melanoma skin cancer
Conditions
Interventions
Phase 1, Cohort 1 (n=9): Adding TIL therapy to anti-PD1 immunotherapy. The TIL
will be added 4 weeks after the first nivolumab infusion (on the same day as
the third nivolumab infusions). TIL will b
Sponsors
Academisch Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Age >= 18 years. 2. Histologically or cytologically proven metastatic skin melanoma. 3. Melanoma must be at one of the following AJCC 2009 stages: -Unresectable (or residual) regional metastatic melanoma, i.e. in terms of AJCC 2009 classification unresectable stage III melanoma, or -Stage IV melanoma, i.e. distant metastatic disease (any T, any N, M1a, M1b or M1c), and normal LDH. 4. Patients with brain metastases have to be neurologically stable for at least 2 months and should not use dexamethasone. 5. Presence of measurable progressive disease according to RECIST version 1.1. 6. Expected survival of at least 3 months. 7. WHO performance status = 6,0 mmol/l Granulocytes >= 1,500/µl Lymphocytes >= 700/µl Platelets >= 100,000/µl Creatinine clearance >= 60 min/ml Serum bilirubin
Exclusion criteria
Exclusion criteria: 1. Patients with brain metastases who are neurologically unstable and/or use dexamethasone. 2. Clinically significant heart disease (NYHA Class III or IV). 3. Other serious acute or chronic illnesses, e.g. active infections requiring antibiotics, bleeding disorders, or other conditions requiring concurrent medications not allowed during this study. 4. Active immunodeficiency disease, or autoimmune disease requiring immune suppressive drugs or autoimmune adverse events following treatment with checkpoint inhibitors. Vitiligo is not an exclusion criterion 5. Other malignancy within 2 years prior to entry into the study, except for treated non-melanoma skin cancer and in situ cervical carcinoma. 6. Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study. 7. Lack of availability for follow-up assessments. 8. Pregnancy or breastfeeding. 9. Subjects with a condition requiring systemic chronic steroid therapy (>= 10mg/day prednisone or equivalent) or any immunosuppressive therapy within 14 days prior to planned date for first dose of study treatment. Topical, inhaled, nasal and ophthalmic steroids, and adrenal replacement therapy are allowed. 10. Any serious or uncontrolled medical disorder or active infection that, in the opinion of the investigator, may increase the associated with the participation, study drug administration, or would impair the ability of the patient to receive protocol therapy 11. Known allergy to penicillin or streptomycin (used during the culturing of T cells)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Evaluating the safety and toxicity of first TIL and nivolumab and later of the combination of TIL, PEG-IFNa and nivolumab based on the CTCAE 4.0 criteria. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary objectives include the evaluation of the disease control rate according to RECIST 1.1 criteria and immune response criteria (irRC), progression-free survival (PFS), overall survival (OS), and quality of life. - Potential working mechanisms of the different treatment compounds will be studied in PBMCs of the patients - We will investigate a prognostic biomarker profile while investigating amongst others the blood counts and values, markers on the infused TIL*s, changes in the PBMCs and responses on previous treatments - To find potential differences between the patients that have a clinical response and/or had a clinical response in the past on immunotherapy with immunomonitoring of the infusion T cell product - To determine whether there is a potential correlations between the clinical response and hypothesis related immune parameters in the patient*s tumor material, blood, serum and the TILs used for infusion - To study differences in immunological characteristics between CD8-rich and CD8-poor metastases within a patient detected using CD8-immunoPET/CT, including differences between TIL derived from both locations. - To describe the clinical response to ACT in relation to [89Zr]Zr-crefmirlimab berdoxam uptake on a lesion level. - To study if [89Zr]Zr-crefmirlimab berdoxam uptake in non-affected tissues is related to immune-related adverse events caused by ACT. | — |
Countries
Netherlands
Outcome results
None listed