Phase II Intratumoral IL12 Plasmid Electroporation in Cutaneous Lymphoma

NCT01579318 | Terminated Phase 2 Results DMC

• 1 other identifier: OMS-I120
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cutaneous T Cell Lymphomas (CTCL); Mycosis Fungoides (MF)

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate Assessed by Modified Severity Weighted Assessment Tool (mSWAT) Score in the Skin

  ORR is defined as the percentage of participants that achieved a complete response (CR) or partial response (PR) as assessed by mSWAT score. The mSWAT defines 3 lesion types and assigns each a weighing factor: patch (no induration or significant elevation)=1; plaque (induration, crusting, ulceration or poikiloderma)=2; tumor (solid or nodular ≥ 1 cm in diameter with evidence of deep infiltration and/or vertical growth)=4. Lesions are assessed by body surface area (BSA) where palm + fingers = approximately 1% BSA in each of 12 areas (head, neck, anterior trunk, arms, forearms, hands, posterior trunk, buttocks, thighs, legs, feet, groin), and the sum of each area of BSA is multiplied by its weighing factor. An overall sum of each subtotal represents the mSWAT score (0=no lesions; 400=lesions covering all areas). CR=100% clearance of skin lesions; PR= 50%-99% clearance of skin disease from baseline without new tumors ( ≥1.0 cm in diameter) in patients with T1, T2 or T4 only skin disease.

  Every 28 days for the first 24-weeks of treatment

• Objective Response Rate Assessed by Modified Severity Weighted Assessment Tool (mSWAT) Composite Global Score

  ORR is defined as the percentage of participants that achieved a complete response (CR) or partial response (PR) as assessed by mSWAT Composite Global Score. This assessment evaluated skin, lymph node, blood and visceral involvement. The response generated in each category was used to determine the Global ORR: CR=complete disappearance of all clinical evidence of disease or, no involvement of disease at baseline through time of response evaluation (NI); PR=regression of measurable disease as follows: 100% clearance of skin lesions, all other categories do not have CR/NI and no category has progressive disease (PD) -OR- 50%-99% clearance of skin disease from baseline without new tumors ( ≥1.0 cm in diameter) in patients with T1, T2 or T4 only skin disease, and if any other category was involved at baseline, at least one has CR/PR and no category has PD.

  Every 28 days for the first 24-weeks of treatment

Secondary Outcomes (4)

• Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  From the start of study treatment up to 340 days

• Duration of Overall Objective Response Assessed by mSWAT Skin Score

  From first documented response until disease progression (Up to 340 days)

• Time to Overall Objective Response Assessed by mSWAT Skin Score

  From start of study treatment until overall objective response (Up to 340 days)

• Quality of Life (QoL)

  Every 28 days for up to 340 days

Other Outcomes (2)

• Immunologic Effects of IL-12 Plasmid Electroporation in Tissue

  2 years

• Immunologic Effects of IL-12 Plasmid Electroporation in Peripheral Blood

  2 years

Study Arms (1)

Treatment

EXPERIMENTAL

Participants received up to 4 cycles of treatment (3 daily treatments on Days 1, 5 and 8, in a 12-week cycle) of intratumoral injection(s) 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.

Biological: Tavokinogene Telseplasmid (tavo); Device: OncoSec Medical System (OMS)

Interventions

Tavokinogene Telseplasmid (tavo) BIOLOGICAL

Patients received intratumoral injection(s) of tavo.

Also known as: interleukin-12 gene, IL-12 gene, pIL-12, plasmid DNA encoding human interleukin-12, plasmid IL-12

Treatment

OncoSec Medical System (OMS) DEVICE

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.

Also known as: MedPulser

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Biopsy confirmed mycosis fungoides of stage IB - IIIB;
• Participants must have failed or have been intolerant to at least one standard of care therapy;
• 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;
• Participants must have one additional lesion, or affected area in erythrodermic patients, that remains untreated for the duration of the study;
• Age ≥ 18 years old;
• Participants must have Eastern Cooperative Oncology Group (ECOG) performance status 0-2;
• 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;

You may not qualify if:

• Prior therapy with IL-12 or prior gene therapy;
• Prior treatment with Campath (alemtuzumab) within 1 year of enrollment;
• Concurrent immunotherapy, chemotherapy, or radiation therapy for duration of patient participation on study;
• Concurrent steroid therapy;
• Concurrent anticoagulant therapy (acetylsalicylic acid \[ASA\]≤ 325mg/day allowed);
• Evidence of significant active infection (e.g., pneumonia, cellulitis, wound abscess, etc.) at time of study enrollment;
• 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);
• 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);
• 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;
• 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);
• 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;
• Participants 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 as effects on the fetus are unknown and there may be a risk of increased fetal wastage.

Sponsors & Collaborators

• OncoSec Medical Incorporated: lead

Study Sites (1)

UCSF Helen Diller Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

MeSH Terms

Conditions

Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

Study enrollment was prematurely terminated under protocol version 6.0. No patients signed informed consent under version 7.0. Two (2) of the targeted 27 patients were enrolled. Thus, a formal statistical analysis was not performed.

Results Point of Contact

• Title: Sharron E Gargosky, Chief Clinical Regulatory Officer
• Organization: OncoSec Medical Incorporated

ClinicalTrialsInfo@OncoSec.com

+1 858-255-4729

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2012
• First Posted: April 17, 2012
• Study Start: June 8, 2012
• Primary Completion: June 3, 2014
• Study Completion: June 3, 2014
• Last Updated: May 15, 2023
• Results First Posted: January 3, 2018

Record last verified: 2023-05

Locations

US (1)