Cyclosporine Eye Drops in Preventing Graft-Versus-Host Disease of the Eye in Patients Who Have Undergone Donor Stem Cell Transplant for Hematologic Cancer or Bone Marrow Failure Disorder
Study Details
Study Description
Brief Summary
RATIONALE: Cyclosporine eye drops may prevent graft-versus-host disease of the eye in patients who have undergone donor stem cell transplant for hematologic cancer or bone marrow failure disorder.
PURPOSE: This randomized phase I trial is studying how well cyclosporine eye drops work in preventing graft-versus-host disease of the eye in patients who have undergone donor stem cell transplant for hematologic cancer or bone marrow failure disorder.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
OBJECTIVES:
Primary
- To assess the efficacy of cyclosporine ophthalmic emulsion (Restasis®) in the prevention of ocular graft-versus-host disease in patients who have undergone allogeneic stem cell transplantation for hematologic malignancies or bone marrow failure disorders.
Secondary
- To correlate the Ocular Surface Disease Index with clinical ophthalmologic examination.
OUTLINE: This is a multicenter study. Patients are stratified according to age, type of transplant (related vs unrelated), and intensity of transplant (ablative vs other). Patients are randomized to 1 of 2 treatment arms.
-
Arm I: Patients receive cyclosporine ophthalmic emulsion (Restasis®) drops in each eye twice daily for up to 1 year after transplant.
-
Arm II: Patients receive placebo ophthalmic drops in each eye twice daily for up to 1 year after transplant.
Patients in both arms may also receive artificial tear drops at least twice daily as clinically necessary.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Ocular Cyclosporine (Restasis) Patients receive cyclosporine ophthalmic emulsion (Restasis®) drops in each eye twice daily for up to 1 year after transplant. |
Drug: cyclosporine ophthalmic emulsion
Given as eye drops
|
| Placebo Comparator: Placebo Patients receive placebo ophthalmic drops in each eye twice daily for up to 1 year after transplant. |
Other: placebo
Given as eye drops
|
Outcome Measures
Primary Outcome Measures
- Number of Patients That Develop Ocular GVHD While on Study in the Two Arms (Ocular Cyclosporine (Restasis) vs. Placebo) [Up to 2 years after transplantation]
Data analysis will be performed on an intention-to-treat basis. Logistic regression will be used to estimate the odds ratio and 95% confidence interval of the two treatment groups with the adjustment of baseline covariates. Outcome comparisons for categorical/dichotomous variables will be assessed by 2 test or Fisher's exact test where expected cell frequencies were <5; continuous variables will be compared by X/2 test or by Mann-Whitney U test where the data are strongly skewed.
Secondary Outcome Measures
- Numerical Score of Ocular Surface Disease Index (OSDI) and Development or Lack of Ocular GVHD (by Ophthalmologic Examination) as Measured by Odds Ratio in a Linear Regression Model. [1 year after transplant]
OSDI is a patient reported questionnaire consisting of 12 questions which are scored from 0 to 4. The total scored is computed and depending on the number of questions answered scores are computed which are then categorized into mild, moderate or severe dry eye symptoms. This tool should adequately reflect the morbidity of the dry eye symptoms.
Eligibility Criteria
Criteria
Inclusion criteria:
-
Age greater than or equal to 18 years at time of enrollment
-
Day 80-120 after first allogeneic stem cell transplant for hematologic malignancies or -marrow failure disorder at time of study enrollment
-
Signed informed consent
-
Willing to adhere to protocol requirements
Exclusion criteria:
-
history of non-compliance
-
diagnosis of ocular GVHD at time of study enrollment
-
documented dry eye prior to onset of stem cell transplant
-
significant non- GVHD ocular problems that precludes participation in study
-
life expectancy of lesser than 6 months at time of enrollment (viz. grade 4 acute GVHD, florid progression or relapse of underlying disease)
-
history of documented ocular infections prior to stem cell transplant or during transplant (i.e. history of herpetic keratitis)
-
females who are pregnant or breastfeeding
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Stanford University | Palo Alto | California | United States | 94305 |
| 2 | Norwestern Memorial Hospital | Chicago | Illinois | United States | 60611 |
| 3 | Vanderbilt-Ingram Cancer Center | Nashville | Tennessee | United States | 37232-6838 |
| 4 | M. D. Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 5 | Fred Hutchinson Cancer Research Center | Seattle | Washington | United States | 989109 |
Sponsors and Collaborators
- Vanderbilt-Ingram Cancer Center
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Madan Jagasia, MD, Vanderbilt-Ingram Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- VICC BMT 0766
- P30CA068485
- VU-VICC-BMT-0766
- VU-080786
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Arm I | Arm II |
|---|---|---|
| Arm/Group Description | Patients receive cyclosporine ophthalmic emulsion (Restasis®) drops in each eye twice daily for up to 1 year after transplant. cyclosporine ophthalmic emulsion: Given as eye drops | Patients receive placebo ophthalmic drops in each eye twice daily for up to 1 year after transplant. placebo: Given as eye drops |
| Period Title: Overall Study | ||
