A Multicenter Phase II Trial of Intratumoral pIL-12 Electroporation in Cutaneous Lymphoma
18 Years
N/A
Both
Cutaneous T Cell Lymphomas (CTCL), Mycosis Fungoides (MF)
Trial Information
A Multicenter Phase II Trial of Intratumoral pIL-12 Electroporation in Cutaneous Lymphoma
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.
Inclusion Criteria:
- Biopsy confirmed mycosis fungoides of stage IB-IVA.
- Patients must have failed or have been intolerant of at least 2 topical or one
systemic treatment.
- Patients must have a minimum of 4 lesions, 2 for electroporation, and 2 for
evaluation of response.
- Age > 18 years old
- Patients must have ECOG performance status 0-2
- Patients must have creatinine < 2 x upper limit of normal, and serum bilirubin within
institutional normal limits obtained within 4 weeks prior to first dosing.
- Patients must have absolute neutrophil count (ANC) > 1000/mm and platelet count >
75,000 /mm within 4 weeks prior to first dosing.
- Required wash out periods for prior therapy:
- Topical therapy: 2 weeks from first dosing
- Chemotherapy: 4 weeks from first dosing
- Radiotherapy (including photo therapy): 4 weeks from first dosing
- Systemic biological therapy for mycosis fungoides: 4 weeks from first dosing
- Other investigational therapy: 4 weeks from first dosing
- Patients of reproductive potential and their partners must agree to use an effective
(>90% reliability) form of contraception during the study and for 4 weeks following
the last study drug administration.
- Women of reproductive potential must have negative urine pregnancy test.
- Life expectancy greater than 4 months from first dosing.
- Patients must be able to give informed consent and able to follow guidelines given in
the study
Exclusion Criteria:
- Patients with active infection or with a fever >38.50 C within three days prior to
the first scheduled treatment
- CNS metastases
- Known history of human immunodeficiency virus (HIV), hepatitis B or hepatitis C
(active, prior treatment, or both).
- Prior malignancy (active within 5 years of screening) except basal cell or completely
excised non-invasive squamous cell carcinoma of the skin, or in situ squamous cell
carcinoma of the cervix
- Current anticoagulant therapy (ASA<= 325mg/day allowed).
- Significant cardiovascular disease (i.e. NYHA class 3 congestive heart failure;
myocardial infarction with the past 6 months; unstable angina; coronary angioplasty
with the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias).
- Pregnant or lactating.
- Any other medical history, including laboratory results, deemed by the investigator
to be likely to interfere with their participation in the study, or to interfere with
the interpretation of the results.
- Patients with electronic pacemakers or defibrillators are excluded from this study as
the effect of electroporation on these devices is unknown.
- Pregnant and breast feeding women are excluded from the study because effects on the
fetus are unknown and there may be a risk of increased fetal wastage.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Local and distant response rate in patients treated with pIL-12
Outcome Description:
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.
Outcome Time Frame:
28 days from day 1 of treatment
Safety Issue:
No
Principal Investigator
Weiyun Ai, M.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of California, San Francisco
Authority:
United States: Food and Drug Administration
Study ID:
CC# 10861
NCT ID:
NCT01579318
Start Date:
July 2012
Completion Date:
June 2015
Related Keywords:
- Cutaneous T Cell Lymphomas (CTCL)
- Mycosis Fungoides (MF)
- Lymphoma
- Mycoses
- Mycosis Fungoides
- Lymphoma, T-Cell
- Lymphoma, T-Cell, Cutaneous
Name | Location |
|---|---|
| UCSF Helen Diller Comprehensive Cancer Center | San Francisco, California 94143 |
