)

Interleukin-2 DRUG

low-dose, administered s.c.

Autologous tumor infiltrating lymphocytes (TIL)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is willing and able to provide written informed consent and comply with study procedures. Written informed consent must be signed and dated before the start of specific protocol procedures.
• Patient must have a histologically/cytologically confirmed diagnosis of:
• stage IV uveal melanoma with or without any previous systemic therapy OR
• stage IV cutaneous melanoma with confirmed progression following at least one or two prior systemic therapies including a programmed cell death protein-1 (PD-1) inhibitor with or without a CTLA-4 inhibitor; and if BRAF V600 mutation-positive, also a BRAF inhibitor or a BRAF inhibitor in combination with a MEK inhibitor.
• Measurable disease by computed tomography (CT) per RECIST 1.1 criteria with at least one target lesion identified in the liver and where the distribution pattern of metastasis is predominantly engaging the liver as judged by the investigator.
• At least one resectable lesion in the liver (or aggregate of lesions resected) of a minimum size of 0.5 cm in diameter post- resection to generate TILs.
• ECOG performance status of 0 - 1.

You may not qualify if:

• Life expectancy of less than 3 months.
• Reduced renal function defined as S-Creatinine \>=1.5xULN or Creatinine Clearance \< 40 mL/min, calculated using the Cockroft and Gault formula.
• Reduced hepatic function (defined as ASAT, ALAT, bilirubin \> 3\*ULN and PK- INR \> 1.5) or medical history of liver cirrhosis or portal hypertension.
• Hemoglobin \<90 g/L or platelets \<100x109/L or neutrophils \<1.5x109/L
• Use of live vaccines four weeks before or after the start of study.
• Infection of human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS), hepatitis B or hepatitis C.
• Active autoimmune disease.
• A condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \>10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Concomitant therapy with any other anti- cancer therapy, concurrent medical conditions requiring use of immunosuppressive medications or use of other investigational drugs.
• Has a known additional malignancy of other diagnosis that is progressing or requires active treatment.
• A history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator

Sponsors & Collaborators

• Vastra Gotaland Region: lead

MeSH Terms

Conditions

Uveal Melanoma; Melanoma

Interventions

Melphalan; Interleukin-2

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Lymphokines; Proteins; Biological Factors

Central Study Contacts

Lars Ny

CONTACT

+46 31 342 10 00; lars.ny@vgregion.se

Axel Nelson

CONTACT

axel.nelson@vgregion.se

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2023
• First Posted: June 15, 2023
• Study Start: December 31, 2023
• Primary Completion: December 31, 2024
• Study Completion (Estimated): December 31, 2029
• Last Updated: June 15, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share