Adoptive TIL therapy plus anti-PD1 in metastatic melanoma

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 25

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. Progressive disease on prior treatment with f.e. BRAF-inhibitors, MEK-inhibitors or immunotherapy, including anti-PD1 treatment. Systemic therapy must have been discontinued for at least four weeks before start of study treatment.

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.
9. Subjects with a condition requiring systemic treatment with either corticosteroids (>10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of treatment. Inhaled or topical steroids and adrenal replacement steroid doses >10mg daily prednisone equivalent are permitted in the absence of active autoimmune disease
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)

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 evaluate the<br /><br>safety and toxicity of TIL and IFN-alpha plus nivolumab according to CTCAE 4.0<br /><br>criteria. Acceptable toxicity is defined as *20% of the patients experiencing<br /><br>serious adverse events as a result of study treatment. </p><br>

Secondary Outcome Measures