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This is a multicentric study in which metastatic melanoma patients that have already been treated with at least 2 therapies, will be treated with their own white blood cells that are genetically transduced.


- candidate number13168
- NTR NumberNTR3539
- ISRCTNISRCTN wordt niet meer aangevraagd.
- Date ISRCTN created
- date ISRCTN requested
- Date Registered NTR27-jul-2012
- Secondary IDsM11TCR / NL37327.000.11; NKI-AVL / CCMO
- Public TitleThis is a multicentric study in which metastatic melanoma patients that have already been treated with at least 2 therapies, will be treated with their own white blood cells that are genetically transduced.
- Scientific TitleMulticenter phase I/IIa study using T-cell receptor gene therapy in metastatic melanoma.
- ACRONYMTCR
- hypothesisPreclinical 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.
- Healt Condition(s) or Problem(s) studiedMetastasized melanoma
- Inclusion criteria1. 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.
- Exclusion criteria1. 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.
- mec approval receivedyes
- multicenter trialyes
- randomisedno
- groupParallel
- TypeSingle arm
- Studytypeintervention
- planned startdate 1-apr-2012
- planned closingdate1-apr-2015
- Target number of participants25
- InterventionsPatients 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.
- Primary outcome1. Safety (CTCAE 4.0) of the TCR treatment;
2. Objective response rate according to RECIST 1.1.
- Secondary outcome1. 1-year progression free survival (PFS) and median overall survival;
2. Efficacy of induction of tumor specific T cell responses (as measured by the persistence of Melan-A/MART1 specific T cells in peripheral blood samples at several time points following adoptive transfer and in tumor biopsies when possible).
- TimepointsIt 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.
- Trial web siteN/A
- statusopen: patient inclusion
- CONTACT FOR PUBLIC QUERIESProf. Dr. John B.A.G. Haanen
- CONTACT for SCIENTIFIC QUERIESProf. Dr. John B.A.G. Haanen
- Sponsor/Initiator Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (NKI AVL)
- Funding
(Source(s) of Monetary or Material Support)
Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (NKI/AVL)
- PublicationsN/A
- Brief summaryIn 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.
- Main changes (audit trail)
- RECORD27-jul-2012 - 11-aug-2012


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