This pilot phase II trial studies how well giving vorinostat, tacrolimus, and methotrexate works in preventing graft-versus-host disease (GVHD) after stem cell transplant in patients with hematological malignancies. Vorinostat, tacrolimus, and methotrexate may be an effective treatment for GVHD caused by a bone marrow transplant.
PRIMARY OBJECTIVES: I. To assess the safety and the feasibility of the addition of vorinostat to tacrolimus and methotrexate GVHD prophylaxis. SECONDARY OBJECTIVES: I. To determine day 100 grades 2-4 acute GVHD. II. To determine 1-year overall survival and relapse-free survival. III. To correlate plasma concentrations of inflammatory markers of acute GVHD. IV. To correlate protein acetylation in peripheral blood mononuclear cells before and after administration of vorinostat. OUTLINE: Patients receive vorinostat orally (PO) twice daily (BID) on days -10 to 100. Beginning on day -3, patients receive tacrolimus intravenously (IV) continuously or PO BID (or cyclosporine IV continuously or PO in patients unable to tolerate tacrolimus) with taper on days 100-180.Patients also receive methotrexate IV once daily (QD) on days 1, 3, 6, and 11. After completion of study treatment, patients are followed up periodically for 1 year.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
12
Given PO
Given IV or PO
Given IV or PO
Given IV
Correlative studies
Correlative studies
University of Michigan University Hospital
Ann Arbor, Michigan, United States
The Number of Participants That Experience Grade 2-4 Acute GVHD (Graft Versus Host Disease) by Day 100
The incidence of grade 2-4 acute GVHD (Graft Versus Host Disease) by day 100 Grade 2 GVHD: Maculopapular rash covering 25-50% of BSA (Body Surface Area), bilirubin between 3.1-6 mg/dl, and/ or adult stool output between 1000-1500 ml/day (child between 20-30 ml/kg/day). Grade 3 GVHD: Maculopapular rash covering \>50% of BSA, bilirubin between 6.1-15 mg/dl, and/ or adult stool output \>1500 ml/day (child \>30 ml/kg/day). Grade 4 GVHD: Generalized erythroderma plus bullous formation and desquamation \>5% BSA, bilirubin \>15 mg/dl, and/ or severe abdominal pain with or without ileus, or grossly bloody stool.
Time frame: Day 100
Mean Percent of Planned Dose Administered
The addition of vorinostat to tacrolimus and methotrexate for GVHD prophylaxis will be considered feasible if 60% or more of the planned doses are administered.
Time frame: Up to day 30
The Percentage of Patients Alive Without GVHD or Use of Steroids
The percentage of patients alive without GVHD or use of steroids at 1 year.
Time frame: Up to 1 year
The Percentage of Patients Alive at 1 Year
The percentage of patients alive at 1 year
Time frame: Up to 1 year
The Percentage of Patients With Relapse at 1 Year
Time frame: Up to 1 year
Median Ac-H3 Levels in Patients Treated With Vorinostat and Patients Not Treated With Vorinostat
Median Ac-H3 levels ( depicted as a ratio of ac-H2 optical density (OD) and beta actin OD) were compared in patients treated with Vorinostat to patients not treated with Vorinostat. Optical Density is a dimensionless unit.
Time frame: Up to day 100
Median Plasma Concentration of IL-6 in Patients Treated With Vorinostat and Patients Not Treated With Vorinostat
Median plasma concentration of IL-6 (Interleukin-6 cytokine) was compared in patients treated with Vorinostat to those not treated with Vorinostat.
Time frame: Up to day 100
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