HAITILS: Hepatic Arterial Infusion of Autologous Tumor Infiltrating Lymphocytes in Patients With Melanoma and Liver Metastases

Sponsor

Vastra Gotaland Region (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04812470

Collaborator

Miltenyi Biomedicine GmbH (Industry)

Enrollment

Arm

76.9

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the feasibility, safety and tolerability of treatment with autologous tumor infiltrating lymphocytes (TIL) administered via hepatic arterial infusion in patients with liver metastases (including but not restricted to) of malignant melanoma.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Uveal Melanoma Metastatic Cutaneous Melanoma	Drug: Autologous Tumor Infiltrating Lymphocytes Drug: Melphalan Drug: Interleukin-2	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

6 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Intervention Model Description:

dose escalationdose escalation

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study Using Hepatic Arterial Infusion of Autologous Tumor Infiltrating Lymphocytes in Patients With Melanoma and Liver Metastases

Anticipated Study Start Date :

Nov 1, 2021

Anticipated Primary Completion Date :

Mar 31, 2023

Anticipated Study Completion Date :

Mar 31, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Autologous tumor infiltrating lymphocytes (TIL) Autologous TIL administered via hepatic arterial infusion followed by low dose Interleukin-2 after preconditioning chemotherapy with Melphalan.	Drug: Autologous Tumor Infiltrating Lymphocytes Administered via hepatic arterial infusion Drug: Melphalan Melphalan will be administered once as an intravenous infusion. Drug: Interleukin-2 After TIL infusion, Interleukin-2 will be administered subcutaneously once daily for up to 14 days.

Arm

Intervention/Treatment

Experimental: Autologous tumor infiltrating lymphocytes (TIL)

Autologous TIL administered via hepatic arterial infusion followed by low dose Interleukin-2 after preconditioning chemotherapy with Melphalan.

Drug: Autologous Tumor Infiltrating Lymphocytes

Administered via hepatic arterial infusion

Drug: Melphalan

Melphalan will be administered once as an intravenous infusion.

Drug: Interleukin-2

After TIL infusion, Interleukin-2 will be administered subcutaneously once daily for up to 14 days.

Outcome Measures

Primary Outcome Measures

Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) [5 years from start of chemotherapy]
Adverse events are graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0

Secondary Outcome Measures

Objective response rate (ORR) [2 years from start of chemotherapy]
Defined by RECIST 1.1
Clinical benefit rate (CBR) [18 weeks]
Defined by RECIST 1.1
Progression free survival (PFS) [2 years]
Evaluation of progression-free survival
hepatic Progression free survival (hPFS) [2 years]
Evaluation of hepatic progression-free survival
Duration of objective response (DOR) [2 years]
Evaluation of duration of response
Overall Survival (OS) [5 years]
Evaluation of overall survival
Evaluation of feasibility of an automated production of TILs [2 years]
Defined as the proportion of patients included that receive treatment with the TIL product.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients ≥18 years of age on the day of signing informed consent.
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

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) or Magnetic Resonance Imaging (MRI) 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.
Eastern Cooperative Oncology Group performance status of 0 - 2.
Female patient of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
Female patients of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
Male patients of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

Exclusion Criteria:

Life expectancy of less than 3 months.
History of interstitial lung disease (ILD) or (non-infectious) pneumonitis.
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.
History of severe hypersensitivity reactions to monoclonal antibodies.
Active infection.
Known human immunodeficiency virus (HIV) infection, acquired immunodeficiency syndrome (AIDS), hepatitis B or hepatitis C.
Active autoimmune disease or a history of known or suspected 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.
Pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study drug.
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