<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02192021</url>
  </required_header>
  <id_info>
    <org_study_id>PRO14030589</org_study_id>
    <nct_id>NCT02192021</nct_id>
  </id_info>
  <brief_title>Micro Needle Array-Doxorubicin (MNA-D) in Patients With Cutaneous T-cell Lymphoma (CTCL)</brief_title>
  <acronym>MNA-D</acronym>
  <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)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Falo, Louis, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study hypothesis is that in situ MNA-directed chemo-immunotherapy using doxorubicin will&#xD;
      kill tumor cells locally and alter the tumor microenvironment to induce durable systemic&#xD;
      tumor-specific immunity.&#xD;
&#xD;
      The purpose of this study is to test a new method of experimental treatment for CTCL, using&#xD;
      small adhesive-like patches (a micro-needle applicator or MNA for short), which have dozens&#xD;
      of very small micro-needles loaded with extremely low doses of doxorubicin, a chemotherapy&#xD;
      agent. The overall goal of this study is to test the safety and effectiveness of these&#xD;
      patches. We also want to determine which micro-dose of the drug is the best to achieve the&#xD;
      best response. To make sure that we observe the effects of the very low dose of the drug and&#xD;
      not the MNA patch itself, we will also use a placebo (a patch without drug in some patients)&#xD;
      in addition to the doxorubicin coated patches. We will thoroughly evaluate the skin where the&#xD;
      patches are applied. Once the best dose is determined for use in the patch, we will also&#xD;
      begin to look at how well the patches work in clearing the skin.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will evaluate a novel approach to the treatment of patches and plaques in the skin&#xD;
      of patients diagnosed with cutaneous t-cell lymphoma utilizing a dissolvable microneedle&#xD;
      array (MNA) delivery device that is used to directly and specifically deliver a drug to the&#xD;
      tumor microenvironment for skin cancer therapy. We will utilize MNAs to deliver a&#xD;
      well-characterized, potent chemotherapeutic agent (doxorubicin) to kill topically accessible,&#xD;
      cutaneous T-cell lymphoma cells. In addition to directly killing cancer cells, doxorubicin is&#xD;
      known to induce an immunologic cell death with the potential to simultaneously convert a&#xD;
      cutaneous neoplasm into a highly potent patient specific immunogen capable of inducing&#xD;
      innate, adaptive, and tumor specific effector and memory immune responses. Importantly,&#xD;
      doxorubicin is currently in clinical use with a well-established safety profile. It is&#xD;
      anticipated that use of the MNA-Doxorubicin (MNA-D) delivery system will enable direct and&#xD;
      specific delivery of chemotherapy to the tumor, thereby avoiding any potential for systemic&#xD;
      toxicity. The study will be conducted in two phases, with the first being a safety&#xD;
      dose-finding phase and the second phase for efficacy and safety evaluation. The first phase&#xD;
      is now completed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 9, 2016</start_date>
  <completion_date type="Anticipated">June 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2024</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <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.</measure>
    <time_frame>9 weeks</time_frame>
    <description>A traditional 3 + 3 dose escalation design will be used in 4 dosage cohorts (25 ug, 50 ug, 100 ug, and 200 ug).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluate the clinical responses (i.e., effectiveness) by the MNA-D</measure>
    <time_frame>12 months</time_frame>
    <description>We will evaluate local, locoregional, and distant tumor regression; characterize and compare treated skin and the tumor microenvironment before, during, and after therapy</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Evaluate the tumor immunity induced by the MNA-D</measure>
    <time_frame>12 months</time_frame>
    <description>Generalized skin changes, tissue and blood will be analyzed for immunologic response to the MNA-D in treated and control control cutaneous T-cell lymphoma lesions</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Cutaneous T Cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>Micro needle array-Doxorubicin (MNA-D)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MNA-D application for all subjects</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Micro needle array-Doxorubicin (MNA-D)</intervention_name>
    <description>MNA-D patches will be applied to 3-4 CTCL skin patches or plaques at each weekly visit (4/cycle). The initial safety, dose-finding phase will include one cycle of applications and the second phase will include weekly applications (4/cycle) for up to 6-8 cycles.</description>
    <arm_group_label>Micro needle array-Doxorubicin (MNA-D)</arm_group_label>
    <other_name>patch</other_name>
    <other_name>doxorubicin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of Cutaneous T-cell Lymphoma (CTCL) based upon a skin biopsy diagnostic of&#xD;
             atypical epidermotropism of folliculocentric or epidermotropic T-cells.&#xD;
&#xD;
          -  Current stage of IA or IB.&#xD;
&#xD;
          -  Expected survival of greater than or equal to12 months.&#xD;
&#xD;
          -  Not be on any other investigational device/drug treatment.&#xD;
&#xD;
          -  Have a sufficient number (i.e., n=4 for first dose cohort in Initial Safety&#xD;
             Evaluation; n=3 for remainder of subjects) and surface area (&gt; 5 cm2) of CTCL patches&#xD;
             or plaques for Micro needle array-Doxorubicin (MNA-D) and Micro needle array (MNA)&#xD;
             application.&#xD;
&#xD;
          -  Willing to adhere to the instructions of the Investigator and his research team and&#xD;
             sign an Informed Consent Form prior to entry into the study.&#xD;
&#xD;
