Clinical Trials /

Micro Needle Array-Doxorubicin (MNA-D) in Patients With Cutaneous T-cell Lymphoma (CTCL)

NCT02192021

Description:

The study hypothesis is that in situ MNA-directed chemo-immunotherapy using doxorubicin will kill tumor cells locally and alter the tumor microenvironment to induce durable systemic tumor-specific immunity. The purpose of this study is to test a new method of experimental treatment for CTCL, using small adhesive-like patches (a micro-needle applicator or MNA for short), which have dozens of very small micro-needles loaded with extremely low doses of doxorubicin, a chemotherapy agent. The overall goal of this study is to test the safety and effectiveness of these patches. We also want to determine which micro-dose of the drug is the best to achieve the best response. To make sure that we observe the effects of the very low dose of the drug and not the MNA patch itself, we will also use a placebo (a patch without drug in some patients) in addition to the doxorubicin coated patches. We will thoroughly evaluate the skin where the patches are applied. Once the best dose is determined for use in the patch, we will also begin to look at how well the patches work in clearing the skin.

Related Conditions:
  • Primary Cutaneous T Cell Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Micro Needle Array-Doxorubicin (MNA-D) in Patients With Cutaneous T-cell Lymphoma (CTCL)
  • Official Title: Phase I, Single-Arm, Open-Label, Dose Escalation Trial of MNA-Doxorubicin (MNA-D) in Patients-Subjects With Cutaneous T-cell Lymphoma (CTCL)

Clinical Trial IDs

  • ORG STUDY ID: PRO14030589
  • NCT ID: NCT02192021

Conditions

  • Cutaneous T Cell Lymphoma

Interventions

DrugSynonymsArms
Micro needle array-Doxorubicin (MNA-D)patch, doxorubicinMicro needle array-Doxorubicin (MNA-D)

Purpose

The study hypothesis is that in situ MNA-directed chemo-immunotherapy using doxorubicin will kill tumor cells locally and alter the tumor microenvironment to induce durable systemic tumor-specific immunity. The purpose of this study is to test a new method of experimental treatment for CTCL, using small adhesive-like patches (a micro-needle applicator or MNA for short), which have dozens of very small micro-needles loaded with extremely low doses of doxorubicin, a chemotherapy agent. The overall goal of this study is to test the safety and effectiveness of these patches. We also want to determine which micro-dose of the drug is the best to achieve the best response. To make sure that we observe the effects of the very low dose of the drug and not the MNA patch itself, we will also use a placebo (a patch without drug in some patients) in addition to the doxorubicin coated patches. We will thoroughly evaluate the skin where the patches are applied. Once the best dose is determined for use in the patch, we will also begin to look at how well the patches work in clearing the skin.

Detailed Description

      This study will evaluate a novel approach to the treatment of patches and plaques in the
      skin of patients diagnosed with cutaneous t-cell lymphoma utilizing a dissolvable
      microneedle array (MNA) delivery device that is used to directly and specifically deliver a
      drug to the tumor microenvironment for skin cancer therapy. We will utilize MNAs to deliver
      a well-characterized, potent chemotherapeutic agent (doxorubicin) to kill topically
      accessible, cutaneous T-cell lymphoma cells. In addition to directly killing cancer cells,
      doxorubicin is known to induce an immunologic cell death with the potential to
      simultaneously convert a cutaneous neoplasm into a highly potent patient specific immunogen
      capable of inducing innate, adaptive, and tumor specific effector and memory immune
      responses. Importantly, doxorubicin is currently in clinical use with a well-established
      safety profile. It is anticipated that use of the MNA-Doxorubicin (MNA-D) delivery system
      will enable direct and specific delivery of chemotherapy to the tumor, thereby avoiding any
      potential for systemic toxicity. The study will be conducted in two phases, with the first
      being a safety dose-finding phase and the second phase for efficacy and safety evaluation.
    

Trial Arms

NameTypeDescriptionInterventions
Micro needle array-Doxorubicin (MNA-D)ExperimentalMNA-D application for all subjects
  • Micro needle array-Doxorubicin (MNA-D)

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of Cutaneous T-cell Lymphoma (CTCL) based upon a skin biopsy diagnostic of
             atypical epidermotropism of folliculocentric or epidermotropic T-cells.

          -  Current stage of IA or IB.

          -  Expected survival of greater than or equal to12 months.

          -  Not be on any other investigational device/drug treatment.

          -  Have a sufficient number (i.e., n=4 for first dose cohort in Initial Safety
             Evaluation; n=3 for remainder of subjects) and surface area (> 5 cm2) of CTCL patches
             or plaques for Micro needle array-Doxorubicin (MNA-D) and Micro needle array (MNA)
             application.

          -  Willing to adhere to the instructions of the Investigator and his research team and
             sign an Informed Consent Form prior to entry into the study.

          -  Have the following initial and subsequent pretreatment laboratory parameters:
             granulocytes ≥2,000/mm3; platelets >50,000/mm3; serum creatinine ≤2X the upper limit
             of normal (ULN); AST, ALT, , LDH, Alk phos ≤3X the ULN.Subjects must be ³ 18 years of
             age and must be able to understand the written informed consent/assent document.

          -  Have no evidence of active infection, regardless of the degree of severity or
             localization. Subjects with active infections (whether or not they require antibiotic
             therapy) may be eligible for study participation after complete resolution of the
             infection. Subjects on antibiotic therapy must be off antibiotics before beginning
             treatment.

          -  Not receive any other treatment for CTCL except emollients of subject's choice
             without topical steroids, anti-fungal or antibacterial topical preparations.

          -  Willing to discontinue concomitant medications for CTCL for the duration of their
             study participation, including: high dose topical steroids - 2 week washout; oral
             steroids above 10 mg - 3 week washout; Psoralen + Ultraviolet A light (PUVA) or
             ultraviolet B light (UVB) (including sunbathing, tanning beds, etc.) - 2 week
             washout; extracorporeal photopheresis - 2 week washout; Electron Beam - 2 weeks
             washout; chemotherapeutic agents - 3 week washout; bexarotene capsules or other oral
             biologics - 2 week washout; and topical nitrogen mustard - 2 week washout.

          -  May re-enroll in the study if greater than 4 weeks elapses between courses and if all
             other inclusion/exclusion criteria are met.

        Exclusion Criteria:

          -  Uncontrolled pain.

          -  Known history of autoimmune disease; or active HIV, HTLV-1, and/or hepatitis
             infection.

          -  Pregnant or lactating.

          -  Have sensitivity to drugs that provide local anesthesia.

          -  Have active malignancies with the exception of non-metastatic prostate cancer and
             carcinoma in situ of the skin and cervix.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Evaluate the safety of the micro array needle doxorubicin (MNA-D) system confirmed by vital signs, hematology, comprehensive metabolic panel, assessment for skin toxicity, and adverse event evaluation.
Time Frame:9 weeks
Safety Issue:
Description:A traditional 3 + 3 dose escalation design will be used in 4 dosage cohorts (25 ug, 50 ug, 100 ug, and 200 ug).

Secondary Outcome Measures

Measure:Evaluate the clinical responses (i.e., effectiveness) by the MNA-D
Time Frame:12 months
Safety Issue:
Description:We will evaluate local, locoregional, and distant tumor regression; characterize and compare treated skin and the tumor microenvironment before, during, and after therapy

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Pittsburgh

Trial Keywords

  • CTCL
  • Cutaneous T-cell Lymphoma
  • Mycosis Fungoides

Last Updated

March 23, 2017