Clinical Trial: Repeat Transplantation for Relapsed or Refractory Hematologic Malignancies Following Prior Transplantation

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: CD45A-Depleted Haploidentical Hematopoietic Progenitor Cell and Natural Killer Cell Transplantation for Hematologic Malignancies Relapsed or Refractory Despite Prior Transplantation

Brief Summary: This pilot phase II trial studies how well a new reduced intensity conditioning regimen that includes haploidentical donor NK cells followed by the infusion of selectively T-cell depleted progenitor cell grafts work in treating younger patients with hematologic malignancies that have returned after or did not respond to treatment with a prior transplant. Giving chemotherapy and natural killer cells before a donor progenitor cell transplant may help stop the growth of cells in the bone marrow, including normal blood-forming cells (progenitor cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's cells. When the healthy progenitor cells from a related donor are infused into the patient they make red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Removing specific T cells from the donor cells before the transplant may prevent this.

Detailed Summary:

PRIMARY OBJECTIVE:

  • To estimate engraftment by day +42 post-transplant in patients who receive CD45RA-depleted haploidentical donor progenitor cell transplantation following reduced intensity conditioning regimen that includes haploidentical natural killer (NK) cells.

SECONDARY OBJECTIVES:

  • Estimate the incidence of malignant relapse, event-free survival, and overall survival at one-year post-transplantation.
  • Estimate incidence and severity of acute and chronic (GvHD).
  • Estimate the rate of transplant related mortality (TRM) in the first 100 days after transplantation.

Blood progenitor cells will be collected from adult donors to be used for transplantation. Donor cells will be processed and filtered in a laboratory at St. Jude using a machine called the CliniMACS™ device, and later infused (transplanted) into the participant through his/her veins.

Participants undergo a conditioning regimen beginning Day 21 prior to progenitor cell transplantation that includes chemotherapy medications and natural killer cells in preparation for transplantation. They will then receive T-cell depleted HPC transplant followed by CD45RA-depleted HPC transplant the following day.


Sponsor: St. Jude Children's Research Hospital

Current Primary Outcome: Percentage of Participants Engrafted by Day 42 Post-transplant [ Time Frame: Day 42 post transplantation ]

To estimate engraftment by day +42 post-transplant in patients who receive CD45RA-depleted haploidentical donor progenitor cell transplantation following reduced intensity conditioning regimen that includes haploidentical NK cells. Engraftment is defined as the first of 3 consecutive tests performed on different days of an ANC ≥ 500/mm^3 with evidence of donor cell engraftment.


Original Primary Outcome: Absolute neutrophil count (ANC) engraftment [ Time Frame: Day 42 post transplantation ]

The primary objective is to estimate ANC engraftment by day 42 in patients who receive CD45RA-depleted haploidentical donor stem cell transplantation following reduced intensity conditioning regimen that includes haploidentical NK cells. ANC engraftment is defined as the first of 3 consecutive tests performed on different days of an ANC ≥ 500/mm3 with evidence of donor cell engraftment.


Current Secondary Outcome:

  • Incidence of Malignant Relapse [ Time Frame: one year post transplantation ]
    The estimate of cumulative incidence of relapse will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event. The number of participants with incidence of malignant relapse is given. Relapse was evaluated using standard WHO criteria for each disease.
  • Event-free Survival (EFS) [ Time Frame: one year post transplantation ]
    The Kaplan-Meier estimate of event-free survival (EFS) along with their standard errors will be calculated using the SAS macro (bmacro251-Excel2007\kme) available in the Department of Biostatistics at St. Jude, where EFS = min (date of last follow-up, date of relapse, date of graft failure, date of death due to any cause) - date of transplant, and all participants surviving at the time of analysis without events will be censored. The number of participants who did not experience any of these events through one year post-transplant is given.
  • Overall Survival (OS) [ Time Frame: one year post transplantation ]
    The Kaplan-Meier estimate of OS along with their standard errors will be calculated using the SAS macro (bmacro251-Excel2007\kme) available in the Department of Biostatistics at St. Jude, where OS = min (date of last follow-up, date of death) - date of transplant and all participants surviving at the time of analysis without events will be censored. The number of participants surviving to one-year post-transplantation is given.
  • Incidence and Severity of Acute GvHD [ Time Frame: 100 days post transplantation ]
    The cumulative incidence of acute GvHD will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event. The severity of acute GvHD. The number of participants with incidence by grade is given. Participants are graded on a scale from 1 to 4, with 1 being mild and 4 being severe.
  • Incidence and Severity of Chronic GvHD [ Time Frame: one year post transplantation ]
    The cumulative incidence of chronic GvHD will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event. The severity of chronic GvHD will be described. Chronic GvHD was evaluated using NIH Consensus Global Severity Scoring." The number of participants with incidence by severity is given.
  • Rate of Transplant-related Mortality (TRM) [ Time Frame: 100 days post transplantation ]
    The cumulative incidence of transplant related mortality will be estimated using Kalbfleisch-Prentice method. Deaths before day 100 because of other reasons are the competing risk events.


Original Secondary Outcome:

  • Incidence of Malignant Relapse [ Time Frame: one year post transplantation ]
    The estimate of cumulative incidence of relapse will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event.
  • Event-free Survival (EFS) [ Time Frame: one year post transplantation ]
    The Kaplan-Meier estimate of event-free survival (EFS) along with their standard errors will be calculated using the SAS macro (bmacro251-Excel2007\kme) available in the Department of Biostatistics at St. Jude, where EFS = min (date of last follow-up, date of relapse, date of graft failure, date of death due to any cause) - date of transplant, and all participants surviving at the time of analysis without events will be censored.
  • Overall Survival (OS) [ Time Frame: one year post transplantation ]
    The Kaplan-Meier estimate of OS along with their standard errors will be calculated using the SAS macro (bmacro251-Excel2007\kme) available in the Department of Biostatistics at St. Jude, where OS = min (date of last follow-up, date of death) - date of transplant and all participants surviving at the time of analysis without events will be censored.
  • Incidence and Severity of GvHD [ Time Frame: 100 days (acute) and one year (chronic) post transplantation ]
    The cumulative incidence of acute and chronic GvHD will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event. The severity of acute GvHD and chronic GvHD will be described.
  • Rate of Transplant-related Mortality (TRM) [ Time Frame: 100 days post transplantation ]
    The cumulative incidence of transplant related mortality will be estimated using Kalbfleisch-Prentice method. Deaths before day 100 because of other reasons are the competing risk events.


Information By: St. Jude Children's Research Hospital

Dates:
Date Received: October 3, 2014
Date Started: October 2014
Date Completion:
Last Updated: November 2, 2016
Last Verified: September 2016