Phase II Intratumoral IL12 Plasmid Electroporation in Cutaneous Lymphoma
Condition: Cutaneous T Cell Lymphomas (CTCL); Mycosis Fungoides (MF)
MeSH terms: Mycoses; Lymphoma; Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous
Intervention: Tavokinogene Telseplasmid (tavo); OncoSec Medical System (OMS)
Intervention description: Patients received intratumoral injection(s) of tavo.; Electroporation via OMS was performed immediately following intratumoral injection of tavo. A sterile applicator containing 6 stainless steel electrodes arranged in a circle were placed around the tumor. The applicator was connected to the OMS power supply and six pulseswere administered to each tumor lesion at the approximate point of tavo injection.
Intervention MeSH terms: Interleukin-12
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      A single arm, open label, multi-center, phase 2 study to assess the safety and anti-tumor
      activity of ImmunoPulse IL-12® in participants with stage IB to IIIB mycosis fungoides.
      ImmunPulseIL12® is the combination of intrtumoral interleukin-12 gene (also known as
      tavokinogene telseplasmid [tavo]) and in vivo electroporation-mediated plasmid
      deoxyribonucleic acid [DNA] vaccine therapy (tavo-EP) administered using the OncoSec Medical
      System (OMS).

      All participants may receive up to four cycles of treatment consisting of three treatment
      days, Days 1, 5 and 8, in a 12-week cycle as per Protocol version 6 (see Limitations and
      Caveats section of this record for protocol version information). Patients will receive
      intra-tumoral injection of tavo at a concentration of 1.0 mg/mL (maximum volume of 1 mL/day
      distributed over 2-4 lesions), followed immediately by electrical discharge around the tumor
      site resulting in electroporation of plasmid deoxyribonucleic acid (DNA) into tumor cells.
    

Eligibility criteria:

        Inclusion Criteria

          1. Biopsy confirmed mycosis fungoides of stage IB - IIIB;

          2. Participants must have failed or have been intolerant to at least one standard of care
             therapy;

          3. Participants must have a minimum of one lesion, or affected area in erythrodermic
             patients (T4/stage III), that meets all following criteria:

               -  Accessible for pIL-12 electroporation;

               -  Adequate size such that 6-mm biopsy can be collected prior to treatment;

          4. Participants must have one additional lesion, or affected area in erythrodermic
             patients, that remains untreated for the duration of the study;

          5. Age ≥ 18 years old;

          6. Participants must have Eastern Cooperative Oncology Group (ECOG) performance status
             0-2;

          7. Required wash out period of 4 weeks from last dose for the following prior therapies:

               -  Topical therapy;

               -  Radiotherapy (including photo therapy);

               -  Multi-agent chemotherapy;

               -  Systemic biological therapy;

               -  Histone deacetylase inhibitors (HDAC) inhibitors;

               -  Interferon alpha and other investigational therapies;

          8. For women of childbearing potential, negative pregnancy serum test within 14 days to
             the first study drug administration, and use of birth control from 30 days prior to
             the first day study drug administration and 30 days following last day study drug
             administration;

          9. Male participants must be surgically sterile, or must agree to use contraception
             during the study and at least 30 days following the last day of study drug
             administration.

         10. Life expectancy of at least 6 months;

         11. The patient must have adequate renal and hepatic function as assessed by standard
             laboratory criteria within 4 weeks prior to enrollment:

               -  Creatinine < 2 x upper limit of normal (ULN);

               -  Serum bilirubin within institutional normal limits;

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 1.5 x ULN;

               -  Absolute neutrophil count (ANC) > 1000/mm;

               -  Platelet count > 100,000 /mm;

         12. Able to give informed consent and able to follow guidelines given in the study.

        Exclusion Criteria

          1. Prior therapy with IL-12 or prior gene therapy;

          2. Prior treatment with Campath (alemtuzumab) within 1 year of enrollment;

          3. Concurrent immunotherapy, chemotherapy, or radiation therapy for duration of patient
             participation on study;

          4. Concurrent steroid therapy;

          5. Concurrent anticoagulant therapy (acetylsalicylic acid [ASA]≤ 325mg/day allowed);

          6. Evidence of significant active infection (e.g., pneumonia, cellulitis, wound abscess,
             etc.) at time of study enrollment;

          7. Patients with current evidence of large cell transformation (LCT) with aggressive
             disease at study entry (patients with a history of LCT are eligible if pathologic
             evidence at study entry indicates there is no presence of LCT);

          8. Known history of human immunodeficiency virus (HIV), Human T-cell leukemia virus
             (HTLV) -1/2 infection, hepatitis B or hepatitis C (active, prior treatment, or both);

          9. No other prior malignancy is allowed except for the following: adequately treated
             basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
             Stage I or II cancer from which the patient is currently in complete remission, or any
             other cancer from which the patient has been disease-free for 2 years;

         10. Significant cardiovascular disease (i.e. New York Heart Association [NYHA] class 3
             congestive heart failure; myocardial infarction within the past 6 months; unstable
             angina; coronary angioplasty with the past 6 months; uncontrolled atrial or
             ventricular cardiac arrhythmias);

         11. Any other medical history, including laboratory results, deemed by the investigator to
             be likely to interfere with patient's participation in the study, or to interfere with
             the interpretation of the results;

         12. Participants with electronic pacemakers or defibrillators are excluded from this study
             as the effect of electroporation on these devices is unknown;

         13. Pregnant and breast-feeding women are excluded from the study as effects on the fetus
             are unknown and there may be a risk of increased fetal wastage.