Clinical Trial: Azacytidine Prior to in Vivo T-cell Depleted Allo Stem Cell Transplant for Patients With Myeloid Malignancies in CR

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Epigenetic Priming With 5-Azacytidine Prior to in Vivo T-cell Depleted Allogeneic Stem Cell Transplantation for Patients With High Risk Myeloid Malignancies in Morphologic Remission

Brief Summary: The purpose of this study is to determine whether 5-Azacytidine priming before the conditioning regimen for subjects receiving a hematopoietic stem cell transplant is an effective treatment for high risk myeloid malignancies in complete remission (CR).

Detailed Summary:

This open label two-step phase II study is designed to determine the safety and efficacy of epigenetic priming with 5-Azacytidine immediately prior to reduced intensity conditioning for an in vivo T-cell depleted hematopoietic stem cell transplantation for high risk myeloid malignancies in complete remission (CR).

Subjects will be given a five day course of subcutaneous 5-azacytidine, followed by a reduced intensity conditioning regimen of fludarabine and melphalan prior to an allogeneic hematopoietic stem cell transplantation from a related or unrelated HLA matched donor.

The effect of 5-azacytidine on global gene methylation will be assessed. Evaluations for safety, in particular for graft failure, transplant related mortality and acute graft versus host disease will be made on a weekly basis. Efficacy, as defined by disease free survival, will be evaluated with a bone marrow biopsy at the standard time points, which are one-, three-, six-, and twelve-months after transplant and upon clinical suspicion within regular follow-up visits - weekly for the first 3 months, then biweekly for 3 months, then monthly until one-year post-SCT. Thereafter, unless otherwise dictated by the clinical scenario, the follow up visits will be every 3 months.


Sponsor: Weill Medical College of Cornell University

Current Primary Outcome: disease free survival [ Time Frame: 2 years ]

evaluating disease free survival at 6 months, 1 year, 2 years, then overall survival


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Incidence and severity of acute and chronic GVHD [ Time Frame: 1 year ]
    To evaluate the incidence and severity of acute and chronic GVHD after 5-azacytidine priming prior to conditioning for allogeneic stem cell transplantation with Alemtuzumab-based in vivo T-cell depletion in patients with poor risk myeloid malignancies in complete hematologic remission.
  • Engraftment and chimerism patterns [ Time Frame: overall survival ]
    To evaluate engraftment and chimerism patterns after 5-azacytdine primed conditioning for stem cell transplantation with Alemtuzumab-based in vivo T-cell depletion in patients with poor risk myeloid malignancies in complete hematologic remission.
  • evaluate changes in global methylation [ Time Frame: overall survival ]
    To evaluate changes in global gene methylation by 5-azacytidine prior to conditioning for stem cell transplantation with Alemtuzumab-based in vivo T-cell depletion in patients with poor risk myeloid malignancies in complete hematologic remission.


Original Secondary Outcome: Same as current

Information By: Weill Medical College of Cornell University

Dates:
Date Received: February 19, 2015
Date Started: February 13, 2015
Date Completion: July 2021
Last Updated: March 1, 2017
Last Verified: March 2017