Clinical trial NCT02592330: Limbal Stem Cell Deficiency (LSCD) Treatment With Cultivated Stem Cell (CALEC) Graft
Official title: Safety and Feasibility of Cultivated Autologous Limbal Epithelial Cell Transplantation in the Treatment of Limbal Stem Cell Deficiency (LSCD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Limbal Stem Cell Deficiency
Keywords: LSCD treatment
Limbal Stem Cell Deficiency
CALEC
Cultivated Autologous Limbal Epithelial Cell Transplantation
Corneal epithelial stem cells
Corneal scarring
Corneal opacity
Chemical injury eye
Thermal injury eye
Autologous stem cell
Epithelial defect
Corneal cloudiness
Ocular burn
Ocular injury
Autograft
Conjunctival Limbal Autograft
LSCD research
Chronic contact lens wear
Chronic keratoconjunctivitis
Corneal conjunctivalization
Corneal fibrovascular pannus
Corneal neovascularization
Corneal regeneration
Infectious keratitis
Limbal epithelial stem cell deficiency
Ocular injury drug toxicity
Ocular surface disorder
Neovascularization pannus
Neurotrophic keratitis
Ocular surface Inflammation
Eye injury ionizing radiation
Eye injury ultraviolet radiation
Corneal pannus
Corneal wound healing
Neurotrophic keratopathy
LSCD trial
Stem cell therapy
Epithelial surface integrity
Regrowing corneas
Lead sponsor: Massachusetts Eye and Ear Infirmary
Sponsor class: OTHER
Collaborators: name: Dana-Farber Cancer Institute
First posted: 2015-10-30
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All subjects will receive the study intervention, a stem cell graft cultivated from their own cells.
Primary purpose: TREATMENT

Brief summary: The main aim of the study is to determine the safety and feasibility of a cultivated autologous limbal epithelial cell (CALEC) transplantation in the treatment of limbal stem cell deficiency.

Detailed description: This is an open label, single center study to assess safety, feasibility, and efficacy of Cultivated Autologous Limbal Epithelial Cell (CALEC) grafts in 17 patients with unilateral limbal stem cell deficiency (LSCD).

Participants will have a corneal biopsy in their non-diseased eye, which will provide cells for the creation of the CALEC graft. The CALEC will be made at the Good Manufacturing Practice (GMP) Laboratory, Dana Farber Cancer Institute and transported to Mass. Eye and Ear Infirmary for application to the participant's diseased eye during their standard corneal reconstruction procedure. Subjects will be monitored up to month 18 post-transplant to assess for any delayed adverse events of the product (CALEC) or procedure as well as assessment of the durability of the transplant.

Eligibility criteria: Inclusion Criteria:

* Male or female participants age 18 to \<90 years old at time of enrollment
* Ability of a subject or guardian/legal representative to provide written informed consent and to comply with study assessments for the full duration of the study.
* Patients with unilateral limbal stem cell deficiency (LSCD) as determined by conjunctivalization of the cornea defined by fibrovascular pannus more than 2 mm from the limbus for greater than or equal to 6 clock hours.
* Additional optional criteria:

  * Lack of limbal palisades of Vogt for greater than or equal to 9 clock hours
  * Goblet cell presence as defined by impression cytologic criteria

Exclusion Criteria:

* Corneal or ocular surface infection within 30 days prior to study entry or CALEC transplantation
* Ocular surface malignancy
* Uncontrolled diabetes with most recent HgA1c greater than 8.5%
* Renal Failure with eGFR below 60 mL/min per 1.73 m2
* Aspartate aminotransferase and alanine aminotransferase levels greater than 3 times institutional upper limit of normal
* Total bilirubin greater than 2 times institutional upper limit of normal (except patients with known Gilbert's syndrome)
* Platelet levels less than 100,000 or greater than 450,000 per microliter
* Hemoglobin levels of less than 11.0 g/dL in men or less than 10.0 g/dL in women
* Prothrombin time greater than 16 seconds and activated partial thromboplastin time greater than 35 seconds in patients not taking warfarin and an international normalized ratio greater than 3 in patients taking warfarin
* Inability to tolerate monitored anesthesia
* HIV infection or AIDS
* Active Hepatitis B or C
* Pregnancy (positive test) or lactation
* Participation in another simultaneous medical investigation or trial
* Severe cicatricial eye disease
* Severe dry eye disease as determined by Schirmer's test less than 1mm in at least one eye.
* Any medical, psychiatric, debilitating disease/disorder or social condition that in the judgment of the investigator would interfere with or serve as a contraindication to adherence to the study protocol or ability to give informed consent.
* Signs of current infection, including fever and current treatment with antibiotics.
* History of allo-limbal transplantation
* Presence of allergy to the CALEC graft or any of the chemical components within its formulation.

Exclusion Based on Donor Eye:

* Conjunctivalization of the cornea defined by fibrovascular pannus more than 2 mm from the limbus for greater than or equal to 3 clock hours
* Lack of limbal palisades of Vogt for greater than or equal to 3 clock hours
* History of allo-limbal transplantation

Primary outcomes:
measure: Primary Safety Events of Interest
timeFrame: 18 Months
measure: Manufacturing Feasibility Measures
timeFrame: 18 Months
Secondary outcomes:
measure: Measure of Transplant Efficacy
timeFrame: 18 Months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts Eye and Ear Infirmary
state: Massachusetts
Study officials:
affiliation: Massachusetts Eye and Ear Infirmary
name: Ula Jurkunas, MD
role: PRINCIPAL_INVESTIGATOR
References: