NCT02654821

Study With T-cel Receptor Gene Therapy in Metastatic Melanoma

Multicenter Phase I/IIa Study Using T-cell Receptor Gene Therapy in Metastatic Melanoma

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: The Netherlands Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Patients with stage IV melanoma (also eye melanoma) will be treated with TCR transduced cells.

Detailed description

In this multicenter phase I/IIa trial 25 patients will be treated with non-myeloablative chemotherapy followed by adoptive transfer of autologous TCR transduced T cells, to study the feasibility, safety and efficacy of this treatment. Patients will receive a non-myeloablative lymphocyte-depleting preparative regimen consisting of cyclophosphamide (60 or 30 mg/kg/day x 2 days i.v.) and fludarabine (25 mg/m2/day i.v. x 5 days). Following this regimen, patients will receive one single intravenous adoptive transfer of transduced T cells starting with the first dose level. * Dose level 1: 5x10\^7 transduced T cells, cyclophosphamide 60 mg/kg/day * Dose level 1a: 1,0x10\^8 transduced T cells, cyclophosphamide 30 mg/kg/day * Dose level 2: 2,5x10\^8 transduced T cells, cyclophosphamide 60 mg/kg/day * Dose level 3: maximum 1x10\^9 transduced T cells (depending on production yield). At time points 4, 8, and 12 weeks and every 3 months thereafter patients will be evaluated for response to treatment. After 3 patients have been treated in each dose level, but not before 8 weeks after the last patient has been infused with transduced T cells, the DSMB will be informed about the observed toxicity and efficacy within this cohort and decide, based on this information, whether the trial will be continued to the next dose level or will continue in the current dose level. The study will continue as the first stage (2-stage Simon), until a total of 16 patients have been enrolled and treated: if less than 2 responses are observed, the trial will be stopped and the conclusion will be that TCR lacks efficacy. Otherwise, the trial will continue its second stage. In addition, safety data after these first 16 patients will be evaluated by the DSMB. Any unexpected or serious (grade 3/4 or higher) toxicities during the trial, will be reported immediately to the DSMB and CCMO. Second stage: overall 25 patients will be enrolled (including the first stage): if the total number of responses for the two stages combined is less than 5, the trial will be stopped as soon as this is evident and the conclusion will be that TCR lacks efficacy.

Conditions

• Stage IV Skin Melanoma
• Eye; Melanoma

Interventions

Type	Name	Description
BIOLOGICAL	TCR transduced T-cells	Eligible patients will undergo leukapheresis to isolate autologous T cells. These T cells will be transduced with a retroviral vector encoding the 1D3 HM CysTCR, and subsequently expanded during short-term ex vivo culture. Following pre-treatment with nonmyeloablative chemotherapy, patients will receive the adoptive transfer of autologous, TCR transduced T cells.
PROCEDURE	Biopsy	During screening, after treatment and at time of regression/progression a biopsy will be taken for translational research.
PROCEDURE	Blood taking	During screening, after the infusion with T-cells, after treatment and at time of regression/progression blood will be taken for translational research.

Timeline

• Start date: 2012-03-01
• Primary completion: 2019-10-01
• Completion: 2020-01-01
• First posted: 2016-01-13
• Last updated: 2018-11-02

Locations

1 site across 1 country: Netherlands