Evaluation of Safety & Efficacy for the Prevention of Ocular GVHD With Ophthalmic Tacrolimus vs Cyclosporine in Allo-HSCT

NCT06348602 | Recruiting Phase 1 DMC

• 1 other identifier: PI23-00201
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic GVHD (cGVHD) is a predominant cause of mortality and disability not related to relapse; it occurs in 30 to 70% of patients. The majority of patients with cGVHD present with ocular involvement with a reported incidence of 40-60%. Symptoms can range from mild dry eye syndrome to severe epithelial defects that can generate corneal perforation and loss of vision. The most accepted pharmacological modality is the topical application of cyclosporine A; on the other hand, tacrolimus has shown greater immunosuppressive power when used in ocular GVHD. However, this effectiveness is limited since by the time the manifestations appear, there is already permanent damage to the lacrimal gland due to the lymphocytic infiltration; so it is necessary to use a prevention strategy before these manifestations appear. Previously, the employment of ocular cyclosporine drops as ocular GVHD prophylaxis was assessed to evaluate safety and effectiveness, showing that it is well tolerated and can limit the appearance of severe dry eye manifestations in a small group of patients. The purpose of this work is to compare the two modalities currently accepted for the treatment of the disease, but in a prophylactic way; topical ciclosporin A against topical tacrolimus, to determine the safety and efficiency of each of them as a preventive measure to limit the risk of developing the appearance of ocular cGVHD and the permanent consequences that this generates.

Conditions

Ocular Graft-versus-host Disease

Keywords

Allogeneic; Hematopoietic Stem Cell Transplantation; Dry eye syndrome

Outcome Measures

Primary Outcomes (1)

• Incidence of ocular graft-versus-host disease in patients undergoing allo-HSCT receiving topical prophylaxis with Cyclosporine A or Tacrolimus as assessed by the International Consensus Criteria on chronic ocular graft-versus-host disease.

  Severity based on an aggregate of scores of the following parameters: Schirmer's test \[mm\] (0, \>15; 1, 11-15; 2, 6-10; 3, ≤5), Corneal fluorescein staining \[points\] (0, 0; 1, \<2; 2, 2-3; 3, ≥4), Ocular Surface Disease Index \[points\] (0, \<13; 1, 13-22; 2, 23-32; 3, ≥33), Conjunctival injection \[points\] (0, None; 1, Mild/Moderate; 2, Severe). Graded as none (0-4 points), mild/moderate (5-8 points) and severe (9-11 points), where higher scores mean a worse outcome.

  2.5 years

Secondary Outcomes (12)

• Incidence of ocular graft-versus-host disease in patients undergoing allo-HSCT receiving topical prophylaxis with Cyclosporine A or Tacrolimus as assessed by the National Institutes of Health Consensus Development Projects on Chronic GVHD scoring system.

  2.5 years

• Prevalence of ocular GVHD based on historical records in the hematology service of the University Hospital U.A.N.L. in patients without prophylactic treatment as assessed by the International Consensus Criteria on chronic ocular graft-versus-host disease

  10 years

• Severity of ocular GVHD based on historical records in the hematology service of the University Hospital U.A.N.L. in patients without prophylactic treatment, as assessed by the International Consensus Criteria on chronic ocular graft-versus-host disease.

  10 years

• Prevalence of ocular GVHD based on historical records in the hematology service of the University Hospital U.A.N.L. in patients without prophylactic treatment, as assessed by the National Institutes of Health Consensus on Chronic GVHD scoring system.

  10 years

• Severity of ocular GVHD based on historical records in the hematology service of the University Hospital U.A.N.L. in patients without prophylactic treatment, as assessed by the National Institutes of Health Consensus on Chronic GVHD scoring system.

  10 years

Other Outcomes (1)

• Incidence of ocular GVHD in patients receiving prophylactic treatment for ocular GVHD.

  2.5 years

Study Arms (2)

Topical cyclosporine

ACTIVE COMPARATOR

Topical cyclosporine ophthalmic solution 0.1%, with a dosage of 1 drop in each eye every 12 hours, continued for a duration of 12 continuous months. Composition: Each ml contains Cyclosporine A 0.1% w/v (1 mg/ml) in a sterile aqueous vehicle q.s.

