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A Phase I Clinical Trial to Study the Safety of a Sustained-Release Subconjunctival Cyclosporine Implant for Ocular Graft-vs-Host Disease (GVHD1)

Phase 1
9 Years
Not Enrolling
Graft Vs Host Disease

Thank you

Trial Information

A Phase I Clinical Trial to Study the Safety of a Sustained-Release Subconjunctival Cyclosporine Implant for Ocular Graft-vs-Host Disease (GVHD1)

The objective of this randomized pilot study is to investigate the safety and potential
efficacy of a CsA implant in participants with lacrimal gland involvement and aqueous tear
deficiency related to GVHD. Safety will be evaluated in terms of adverse events related to
the implant. Efficacy will be evaluated by changes in Schirmer tear test (with anesthesia).
Secondary efficacy evaluation will include changes in corneal and conjunctival staining
grades, best-corrected visual acuity (BCVA), the Ocular Surface Diseases Index (OSDI),
changes in conjunctival GVHD grades, tear break-up time and meibomian gland dysfunction.

Participants with active systemic GVHD with aqueous tear deficiency associated with lacrimal
gland dysfunction following allogeneic hematopoietic SCT who are nine years of age or older
are eligible for inclusion in this pilot study. The study will involve surgical placement
of the CsA implant into the subconjunctival space adjacent to the lacrimal gland of one eye
in each participant. Participants older than 12 years of age will be randomized to receive
one of two implant release rates. However, all participants under age 12 will not be
randomized and will only be eligible to receive the smaller, lower dose implant. On each
anniversary study visit a participant will be given the opportunity to retain the implant on
an annual basis. This will be based upon the determination of clinical success (defined in
the Study Design section below) combined with a participant's report of symptom improvement.
The Implant will be removed if the Investigator believes the implant is harmful or if the
participant requests the implant to be removed.

Inclusion Criteria


To be eligible for the study each participant must satisfy all of the following inclusion

- Male or female greater than or equal to 9 years of age.

- Must be greater than or equal to 30 days post-hematopoietic stem cell transplantation
(SCT) and have systemic GVHD diagnosed by the transplant physician.

- Must have lacrimal gland dysfunction from GVHD following SCT as defined by Schirmer
tear test score (with anesthesia) of greater than or equal to 1 mm but less than or
equal to 9 mm in both eyes.

- Must have open puncta and no puncta plug placement at the time of enrollment.

- If using topical corticosteroids, must be equal dose in both eyes of less than or
equal to 4 drops per day.

- Topical lubrication using tear substitutes (includes eye drops, gels, and ointments)
are permitted with equal dosing in both eyes.

- Must understand and sign informed consent or assent.

- Must be willing and able to comply with study evaluation and testing schedule.

- Females of childbearing potential and all males must agree to use an effective form
of birth control for duration of the study.

- Females of childbearing potential must have a negative serum pregnancy test at
baseline evaluation.


To be eligible for the study, participants must not satisfy any of the following exclusion

- Use of a topical ophthalmic cyclosporine formulation less than or equal to 30 days
prior to enrollment.

- Diagnosed with active ocular infection.

- History of recurrent herpes keratitis or active disease less than or equal to 6
months prior to enrollment.

- Aqueous tear deficiency or KCS related to previous irradiation, Stevens-Johnson
syndrome, cicatricial pemphigoid, alkali burns, trachoma or Sjogren's syndrome.

- Seropositive for Hepatitis C (i.e. positive anti-HCV antibody) or seropositive for
HIV with testing performed no earlier than 4 months before the date of stem cell

- Diagnosis of active sarcoidosis.

- Use of a drug with anticholinergic activity within less than 4 times the half-life of
the drug prior to enrollment (e.g., carbamazepine [Tegretol (R)] has a half-life of
16-24 hours so must not be used within 4 days of enrollment).

- Use of an investigational drug for eye disease within 30 days of enrollment.

- Known allergy or hypersensitivity to cyclosporine, fluorescein, or lissamine green.

- Uncontrolled systemic disease or serious illness that could, in the investigator's
opinion, interfere with the participant's ability to comply with study therapy,
required follow-up testing, or interfere with interpretation of the study results.

- Pregnant or lactating female.

- Serum creatinine greater than 2.5 mg/dL, absolute neutrophil count (ANC) less than
750/MicroL Platelet count less than 25,000/MicroL, Partial Thromboplastin Time (PTT),
or International Normal Ratio (INR) or Prothrombin Time (PT) exceeding the
institutional upper limit of normal would require review by the Hematologist for
surgical clearance. Hematologist review of the abnormal coagulation value and
approval for surgery must be documented in the medical record prior to the surgical

- Participants that have received total body irradiation or direct eye/orbital
radiation greater than 5000 cGy. (Potential participants will be assessed by a study
clinician to determine that the cause of the dry eye symptoms is due to GVHD and not
radiation. The clinician, in conjunction with the oncology staff as needed, will
also assess the participant's clinical exam and medical history).

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment


United States: Federal Government

Study ID:




Start Date:

October 2004

Completion Date:

March 2011

Related Keywords:

  • Graft Vs Host Disease
  • Dry Eye
  • Lacrimal Gland
  • Tear Deficiency
  • Keratitis Sicca
  • GVHD
  • Ocular GVHD
  • Ocular Graft Vs Host Disease
  • Graft vs Host Disease



National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland  20892