Preclinical and clinical studies have shown that adoptive therapy with T cell receptor reactive lymphocytes leads to a clinical response in 13-45% of the patients.
ID
Bron
Verkorte titel
Aandoening
metastasized melanoma
gemetastaseerde huidkanker
Ondersteuning
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
1. Safety (CTCAE 4.0) of the TCR treatment;<br>
2. Objective response rate according to RECIST 1.1.
Achtergrond van het onderzoek
In this study up to 25 patients will be treated with T cell receptor gene therapy. The primary goal of this study is to provide a proof of principle by determining whether autologous T cells modified with a MART-1 specific TCR have sufficient biological activity in advanced stage melanoma patients in terms of classic tumor response. Patients must have had at least 2 lines of therapy before they can be treated in this study.
Doel van het onderzoek
Preclinical and clinical studies have shown that adoptive therapy with T cell receptor reactive lymphocytes leads to a clinical response in 13-45% of the patients.
Onderzoeksopzet
It is a two staged design. First 16 patients will be treated and reviewed. If more than 4 patients responded to the therapy another 9 patients will be treated.
Onderzoeksproduct en/of interventie
Patients will be hospitalized to first receive chemotherapy during one week, then they will receive their own transduced T cells intraveneously, which will be followed by a low-dose of interleukin-2.
Publiek
John B.A.G. Haanen
Amsterdam 1066 CX
The Netherlands
+31 (0)20 5126979
Wetenschappelijk
John B.A.G. Haanen
Amsterdam 1066 CX
The Netherlands
+31 (0)20 5126979
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
1. Patients must be ≥ 18 years of age;
2. Patients must have inoperable stage IIIc or stage IV cutaneous melanoma (AJCC) progressing after at least two lines of therapy (DTIC, BRAF inhibitor, ipilimumab);
3. Patients must be HLA-A*0201 positive;
4. The primary tumor and/or metastasis have to be positive for MART-1 (>10% of tumor cells);
5. Patients with measurable disease (RECIST 1.1);
6. Patients must have a clinical performance status of ECOG 0 or 1;
7. Patients of both genders must be willing to practice a highly effective method of birth control during treatment and for four months after receiving the preparative regimen;
8. Patients must be able to understand and sign the Informed Consent document;
9. Absolute neutrophil count greater than 1.5 x 109/L without support of filgrastim;
10. Platelet count greater than 100 x 109/L;
11. Hemoglobin greater than 5 mmol/L or 8.0 in g/dl;
12. Chemistry;
13. Serum ALAT/ASAT less than 3 times the upper limit of normal, unless patients have liver metastases (< 5 times ULN);
14. Serum creatinine normal range or clearance at 50 ml/min or higher;
15. Total bilirubin less than or equal to 20 micromol/L, except in patients with Gilbert’s Syndrome who must have a total bilirubin less than 50 micromol/L;
16. Seronegative for HIV antibody;
17. Seronegative for hepatitis B antigen, and hepatitis C antibody;
18. Seronegative for lues.
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
1. Life expectancy of less than three months;
2. Patients with metastatic ocular melanoma or mucosal melanoma;
3. Requirement for systemic steroid therapy;
4. Patients who have a history of more than two CNS metastases;
5. Patients who have any CNS lesion that is symptomatic, greater than 1 cm in diameter or show significant surrounding edema on MRI scan will not be eligible until they have
been treated and demonstrated no clinical or radiologic CNS progression for at least 2 months;
6. Any immunosuppressive chemotherapy or systemic steroid therapy within the last 3 weeks;
7. Patients who have: history of coronary revascularization, documented LVEF of less than 45%, clinically significant atrial and/or ventricular arrhythmias including but not limited to atrial fibrillation, ventricular tachycardia, 2° or 3° heart block, documented FEV1 less than or equal to 60% predicted for patients with a history of cigarette smoking (greater than 20 pack/year within the past 2 years) and with symptoms of
respiratory distress;
8. All patients’ toxicities due to prior non-systemic treatment must have recovered to a grade 1 or less. Patients may have undergone minor surgical procedures or focal palliative radiotherapy (to non-target lesions) within the past 4 weeks, as long as all toxicities have recovered to grade 1 or less;
9. Women who are pregnant or breastfeeding, because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. A negative pregnancy test before inclusion in the trial is required for all women of child bearing potential;
10. Any active systemic infections, coagulation disorders or other active major medical illnesses, such as active autoimmune disease requiring anti-TNF treatment.
Opzet
Deelname
Opgevolgd door onderstaande (mogelijk meer actuele) registratie
Geen registraties gevonden.
Andere (mogelijk minder actuele) registraties in dit register
Geen registraties gevonden.
In overige registers
Register | ID |
---|---|
NTR-new | NL3396 |
NTR-old | NTR3539 |
Ander register | NKI-AVL / CCMO : M11TCR / NL37327.000.11; |
ISRCTN | ISRCTN wordt niet meer aangevraagd. |