Adoptive T cell therapy plus vaccination in metastatic melanoma patients

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 25

Inclusion Criteria

1. Age >= 18 years.
2. Histologically proven melanoma.
3. Melanoma must be at one of the following AJCC 2009 stages:
-Irresectable (or residual) regional metastatic melanoma, i.e. in terms of AJCC 2009 classification irresectable 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 µmol/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, including immunotherapy e.g. with Ipilimumab, is allowed but systemic therapy must have been discontinued for at least four weeks before study entry. Radiotherapy and MEK-inhibitor/BRAF-inhibitor should be discontinued for at least two weeks before study entry. Patients should have PD after treatment. After treatment with Ipilimumab initial PD should be confirmed by repeated imaging studies evaluated according to irRC to exclude late effects of Ipilimumab treatment.

Exclusion Criteria

Patients will be excluded from the study for any of the following reasons:;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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objective of this phase I/II clinical trial is to demonstrate the<br /><br>feasibility and to evaluate the safety and toxicity of ACT plus vaccination<br /><br>according to CTCAE 4.0 criteria. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>The secondary objective of this study is the evaluation of a clinical response<br /><br>according to RECIST 1.1 and overall survival (OS). Clinical benefit is defined<br /><br>as Stable Disease (SD), Partial Response (PR), or Complete response (CR).<br /><br>An additional endpoint is to determine the induced immune response in patient*s<br /><br>blood and serum and in the T cells used for infusion.</p><br>