Phase II Intratumoral pIL-12 Electroporation in Cutaneous Lymphoma

• Local and distant response rate in patients treated with pIL-12 [ Time Frame: 28 days from day 1 of treatment ] [ Designated as safety issue: No ]

  Patients who complete at least one cycle of treatment are considered evaluable for response. Clinical response will be evaluated and scored every 28 days by the modified SWAT.

  Confirmation of response requires a second assessment after at least 4 weeks. Progression of disease while on treatment should be confirmed by a second assessment 1-4 weeks later.

  
  

• Patient safety when treated with this procedure [ Time Frame: 56 days from day 1 of treatment ] [ Designated as safety issue: Yes ]
  Safety observations and measurements including drug exposure, adverse events, laboratory tests, vital signs, and physical examinations will be documented and reported. Adverse Events will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
  
  
• Progression free survival of patients treated with this procedure [ Time Frame: From Day 1 of treatment to disease progression (estimated up to 6 months) ] [ Designated as safety issue: No ]
  PFS is measured from the date of first treatment to the date of disease progression. It will be calculated using the Kaplan-Meier procedure.
  
  
• Exploratory objective: immune responses in patients treated with pIL-12 [ Time Frame: 28 days from day 1 of treatment ] [ Designated as safety issue: Yes ]

  Examine changes of tumor-infiltrating cells in treated and regressing MF lesions versus stable lesions by immunochemistry staining, as well as anti-tumor elements.

  In addition, also examine peripheral blood to determine the cytokine profile of T cells, as well as NK/T-cell activity pre- and post- treatment with pIL-12 electroporation.

  
  

Patients will receive intra-tumoral injection of pIL-12 at a concentration of 1mg/ml followed immediately by electrical discharge around the tumor site resulting in electroporation of plasmid DNA into tumor cells. The volume of pIL12 used per treatment is in proportion of the total volume of the skin lesions treated, which is calculated as described in Section 6.2. The maximum volume of each treatment (including up to 4 electroporated lesions) per patient is 1 ml and the total volume of pIL12 to be injected is not to exceed 3 ml per cycle. Patients, who do not have progressive disease at non-electroporated sites as judged by modified SWAT or intolerability of the treatment, can receive additional treatment every 3 months for a total of 4 cycles (12 months).

One cycle of treatment consists of three electroporations applied per lesion, to at least two and a maximum of four lesions each day on days 1, 5 and 8 (±1 day). Prior to plasmid injection, using sterile precautions, 1% lidocaine may be injected around the lesion to obtain local anesthesia (prior history of lidocaine hypersensitivity will be assessed prior to administration of local lidocaine injections).

For each cycle, previous untreated sites or previously treated sites that have evidence of persistent disease will be selected as the new electroporation sites.

All grade 3 and 4 toxicities from previous treatments must resolve completely before initiating a new cycle of treatment. Treatment response at untreated sites will be evaluated according to the standard modified SWAT. Response at the electroporated sites will be recoded separately.

Three skin biopsies will be performed during a course of 1 year of treatment. Additional biopsies may be obtained if judged necessary by the treating physician and consented to by the patient.

After the completion of the treatment period of the trial, subjects will be followed for survival at a 6-month interval for a period of 5 years. This follow up period starts after the last scheduled assessment in the treatment period of the study.