Limbal Stem Cell Deficiency (LSCD) Treatment With Cultivated Stem Cell (CALEC) Graft

NCT ID: NCT02592330

Last Updated: 2025-01-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-01
• Study Completion Date: 2023-03-31

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.

Conditions

Limbal Stem Cell Deficiency

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cultivated Autologous Limbal Epithelial Cell (CALEC) graft

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.

Group Type: EXPERIMENTAL

Biopsy to collect limbal epithelial stem cells that will be cultivated into a graft

Intervention Type: PROCEDURE

Cultivated autologous limbal epithelial cell (CALEC) therapy utilizes a bio-engineered composite of ex vivo expanded autologous corneal epithelial cells and an FDA-approved amniotic membrane (AmnioGraft®, Bio-Tissue, Inc.) to reconstruct the ocular surface. A small biopsy (2-3 mm2) from the patient's contralateral eye serves as a source epithelial (stem) cells that are expanded on the amniotic membrane in culture and the resulting product is surgically transplanted onto the cornea after excision of the fibrovascular pannus.

Cultivation of Limbal epithelial cells into a graft

Intervention Type: BIOLOGICAL

A graft is manufactured for transplant

CALEC Transplant

Intervention Type: PROCEDURE

Limbal epithelial cells are obtained from the healthy fellow eye and cultivated in a lab for later transplantation into the diseased eye.

Interventions

Biopsy to collect limbal epithelial stem cells that will be cultivated into a graft

Cultivated autologous limbal epithelial cell (CALEC) therapy utilizes a bio-engineered composite of ex vivo expanded autologous corneal epithelial cells and an FDA-approved amniotic membrane (AmnioGraft®, Bio-Tissue, Inc.) to reconstruct the ocular surface. A small biopsy (2-3 mm2) from the patient's contralateral eye serves as a source epithelial (stem) cells that are expanded on the amniotic membrane in culture and the resulting product is surgically transplanted onto the cornea after excision of the fibrovascular pannus.

Intervention Type: PROCEDURE

Cultivation of Limbal epithelial cells into a graft

A graft is manufactured for transplant

Intervention Type: BIOLOGICAL

CALEC Transplant

Limbal epithelial cells are obtained from the healthy fellow eye and cultivated in a lab for later transplantation into the diseased eye.

Intervention Type: PROCEDURE

Other Intervention Names

Cultivated Autologous Limbal Epithelial Cell (CALEC); Conjunctival Limbal Autograft

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 89 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts Eye and Ear Infirmary

OTHER

Sponsor Role: lead

Dana-Farber Cancer Institute

OTHER

Sponsor Role: collaborator

Responsible Party

Ula Jurkunas

Associate Professor, Harvard Medical School

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ula Jurkunas, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts Eye and Ear Infirmary

Locations

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, United States

Countries

United States

References

Yavuz Saricay L, Kaufman AR, Johns LK, Yin J, Samarakoon L, Ayala AR, Maguire M, Parekh M, Hernandez Rodriguez DE, Daley H, Dana R, Armant M, Ritz J, Jurkunas UV. Central Cornea Changes on Anterior Segment OCT and In Vivo Confocal Microscopy After Autologous Limbal Epithelial Cell Transplantation. Cornea. 2025 Mar 28. doi: 10.1097/ICO.0000000000003865. Online ahead of print.

Reference Type: DERIVED

PMID: 40152603 (View on PubMed)

Jurkunas UV, Kaufman AR, Yin J, Ayala A, Maguire M, Samarakoon L, Johns LK, Parekh M, Li S, Gauthier A, Negre H, Shaw KL, Hernandez Rodriguez DE, Daley H, Dana R, Armant M, Ritz J. Cultivated autologous limbal epithelial cell (CALEC) transplantation for limbal tem cell deficiency: a phase I/II clinical trial of the first xenobiotic-free, serum-free, antibiotic-free manufacturing protocol developed in the US. Nat Commun. 2025 Mar 4;16(1):1607. doi: 10.1038/s41467-025-56461-1.

Reference Type: DERIVED

PMID: 40038272 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

14-124H

Identifier Type: -

Identifier Source: org_study_id