Clinical Trial: Vorinostat, Tacrolimus, and Methotrexate in Preventing GVHD After Stem Cell Transplant in Patients With Hematological Malignancies
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: A Pilot Trial of Vorinostat Plus Tacrolimus and Methotrexate to Prevent Graft Versus Host Disease Following Unrelated Donor Hematopoietic Stem Cell Transplantation
Brief Summary: 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.
Detailed Summary:
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.
Sponsor: National Cancer Institute (NCI)
Current Primary Outcome: The Number of Participants That Experience Grade 2-4 Acute GVHD (Graft Versus Host Disease) by Day 100 [ Time Frame: 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.
Original Primary Outcome: Feasibility, defined as successful administration of at least 60% of planned doses between day -10 and day 30 for an individual study patient [ Time Frame: Up to day 30 ]
Current Secondary Outcome:
- Mean Percent of Planned Dose Administered [ Time Frame: Up to day 30 ]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.
- Steroid-free Survival [ Time Frame: Up to 1 year ]Estimated with Kaplan-Meier methods.
- Overall Survival [ Time Frame: Up to 1 year ]Estimated with Kaplan-Meier methods.
- Relapse [ Time Frame: Up to 1 year ]Estimated with Kaplan-Meier methods.
- Histone Acetylation in Peripheral Blood Stem Cells (PBMC) [ Time Frame: Up to day 100 ]Summarized with means and 95% confidence intervals.
- Plasma Concentrations of Inflammatory GVHD Markers [ Time Frame: Up to day 100 ]Summarized with means and 95% confidence intervals.
Original Secondary Outcome:
- Incidence of grade 2-4 acute GVHD [ Time Frame: Day 100 ]Estimated with Kaplan-Meier methods.
- Steroid-free Survival [ Time Frame: Up to 1 year ]Estimated with Kaplan-Meier methods.
- Overall Survival [ Time Frame: Up to 1 year ]Estimated with Kaplan-Meier methods.
- Relapse [ Time Frame: Up to 1 year ]Estimated with Kaplan-Meier methods.
- Histone Acetylation in Peripheral Blood Stem Cells (PBMC) [ Time Frame: Up to day 100 ]Summarized with means and 95% confidence intervals.
- Plasma Concentrations of Inflammatory GVHD Markers [ Time Frame: Up to day 100 ]Summarized with means and 95% confidence intervals.
Information By: National Cancer Institute (NCI)
Dates:
Date Received: February 7, 2013
Date Started: June 2013
Date Completion:
Last Updated: October 13, 2015
Last Verified: June 2014