Drug: Cyclosporine ophthalmic solution 0.1%

Topical tacrolimus

EXPERIMENTAL

Topical tacrolimus ophthalmic ointment 0.03%, with a dosage of approximately 1 cm or the necessary amount to cover the lower fornix, every 12 hours, continued for a duration of 12 continuous months Composition: Each gram contains Tacrolimus 0.03% w/w (0.3 mg/g) in a sterile ointment base q.s.

Drug: Tacrolimus ophthalmic ointment 0.03%

Interventions

Cyclosporine ophthalmic solution 0.1% DRUG

Ophthalmic prophylaxis begins once engraftment is documented, with a dose of 1 drop in each eye every 12 hours, continued for a duration of 12 continuous months

Topical cyclosporine

Tacrolimus ophthalmic ointment 0.03% DRUG

Ophthalmic prophylaxis begins once engraftment is documented, with a dose of approximately 1 cm or the necessary amount to cover the lower fornix, every 12 hours, continued for a duration of 12 continuous months

Topical tacrolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients undergoing allogeneic HSCT.
• Patients 18 years of age or older.
• Patients who agree to participate in the study and sign the informed consent document.

You may not qualify if:

• Patients undergoing HSCT who do not continue their evaluation and follow-up in the Hematology Service of the University Hospital.
• Patients under 18 years of age.
• Patients who do not agree to participate in the study.
• Patients diagnosed with previous rheumatic disease.
• Patients with dermatological conditions undergoing systemic treatment.
• Patients with uncontrolled thyroid disease.

Sponsors & Collaborators

• Hospital Universitario Dr. Jose E. Gonzalez: lead

Study Sites (1)

Hospital Universitario de la U.A.N.L.

Nuevo León, Monterrey, 66640, Mexico

RECRUITING

Related Publications (3)

• Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, Palmer J, Weisdorf D, Treister NS, Cheng GS, Kerr H, Stratton P, Duarte RF, McDonald GB, Inamoto Y, Vigorito A, Arai S, Datiles MB, Jacobsohn D, Heller T, Kitko CL, Mitchell SA, Martin PJ, Shulman H, Wu RS, Cutler CS, Vogelsang GB, Lee SJ, Pavletic SZ, Flowers ME. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015 Mar;21(3):389-401.e1. doi: 10.1016/j.bbmt.2014.12.001. Epub 2014 Dec 18.

  PMID: 25529383 BACKGROUND

• Cantu-Rodriguez OG, Vazquez-Mellado A, Gonzalez-Trevino JL, Martinez-Garza DM, Gomez-De Leon A, Hawing-Zarate JA, Jaime-Perez JC, Gutierrez-Aguirre CH, Garza-Acosta AC, Mancias-Guerra C, Gonzalez-Llano O, Gonzalez-Cantu GA, Herrera-Rojas MA, Sada-Ovalle I, Gomez-Almaguer D. Cyclosporine A for the Prevention of Ocular Graft versus Host Disease in Allogeneic Hematopoietic Stem Cell Transplant Recipients Is Safe and Feasible. Acta Haematol. 2020;143(5):425-431. doi: 10.1159/000502405. Epub 2019 Sep 10.

  PMID: 31505491 RESULT

• Jung JW, Lee YJ, Yoon SC, Kim TI, Kim EK, Seo KY. Long-term result of maintenance treatment with tacrolimus ointment in chronic ocular graft-versus-host disease. Am J Ophthalmol. 2015 Mar;159(3):519-27.e1. doi: 10.1016/j.ajo.2014.11.035. Epub 2014 Dec 9.

  PMID: 25498356 RESULT

Related Links

• Multicenter prospective validation study for international chronic ocular graft-versus-host disease consensus diagnostic criteria

MeSH Terms

Conditions

Dry Eye Syndromes

Condition Hierarchy (Ancestors)

Lacrimal Apparatus Diseases; Eye Diseases

Central Study Contacts

Olga Graciela Cantú Rodríguez, MD

CONTACT

8186939257; ogcantur@yahoo.com.mx

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Hematology

Model Details: Experimental, prospective, randomized, unblinded.

Study Record Dates

• First Submitted: October 30, 2023
• First Posted: April 4, 2024
• Study Start: August 1, 2023
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: April 8, 2024

Record last verified: 2024-04

Locations

ME (1)