Adoptive TIL therapy with low-dose PEG-IFNa plus nivolumab in metastatic melanoma
- Conditions
- melanomaskin cancer10027476
- Registration Number
- NL-OMON56101
- Lead Sponsor
- Academisch Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 58
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 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. Progressive disease on prior treatment with f.e. BRAF-inhibitors,
MEK-inhibitors or immunotherapy, including anti-PD1 treatment. Systemic therapy
with BRAF-/MEK-inhibitors must have been discontinued for at least two weeks
before start of study treatment. Treatment with immunotherapy must have been
discontinued for at least four weeks before start of study treatment.
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)
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Evaluating the safety and toxicity of first TIL and nivolumab and later of the<br /><br>combination of TIL, PEG-IFNa and nivolumab based on the CTCAE 4.0 criteria. </p><br>
- Secondary Outcome Measures
Name Time Method