| STARTED | 83 | 81 |
| COMPLETED | 40 | 47 |
| NOT COMPLETED | 43 | 34 |
Baseline Characteristics
| Arm/Group Title | Ocular Cyclosporine (Restasis) | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Patients receive cyclosporine ophthalmic emulsion (Restasis®) drops in each eye twice daily for up to 1 year after transplant. cyclosporine ophthalmic emulsion: Given as eye drops | Patients receive placebo ophthalmic drops in each eye twice daily for up to 1 year after transplant. placebo: Given as eye drops | Total of all reporting groups |
| Overall Participants | 83 | 81 | 164 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
81
97.6%
|
75
92.6%
|
156
95.1%
|
| >=65 years |
2
2.4%
|
6
7.4%
|
8
4.9%
|
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
49
(12.458)
|
49
(11.707)
|
49
(12.062)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
34
41%
|
39
48.1%
|
73
44.5%
|
| Male |
49
59%
|
42
51.9%
|
91
55.5%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
83
100%
|
81
100%
|
164
100%
|
Outcome Measures
| Title | Number of Patients That Develop Ocular GVHD While on Study in the Two Arms (Ocular Cyclosporine (Restasis) vs. Placebo) |
|---|---|
| Description | Data analysis will be performed on an intention-to-treat basis. Logistic regression will be used to estimate the odds ratio and 95% confidence interval of the two treatment groups with the adjustment of baseline covariates. Outcome comparisons for categorical/dichotomous variables will be assessed by 2 test or Fisher's exact test where expected cell frequencies were <5; continuous variables will be compared by X/2 test or by Mann-Whitney U test where the data are strongly skewed. |
| Time Frame | Up to 2 years after transplantation |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of patients that develop ocular GVHD while on study |
| Arm/Group Title | Arm I | Arm II |
|---|---|---|
| Arm/Group Description | Patients receive cyclosporine ophthalmic emulsion (Restasis®) drops in each eye twice daily for up to 1 year after transplant. cyclosporine ophthalmic emulsion: Given as eye drops | Patients receive placebo ophthalmic drops in each eye twice daily for up to 1 year after transplant. placebo: Given as eye drops |
| Measure Participants | 83 | 81 |
| Number [participants] |
9
10.8%
|
8
9.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm I, Arm II |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.99 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.11 | |
| Confidence Interval |
(2-Sided) 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Numerical Score of Ocular Surface Disease Index (OSDI) and Development or Lack of Ocular GVHD (by Ophthalmologic Examination) as Measured by Odds Ratio in a Linear Regression Model. |
|---|---|
| Description | OSDI is a patient reported questionnaire consisting of 12 questions which are scored from 0 to 4. The total scored is computed and depending on the number of questions answered scores are computed which are then categorized into mild, moderate or severe dry eye symptoms. This tool should adequately reflect the morbidity of the dry eye symptoms. |
| Time Frame | 1 year after transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Not collected/analysed due to staffing constraints |
| Arm/Group Title | Arm I | Arm II |
|---|---|---|
| Arm/Group Description | Patients receive cyclosporine ophthalmic emulsion (Restasis®) drops in each eye twice daily for up to 1 year after transplant. cyclosporine ophthalmic emulsion: Given as eye drops | Patients receive placebo ophthalmic drops in each eye twice daily for up to 1 year after transplant. placebo: Given as eye drops |
| Measure Participants | 0 | 0 |
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Arm I | Arm II | ||
| Arm/Group Description | Patients receive cyclosporine ophthalmic emulsion (Restasis®) drops in each eye twice daily for up to 1 year after transplant. cyclosporine ophthalmic emulsion: Given as eye drops | Patients receive placebo ophthalmic drops in each eye twice daily for up to 1 year after transplant. placebo: Given as eye drops | ||
All Cause Mortality |
||||
| Arm I | Arm II | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Arm I | Arm II | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/83 (3.6%) | 7/81 (8.6%) | ||
| Blood and lymphatic system disorders | ||||
| Blood/Bone Marrow | 3/83 (3.6%) | 3 | 4/81 (4.9%) | 4 |
| Blood/Bone Marrow Other | 0/83 (0%) | 0 | 2/81 (2.5%) | 2 |
| General disorders | ||||
| Multi-organ failure | 0/83 (0%) | 0 | 1/81 (1.2%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Arm I | Arm II | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 49/83 (59%) | 18/81 (22.2%) | ||
| Eye disorders | ||||
| Burning | 31/83 (37.3%) | 49 | 9/81 (11.1%) | 18 |
| Red eye | 13/83 (15.7%) | 13 | 18/81 (22.2%) | 22 |
| Discharge | 9/83 (10.8%) | 13 | 8/81 (9.9%) | 8 |
| Excessive tearing | 14/83 (16.9%) | 20 | 15/81 (18.5%) | 21 |
| Eye pain | 5/83 (6%) | 6 | 6/81 (7.4%) | 6 |
| Foreign Body Sensation | 5/83 (6%) | 5 | 8/81 (9.9%) | 9 |
| Itching | 16/83 (19.3%) | 20 | 9/81 (11.1%) | 13 |
| Stinging | 17/83 (20.5%) | 22 | 8/81 (9.9%) | 9 |
| Visual disturbance | 13/83 (15.7%) | 14 | 18/81 (22.2%) | 23 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Madan Jagasia, M.D. |
|---|---|
| Organization | Vanderbilt Ingram Cancer Center |
| Phone | (615) 936-8422 |
| madan.jagasia@vanderbilt.edu |
- VICC BMT 0766
- P30CA068485
- VU-VICC-BMT-0766
- VU-080786