Adoptive Tumor-infiltrating Lymphocyte Transfer With Nivolumab for Melanoma
Condition: Advanced Melanoma
MeSH terms: Melanoma
Study type: Interventional
Phase: Phase 1

Summary: 
      This study is to investigate safety and feasibility of a combination therapy of a tumor
      infiltrating lymphocytes (TIL) transfer with anti-programmed cell death protein (PD)-1
      therapy in patients with metastatic melanoma that failed immunotherapy.Tumor-infiltrating
      lymphocytes will be expanded from resected melanoma samples from the patient and expanded
      TILs will be transferred to the patient after non-myeloablative chemotherapy with
      cyclophosphamide and fludarabine. TIL transfer will be combined with low dose Interleukin
      (IL)-2 and nivolumab anti-PD-1 treatment.

      The study uses a personalized Investigational Medicinal Product (IMP), i.e. TIL product and
      in combination with IL-2 treatment and nivolumab.
    

Detailed description: 
      Adoptive cell therapy has been previously shown to be an effective treatment option for
      patients with melanoma. Due to an immunosuppressive microenvironment, not all patients
      respond to this therapy. In this trial, the immune suppressive microenvironment will be
      targeted by adding a PD-1 blocking antibody in combination with a TIL Transfer.
      Tumor-infiltrating lymphocytes will be expanded from resected melanoma samples from the
      patient and expanded TILs will be transferred to the patient after non-myeloablative
      chemotherapy with cyclophosphamide and fludarabine. TIL transfer will be combined with low
      dose IL-2 and nivolumab anti-PD-1 treatment. The study uses a personalized IMP, i.e. TIL
      product and in combination with IL-2 treatment and nivolumab.
    

Intervention name(s): Combination of TIL Transfer with anti-PD-1 Therapy and low dose IL-2
Intervention type(s): Drug
Intervention description(s): The study uses a personalized IMP, i.e. TIL product and in combination with IL-2 treatment and nivolumab.
Day 0: Autologous TIL: (minimum 5 x 109 and up to a maximum of 2 x 1011 lymphocytes) administered intravenously over 20 to 30 minutes.
Day 0: Interleukin-2 (Proleukin): 125.000 IU/kg/day s.c. for maximum 12 days as inpatients with a 2 days break after the first 4-5 doses (maximum 10 days dosing). Actual body weight will be used in calculating the dose of interleukin-2.
Starting Day 14: Nivolumab application 240 mg i.v. over 30 minutes ever 2 weeks with a maximum to 2 years, or until disease progression or inacceptable toxicity.
Other intervention name(s): TIL Transfer; anti-PD-1 Therapy Nivolumab; low dose IL-2
Intervention MeSH terms: Nivolumab
Intervention model: Single Group Assignment
Intervention model description: Tumor-infiltrating infiltrate will be expanded from resected melanoma samples from the patient and expanded TILs will be transferred to the patient after non-myeloablative chemotherapy with cyclophosphamide and fludarabine. TIL transfer will be combined with low dose IL-2 and nivolumab anti-PD-1 treatment.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Tumor-infiltrating Lymphocyte (TIL) Transfer; Nivolumab; metastatic melanoma; anti-PD-1 therapy; failed immunotherapy; personalized Investigational Medicinal Product (IMP)