Phase II Intratumoral IL12 Plasmid Electroporation in Cutaneous Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
OncoSec Medical Incorporated
ClinicalTrials.gov Identifier:
NCT01579318
First received: April 15, 2012
Last updated: June 15, 2015
Last verified: June 2015
  Purpose

A single arm, open label, multi-center, phase 2 study to assess the safety and anti-tumor activity of intratumoral IL-12 plasmid (i.e., pIL-12) electroporation in subjects with stage IB to IIIB mycosis fungoides.

All subjects may receive up to six cycles of treatment consisting of two treatment days, Days 1 and 8, in a 28-day cycle. Patients will receive intra-tumoral injection of pIL-12 at a concentration of 0.5mg/ml and a fixed volume of 0.25 mL per each 1.0 cm diameter of target region, followed immediately by electrical discharge around the tumor site resulting in electroporation of plasmid DNA into tumor cells.


Condition Intervention Phase
Cutaneous T Cell Lymphomas (CTCL)
Mycosis Fungoides (MF)
Drug: IL-12 plasmid (pIL-12)
Device: Electroporation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter Phase II Trial of Intratumoral IL12 Plasmid Electroporation in Cutaneous Lymphoma

Resource links provided by NLM:


Further study details as provided by OncoSec Medical Incorporated:

Primary Outcome Measures:
  • objective response rate by modified Severity Weighted Assessment Tool (mSWAT) in the skin score and the composite global score [ Time Frame: within 24 weeks of first treatment ] [ Designated as safety issue: No ]
    To assess the objective response rate by modified Severity Weighted Assessment Tool (mSWAT) in the skin score and the composite global score (skin, lymph nodes, blood and viscera) within 24 weeks of first treatment.


Secondary Outcome Measures:
  • Patient safety when treated with this procedure [ Time Frame: 2 years ] [ 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

  • Duration of overall objective response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Duration of overall objective response (CR or PR) is the number of days from the initial documentation of an objective response to the most current evaluation of that response or to documentation of progression.

  • Time to overall objective response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Time to overall objective response (CR or PR) is the number of days from the start of therapy to the first documentation of objective response.

  • Immunologic effects of IL-12 plasmid electroporation in tissue [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    1. Transcriptional analysis of interferon pathway activation, antigen presentation and processing machinery (APM) upregulation, and immune cell infiltration in tissue at baseline and post-treatment.
    2. Changes in the characterization of local tissue effects, proportion and phenotype, of intratumoral leukocyte subsets post-treatment.
    3. Changes in T cell receptor clonal expansion and persistence of initial clones post- treatment.
    4. Changes in FOXP3 methylation and quantification of regulatory T cells post- treatment.

  • Immunologic effects of IL-12 plasmid electroporation in peripheral blood mononuclear cells (PBMCs). [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    1. Changes in the proportion of circulating regulatory and effector T cells in peripheral blood.
    2. Changes in phenotype of leukocyte subsets and T cell receptor clonal expansion

  • Quality of Life (QoL) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    QoL will be assessed through use of Skindex29, FACT-G (Functional Assessment of Cancer Therapy -General) and VAS-P (Visual Analog for Pruritus) questionnaires. Subjects will complete the self - reported measures prior to clinical evaluations every 4 week


Estimated Enrollment: 34
Study Start Date: July 2012
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
All subjects may receive up to six cycles of treatment consisting of two treatment days, Days 1 and 8, in a 28-day cycle. Patients will receive intratumoral injection of pIL-12 at a concentration of 0.5 mg/mL and a fixed volume of 0.25 mL per each 1.0 cm diameter of target region, followed immediately by electrical discharge around the tumor site resulting in electroporation of plasmid DNA into tumor cells. Up to a maximum of 8 fixed volume injections followed by electroporation may be administered on each day of treatment and the total number is dependent upon the size of each individual lesion, or affected areas in erythrodermic patients.
Drug: IL-12 plasmid (pIL-12)
All subjects may receive up to six cycles of treatment consisting of two treatment days, Days 1 and 8, in a 28-day cycle. Patients will receive intratumoral injection of IL-12 plasmid (pIL-12) at a concentration of 0.5 mg/mL and a fixed volume of 0.25 mL per each 1.0 cm diameter of target region. Up to a maximum of 8 fixed volume injections per patient per day depending up on the size of each individual lesion, or affected areas in erythrodermic patients.
Other Name: Interleukin-12
Device: Electroporation
Electroporation of the target lesion will occur using the OncoSec Medical System (OMS). Six pulses at field strengths of (E+) of 1500 V/cm and pulse width of 100 μs at 1-second intervals will be administered to each previously injected region. Up to 8 target regions may be treated on Days 1 and 8 of each cycle. A total of three cycles may be completed at 4-week intervals.
Other Name: Electropermeabilization

Detailed Description:

This is a single arm, open label, multi-center phase 2 study to assess the safety and anti-tumor activity of intratumoral pIL-12 electroporation in subjects with stage IB to IIIB mycosis fungoides. All subjects may receive up to six cycles of treatment consisting of two treatment days, Days 1 and 8, in a 28-day cycle. Patients will receive intratumoral injection of pIL-12 at a concentration of 0.5 mg/mL and a fixed volume of 0.25 mL per each 1.0 cm diameter of target region, followed immediately by electrical discharge around the tumor site resulting in electroporation of plasmid DNA into tumor cells. Up to a maximum of 8 fixed volume injections followed by electroporation may be administered on each day of treatment and the total number is dependent upon the size of each individual lesion, or affected areas in erythrodermic patients. Prior to the first cycle of treatment, the investigator will select at least one lesion, or affected area in erythrodermic patients, to be left untreated for the duration of the study to allow for clinical observation of an untreated site. Subjects will be followed for safety and clinical evaluation every 4 weeks. Quality of Life will be assessed using the Skindex29, Functional Assessment of Cancer Therapy - General (FACT-G) and Visual Analog Scale for Pruritus (VAS-P) instruments. Survival follow up will occur at 3-month intervals over 2 years following end of study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Biopsy confirmed mycosis fungoides of stage IB - IIIB;
  2. Subjects must have failed or have been intolerant to at least one standard of care therapy;
  3. Subjects 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. Subjects 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. Subjects must have 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;
    • 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 subjects 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;
    • Serum bilirubin within institutional normal limits;
    • AST and ALT < 1.5x 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 subject participation on study;
  4. Concurrent steroid therapy;
  5. Concurrent anticoagulant therapy (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), HTL V -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. 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 subject's participation in the study, or to interfere with the interpretation of the results;
  12. Subjects 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01579318

Locations
United States, California
UCSF Helen Diller Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Pennsylvania
The Hospital of University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
OncoSec Medical Incorporated
Investigators
Principal Investigator: Weiyun Ai, M.D. University of California, San Francisco
  More Information

No publications provided

Responsible Party: OncoSec Medical Incorporated
ClinicalTrials.gov Identifier: NCT01579318     History of Changes
Other Study ID Numbers: CC# 10861
Study First Received: April 15, 2012
Last Updated: June 15, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Mycosis Fungoides
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on July 27, 2015