          -  Have the following initial and subsequent pretreatment laboratory parameters:&#xD;
             granulocytes ≥2,000/mm3; platelets &gt;50,000/mm3; serum creatinine ≤2X the upper limit&#xD;
             of normal (ULN); AST, ALT, , LDH, Alk phos ≤3X the ULN.Subjects must be ³ 18 years of&#xD;
             age and must be able to understand the written informed consent/assent document.&#xD;
&#xD;
          -  Have no evidence of active infection, regardless of the degree of severity or&#xD;
             localization. Subjects with active infections (whether or not they require antibiotic&#xD;
             therapy) may be eligible for study participation after complete resolution of the&#xD;
             infection. Subjects on antibiotic therapy must be off antibiotics before beginning&#xD;
             treatment.&#xD;
&#xD;
          -  Not receive any other treatment for CTCL except emollients of subject's choice without&#xD;
             topical steroids, anti-fungal or antibacterial topical preparations.&#xD;
&#xD;
          -  Willing to discontinue concomitant medications for CTCL for the duration of their&#xD;
             study participation, including: high dose topical steroids - 2 week washout; oral&#xD;
             steroids above 10 mg - 3 week washout; Psoralen + Ultraviolet A light (PUVA) or&#xD;
             ultraviolet B light (UVB) (including sunbathing, tanning beds, etc.) - 2 week washout;&#xD;
             extracorporeal photopheresis - 2 week washout; Electron Beam - 2 weeks washout;&#xD;
             chemotherapeutic agents - 3 week washout; bexarotene capsules or other oral biologics&#xD;
             - 2 week washout; and topical nitrogen mustard - 2 week washout.&#xD;
&#xD;
          -  May re-enroll in the study if greater than 4 weeks elapses between courses and if all&#xD;
             other inclusion/exclusion criteria are met.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Uncontrolled pain.&#xD;
&#xD;
          -  Known history of autoimmune disease; or active HIV, HTLV-1, and/or hepatitis&#xD;
             infection.&#xD;
&#xD;
          -  Pregnant or lactating.&#xD;
&#xD;
          -  Have sensitivity to drugs that provide local anesthesia.&#xD;
&#xD;
          -  Have active malignancies with the exception of non-metastatic prostate cancer and&#xD;
             carcinoma in situ of the skin and cervix.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Oleg E Akilov, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Jasmine C Hicks</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Bediz B, Korkmaz E, Khilwani R, Donahue C, Erdos G, Falo LD Jr, Ozdoganlar OB. Dissolvable microneedle arrays for intradermal delivery of biologics: fabrication and application. Pharm Res. 2014 Jan;31(1):117-35. doi: 10.1007/s11095-013-1137-x. Epub 2013 Aug 1.</citation>
    <PMID>23904139</PMID>
  </reference>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>July 10, 2014</study_first_submitted>
  <study_first_submitted_qc>July 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 16, 2014</study_first_posted>
  <last_update_submitted>May 1, 2023</last_update_submitted>
  <last_update_submitted_qc>May 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Oleg E. Akilov, MD, PhD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>CTCL</keyword>
  <keyword>Cutaneous T-cell Lymphoma</keyword>
  <keyword>Mycosis Fungoides</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, T-Cell</mesh_term>
    <mesh_term>Lymphoma, T-Cell, Peripheral</mesh_term>
    <mesh_term>Lymphoma, T-Cell, Cutaneous</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Liposomal doxorubicin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02192021
org study id: PRO14030589
nct id: NCT02192021
lead sponsor: 
has dmc: Yes
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.
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. The first phase
      is now completed.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
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
description: A traditional 3 + 3 dose escalation design will be used in 4 dosage cohorts (25 ug, 50 ug, 100 ug, and 200 ug).
measure: Evaluate the clinical responses (i.e., effectiveness) by the MNA-D
time frame: 12 months
description: We will evaluate local, locoregional, and distant tumor regression; characterize and compare treated skin and the tumor microenvironment before, during, and after therapy
measure: Evaluate the tumor immunity induced by the MNA-D
time frame: 12 months
description: Generalized skin changes, tissue and blood will be analyzed for immunologic response to the MNA-D in treated and control control cutaneous T-cell lymphoma lesions
arm group label: Micro needle array-Doxorubicin (MNA-D)
arm group type: Experimental
description: MNA-D application for all subjects
intervention type: Drug
intervention name: Micro needle array-Doxorubicin (MNA-D)
description: MNA-D patches will be applied to 3-4 CTCL skin patches or plaques at each weekly visit (4/cycle). The initial safety, dose-finding phase will include one cycle of applications and the second phase will include weekly applications (4/cycle) for up to 6-8 cycles.
arm group label: Micro needle array-Doxorubicin (MNA-D)
other name: patch
other name: doxorubicin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Oleg E Akilov, MD, PhD
role: Principal Investigator
affiliation: University of Pittsburgh
facility: 
country: United States
citation: Bediz B, Korkmaz E, Khilwani R, Donahue C, Erdos G, Falo LD Jr, Ozdoganlar OB. Dissolvable microneedle arrays for intradermal delivery of biologics: fabrication and application. Pharm Res. 2014 Jan;31(1):117-35. doi: 10.1007/s11095-013-1137-x. Epub 2013 Aug 1.
PMID: 23904139
responsible party type: Principal Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Oleg E. Akilov, MD, PhD
investigator title: Principal Investigator
mesh term: Lymphoma
mesh term: Lymphoma, T-Cell
mesh term: Lymphoma, T-Cell, Peripheral
mesh term: Lymphoma, T-Cell, Cutaneous
mesh term: Doxorubicin
mesh term: Liposomal doxorubicin
sharing ipd: No