Chronic Myeloproliferative Disorders, Graft Versus Host Disease, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic/Myeloproliferative Neoplasms, Myelodysplastic Syndromes
Conditions
Keywords
graft versus host disease, stage III adult Burkitt lymphoma, stage III adult diffuse large cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage III adult Hodgkin lymphoma, stage III adult immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage III mantle cell lymphoma, stage III marginal zone lymphoma, stage III small lymphocytic lymphoma, stage IV adult Burkitt lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult Hodgkin lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV mantle cell lymphoma, stage IV marginal zone lymphoma, stage IV small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, noncontiguous stage II adult Burkitt lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse mixed cell lymphoma, noncontiguous stage II adult diffuse small cleaved cell lymphoma, noncontiguous stage II adult immunoblastic large cell lymphoma, noncontiguous stage II adult lymphoblastic lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, noncontiguous stage II grade 3 follicular lymphoma, noncontiguous stage II mantle cell lymphoma, noncontiguous stage II marginal zone lymphoma, noncontiguous stage II small lymphocytic lymphoma, accelerated phase chronic myelogenous leukemia, adult acute lymphoblastic leukemia in remission, adult acute myeloid leukemia in remission, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), atypical chronic myeloid leukemia, BCR-ABL negative, blastic phase chronic myelogenous leukemia, chronic myelomonocytic leukemia, chronic phase chronic myelogenous leukemia, secondary acute myeloid leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, chronic eosinophilic leukemia, primary myelofibrosis, chronic neutrophilic leukemia, de novo myelodysplastic syndromes, myelodysplastic/myeloproliferative neoplasm, unclassifiable, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma
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.
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.
Interventions
Given as eye drops
OTHERplacebo
Given as eye drops
Sponsors
National Cancer Institute (NCI)
Vanderbilt-Ingram Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ocular Cyclosporine (Restasis) 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 | 83 |
| Placebo Patients receive placebo ophthalmic drops in each eye twice daily for up to 1 year after transplant.
placebo: Given as eye drops | 81 |
| Total | 164 |
Baseline characteristics
| Characteristic | Placebo | Ocular Cyclosporine (Restasis) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 2 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 75 Participants | 81 Participants | 156 Participants |
| Age, Continuous | 49 Years STANDARD_DEVIATION 11.707 | 49 Years STANDARD_DEVIATION 12.458 | 49 Years STANDARD_DEVIATION 12.062 |
| Region of Enrollment United States | 81 participants | 83 participants | 164 participants |
| Sex: Female, Male Female | 39 Participants | 34 Participants | 73 Participants |
| Sex: Female, Male Male | 42 Participants | 49 Participants | 91 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 49 / 83 | 18 / 81 |
| serious Total, serious adverse events | 3 / 83 | 7 / 81 |
Outcome results
Primary
Number of Patients That Develop Ocular GVHD While on Study in the Two Arms (Ocular Cyclosporine (Restasis) vs. Placebo)
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
Population: Number of patients that develop ocular GVHD while on study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I | Number of Patients That Develop Ocular GVHD While on Study in the Two Arms (Ocular Cyclosporine (Restasis) vs. Placebo) | 9 participants |
| Arm II | Number of Patients That Develop Ocular GVHD While on Study in the Two Arms (Ocular Cyclosporine (Restasis) vs. Placebo) | 8 participants |
p-value: >0.99Fisher Exact
Secondary
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.
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
Population: Not collected/analysed due to staffing constraints