Metastatic melanoma
Conditions
Interventions
Product Name: Tumor Infiltrating T-cells
Product Code: TIL
Pharmaceutical Form: Infusion
INN or Proposed INN: Tumor infiltrating lymphocytes
Current Sponsor code: TIL
Other descriptive name: AUTOLOGOU
Sponsors
Leiden University Medical Center
Eligibility
Sex/Gender
All
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 =1. 8. Within the last 2 weeks prior to study day 1, vital laboratory parameters should be within normal range, except for the following laboratory parameters, which should be within the ranges specified : Lab Parameter Range Hemoglobin = 6,0 mmol/l Granulocytes = 1,500/µl Lymphocytes = 700/µl Platelets = 100,000/µl Creatinine clearance = 60 min/ml Serum bilirubin = 40 mol/l ASAT and ALAT = 5 x the normal upper limit LDH = 2 x the normal upper limit 9. Viral tests: -Negative for HIV type 1/2, HTLV and TPHA -No HBV (hepatitis B virus) antigen or antibodies against HBc in the serum -No antibodies against HCV (hepatitis C virus) in the serum 10. Able and willing to give valid written informed consent. 11. Prior treatment is allowed, including anti-PD1 treatment, but systemic therapy must have been discontinued for at least four weeks before study entry. Radiotherapy and targeted therapy should be discontinued for at least two weeks before study entry. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. Patients with brain metastases who are neurologically unstable and/or on use of 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. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and toxicity of ACT plus nivolumab according to CTCAE 4.0 criteria. ;Secondary Objective: Evaluation of the clinical response according to RECIST 1.1 criteria and immune related response criteria (irRC) and overall survival (OS). ;Primary end point(s): The study is stopped when at least 3 patients experience treatment limiting toxicity. ;Timepoint(s) of evaluation of this end point: The study is stoppend when at least 3 patients experience treatment limiting toxicity. If no treatment limiting toxicity occurs the primary endpoint is evaluated after completing treatment of 10 patients, which is anticipated to be finalized 3-4 years after initiation of the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): There is an interim analysis of the secondary objective after treatment of 15 patients. The study is stopped when after treating 15 patients less than 2 patients show clinical benefit (defined as CR, PR or SD according to RECIST 1.1) ;Timepoint(s) of evaluation of this end point: The clinical response is evaluated and stopped when after completing treatment of 15 patients less than 2 patients who clinical benefit. This evaluation is anticipated to be finalized 4 years after initiation of the study. If at least 2 of the 15 patients show clinical benefit the study enters the second stage (Simon's two stage approach) and a maximum of 25 patients will be included for final evaluation of the secondary endpoint and of additional immune related parameters. | — |
Countries
Netherlands
Contacts
Public ContactClinical Oncology
Leiden University Medical Center
Outcome results
None listed