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