Clinical trial NCT00755040: 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
Official title: Randomized Placebo Controlled Double Blind Study of Restasis Versus Placebo in Primary Prevention of Ocular GVHD After Allogeneic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Myeloproliferative Disorders
Graft Versus Host Disease
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
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
Lead sponsor: Vanderbilt-Ingram Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-09-18
Enrollment: 164
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility 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

Primary outcomes:
measure: Number of Patients That Develop Ocular GVHD While on Study in the Two Arms (Ocular Cyclosporine (Restasis) vs. Placebo)
timeFrame: Up to 2 years after transplantation
Secondary outcomes:
measure: 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.
timeFrame: 1 year after transplant
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Chicago
country: United States
facility: Norwestern Memorial Hospital
state: Illinois
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: M. D. Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Vanderbilt-Ingram Cancer Center
name: Madan Jagasia, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dietrich-Ntoukas T, Cursiefen C, Westekemper H, Eberwein P, Reinhard T, Bertz H, Nepp J, Lawitschka A, Heiligenhaus A, Seitz B, Messmer EM, Meyer-ter-Vehn T, Basara N, Greinix H, Datiles MB, Lee SJ, Pavletic SZ, Wolff D. Diagnosis and treatment of ocular chronic graft-versus-host disease: report from the German-Austrian-Swiss Consensus Conference on Clinical Practice in chronic GVHD. Cornea. 2012 Mar;31(3):299-310. doi: 10.1097/ICO.0b013e318226bf97.