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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02192021
Recruitment Status : Recruiting
First Posted : July 16, 2014
Last Update Posted : December 16, 2019
Information provided by (Responsible Party):
Oleg E. Akilov, MD, PhD, University of Pittsburgh

Tracking Information
First Submitted Date  ICMJE July 10, 2014
First Posted Date  ICMJE July 16, 2014
Last Update Posted Date December 16, 2019
Study Start Date  ICMJE January 2016
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 14, 2014)
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 ]
A traditional 3 + 3 dose escalation design will be used in 4 dosage cohorts (25 ug, 50 ug, 100 ug, and 200 ug).
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02192021 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 14, 2014)
Evaluate the clinical responses (i.e., effectiveness) by the MNA-D [ Time Frame: 12 months ]
We will evaluate local, locoregional, and distant tumor regression; characterize and compare treated skin and the tumor microenvironment before, during, and after therapy
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: July 14, 2014)
Evaluate the tumor immunity induced by the MNA-D [ Time Frame: 12 months ]
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
Original Other Pre-specified Outcome Measures Same as current
Descriptive Information
Brief Title  ICMJE Micro Needle Array-Doxorubicin (MNA-D) in Patients With Cutaneous T-cell Lymphoma (CTCL)
Official Title  ICMJE Phase I, Single-Arm, Open-Label, Dose Escalation Trial of MNA-Doxorubicin (MNA-D) in Patients-Subjects With Cutaneous T-cell Lymphoma (CTCL)
Brief Summary

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. The first phase is now completed.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cutaneous T Cell Lymphoma
Intervention  ICMJE Drug: Micro needle array-Doxorubicin (MNA-D)
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.
Other Names:
  • patch
  • doxorubicin
Study Arms  ICMJE Experimental: Micro needle array-Doxorubicin (MNA-D)
MNA-D application for all subjects
Intervention: Drug: Micro needle array-Doxorubicin (MNA-D)
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 14, 2014)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sue A McCann, MSN, RN 412-864-3681
Contact: Oleg Akilov, MD, PhD 412-864-3681
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02192021
Other Study ID Numbers  ICMJE PRO14030589
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Oleg E. Akilov, MD, PhD, University of Pittsburgh
Study Sponsor  ICMJE Falo, Louis, MD
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Oleg E Akilov, MD, PhD University of Pittsburgh
PRS Account University of Pittsburgh
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP