A Phase 1/2 interventional study of Cyclosporine ophthalmic solution 0.1% and Tacrolimus ophthalmic ointment 0.03% in Ocular Graft-versus-host Disease, sponsored by Hospital Universitario Dr. Jose E. Gonzalez. Recruiting at 1 site in Mexico. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-04-08.
Sponsored by Hospital Universitario Dr. Jose E. Gonzalez · Phase 1/2, Interventional, and Prevention
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.
After being informed about the study and potential risks, all patients giving written informed consent will be assigned a participant number to anonymize their data and collect information, including age, sex, diagnosis, stage of disease, type of procedure, and conditioning chemotherapy. Additionally, an ophthalmology evaluation will be conducted in the Ophthalmology Department of the University Hospital of the U.A.N.L. by the study team of ophthalmologists, following a standardized method and using a worksheet for dry eye and ocular surface evaluation.
Participants will be randomized to receive either treatment arm A (cyclosporine eye drops) or treatment arm B (tacrolimus ointment) through a stratified method. After the hematopoietic stem cell transplant (HSCT), information will be collected, such as the transplant details (e.g., number of cluster of differentiation 34 [CD34] cells infused, cell source, and any complications during the procedure) and medications used for the systemic GVHD prophylaxis, as well as the graft date. In addition to the standard systemic management protocol for GVHD prevention of the transplant program of the Hematology Service of the Hospital University U.A.N.L. cyclosporine or tacrolimus will be administered to participants once grafting is demonstrated, defined as the presence in the blood count of a neutrophil count that is equal to or greater than to 500/mm3 and platelet count equal to or greater than 20,000/mm3.
Ophthalmological evaluations will be carried out at the initial visit (before the bone marrow transplant) and scheduled subsequent visits: at the time of transplant graft (variable depending on the type of transplant, between days +10 and +21 approximately), and 3, 6, 9, and 12 months from the start of treatment (day of graft). Also, they will be evaluated during all follow-up visits to the transplant department of the Hematology Service, assessing adherence and tolerance to the medication through direct questioning. The severity of ocular GVHD will be established based on the NIH criteria and the severity criteria of the international consensus on the severity of chronic ocular GVHD (ICCGVHD)
Ophthalmological variables to be evaluated
806 studies on the registry are indexed under Graft vs Host Disease; 138 are open to participants now.
This study's planned enrollment of 60 is above the median of 35 across 637 interventional studies indexed under Graft vs Host Disease.
Browse Graft vs Host Disease studies →Hospital Universitario Dr. Jose E. Gonzalez is the lead sponsor of 79 studies on the registry; 11 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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 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%
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
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
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.
Time frame: 2.5 years
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.
Severity graded from 0 to 3 as follows: 0: No symptoms; 1: mild dry eye symptoms not affecting activity of daily living (requiring eye drops ≤3 x per day); 2: Moderate dry eye symptoms partially affecting activity of daily living (requiring eye drops \>3 x per day or punctal plugs) WITHOUT new vision impairment due to keratoconjunctivitis sicca; 3: Severe dry eye symptoms significantly affecting activity of daily living (special eyewear to relieve pain) OR unable to work because of ocular symptoms OR loss of vision due to keratoconjunctivitis sicca. Note: higher scores mean a worse outcome.
Time frame: 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
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.
Time frame: 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.
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.
Time frame: 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.
Severity graded from 0 to 3 as follows: 0: No symptoms; 1: mild dry eye symptoms not affecting activity of daily living (requiring eye drops ≤3 x per day); 2: Moderate dry eye symptoms partially affecting activity of daily living (requiring eye drops \>3 x per day or punctal plugs) WITHOUT new vision impairment due to keratoconjunctivitis sicca; 3: Severe dry eye symptoms significantly affecting activity of daily living (special eyewear to relieve pain) OR unable to work because of ocular symptoms OR loss of vision due to keratoconjunctivitis sicca. Note: higher scores mean a worse outcome.
Time frame: 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.
Severity graded from 0 to 3 as follows: 0: No symptoms; 1: mild dry eye symptoms not affecting activity of daily living (requiring eye drops ≤3 x per day); 2: Moderate dry eye symptoms partially affecting activity of daily living (requiring eye drops \>3 x per day or punctal plugs) WITHOUT new vision impairment due to keratoconjunctivitis sicca; 3: Severe dry eye symptoms significantly affecting activity of daily living (special eyewear to relieve pain) OR unable to work because of ocular symptoms OR loss of vision due to keratoconjunctivitis sicca. Note: higher scores mean a worse outcome.
Time frame: 10 years
Number of participants requiring adjuvant treatment for ocular GVHD in patients receiving prophylactic tacrolimus or cyclosporine for ocular GVHD.
e.g topical corticosteroids
Time frame: 2.5 years
Prevalence of Dry Eye Disease prior to the HSCT.
Evaluation of dry eye symptoms with the ocular surface disease index (OSDI), National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25), tear breakup time, schirmer test.
Time frame: 2.5
Subtypes of Dry Eye Disease prior to the HSCT
Evaluation of dry eye symptoms with the ocular surface disease index (OSDI), National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25), tear breakup time, schirmer test.
Time frame: 2.5
Number of participants requiring adjuvant treatments for the Dry Eye Disease
e.g.eye lubricant, artificial tears, autologous serum or autologous platelet-rich plasma in drops.
Time frame: 2.5 years
Incidence of other manifestations of acute and chronic GVHD, local or systemic, in patients receiving prophylactic treatment for ocular GVHD.
With The National Institutes of Health (NIH) consensus criteria used to diagnose GVHD
Time frame: 2.5 years
Number of participants with topical tacrolimus related adverse events as assessed by a questionnaire for evaluation of adverse drug events
Variables: frequency and severity (0-100) of burning sensation, pain, itching, discomfort, blurred vision, foreign body sensation, others.
Time frame: 1 year
Number of participants with topical cyclosporine related adverse events as assessed by a questionnaire for evaluation of adverse drug events
Variables: frequency and severity (0-100) of burning sensation, pain, itching, discomfort, blurred vision, foreign body sensation, others.
Time frame: 1 year
Incidence of ocular GVHD in patients receiving prophylactic treatment for ocular GVHD.
Assessed by the Ocular Graft Versus Host Disease diagnostic criteria and grading scale according to the NIH criteria 2014 and the International Consensus Criteria on chronic ocular graft versus host disease (ICCGVHD)
Time frame: 2.5 years
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Hospital Universitario Dr. Jose E. Gonzalez