Clinical Trial: Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts in Preventing GVHD in Children

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase II Study of Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts for the Prevention of GVHD in Children

Brief Summary: This phase II trial studies how well T cell depleted donor peripheral blood stem cell transplant works in preventing graft-versus-host disease in younger patients with high risk hematologic malignancies. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, 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. Removing a subset of the T cells from the donor cells before transplant may stop this from happening.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Estimate the time to discontinuation of systemic immunosuppression in pediatric recipients of cluster of differentiation 45RA positive (CD45RA+) T cell-depleted peripheral blood stem cell transplant (PBSCT).

II. Estimate the probability of graft failure in pediatric recipients of CD45RA+ T-cell-depleted PBSCT.

SECONDARY OBJECTIVES:

I. Estimate and compare to an appropriate historical cohort the probability of chronic graft-versus-host disease (GVHD) (National Institutes of Health [NIH] criteria) requiring treatment with systemic pharmacological immunosuppression in pediatric patients who receive CD45RA+ T cell depleted PBSC.

II. Estimate the probability of acute GVHD grade II-IV.

III. Estimate the probability of steroid refractory acute GVHD.

IV. Evaluate immune reconstitution.

V. Estimate the probability of transplant-related mortality by day 100.

VI. Estimate the probability of relapse.

OUTLINE:

CONDITIONING REGIMEN: Patients undergo total body irradiation (TBI) twice daily (BID) on days -10 to -7, receive thiotepa intravenously (IV) over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2.

TRANSPLANT: Patients undergo CD34+ enriched, CD45RA+ T cell-depleted allogeneic PBSCT on day 0.

POST-TRANSPLANT IMMUNOSUPPRESSION: Pati
Sponsor: Fred Hutchinson Cancer Research Center

Current Primary Outcome:

  • Graft failure defined as failure to reach an absolute neutrophil count (ANC) of > 500/ul for 3 consecutive days or irreversible decrease in ANC to < 100 after an established donor graft [ Time Frame: Up to 5 years ]
    A true probability of graft failure of 10% will be considered excessive. If there is sufficient evidence to suggest that the true probability of graft failure exceeds 10%, the study will be stopped.
  • Time to ANC of > 1,000/uL [ Time Frame: Up to 5 years ]
  • Time to ANC of > 500/uL [ Time Frame: Up to 5 years ]
  • Time to discontinuation of systemic immunosuppression [ Time Frame: Time from transplant to the final discontinuation of all systemic immune suppression assessed up to 5 years ]
  • Time to platelet count > 20,000/uL for 3 days without transfusion [ Time Frame: Up to 5 years ]
  • Time to platelet count > 50,000/uL for 3 days without transfusion [ Time Frame: Up to 5 years ]


Original Primary Outcome:

  • Time to discontinuation of systemic immunosuppression [ Time Frame: Time from transplant to the final discontinuation of all systemic immune suppression assessed up to 5 years ]
  • Graft failure defined as failure to reach an absolute neutrophil count (ANC) of > 500/µl for 3 consecutive days or irreversible decrease in ANC to < 100 after an established donor graft [ Time Frame: Up to 5 years ]
    A true probability of graft failure of 10% will be considered excessive. If there is sufficient evidence to suggest that the true probability of graft failure exceeds 10%, the study will be stopped.
  • Time to ANC of > 500/uL [ Time Frame: Up to 5 years ]
  • Time to ANC of > 1,000/uL [ Time Frame: Up to 5 years ]
  • Time to platelet count > 20,000/µL for 3 days without transfusion [ Time Frame: Up to 5 years ]
  • Time to platelet count > 50,000/µL for 3 days without transfusion [ Time Frame: Up to 5 years ]


Current Secondary Outcome:

  • Occurrence of chronic GHVD meeting NIH criteria and requiring systemic pharmacological immunosuppression [ Time Frame: Up to 5 years ]
  • Presence of acute GVHD grade III-IV [ Time Frame: Up to day 100 ]
  • Presence of acute GVHD grades II-IV [ Time Frame: Up to day 100 ]
  • Presence of steroid refractory acute GVHD [ Time Frame: Up to day 100 ]
  • Relapse defined by the presence of malignant cells in marrow, peripheral blood, or extramedullary sites by histopathology [ Time Frame: Up to 5 years ]
  • Transplant related mortality defined as mortality in any patient for whom there has not been a diagnosis of relapse [ Time Frame: Up to 5 years ]
  • Use of additional immune suppressive agents other than first line therapy [ Time Frame: Up to 5 years ]


Original Secondary Outcome:

  • Occurrence of chronic GHVD meeting NIH criteria and requiring systemic pharmacological immunosuppression [ Time Frame: Up to 5 years ]
  • Use of additional immune suppressive agents other than first line therapy [ Time Frame: Up to 5 years ]
  • Presence of acute GVHD grades II-IV [ Time Frame: Up to day 100 ]
  • Presence of acute GVHD grade III-IV [ Time Frame: Up to day 100 ]
  • Presence of steroid refractory acute GVHD [ Time Frame: Up to day 100 ]
  • Transplant related mortality defined as mortality in any patient for whom there has not been a diagnosis of relapse [ Time Frame: Up to 5 years ]
  • Relapse defined by the presence of malignant cells in marrow, peripheral blood, or extramedullary sites by histopathology [ Time Frame: Up to 5 years ]


Information By: Fred Hutchinson Cancer Research Center

Dates:
Date Received: May 15, 2013
Date Started: December 17, 2013
Date Completion: January 30, 2022
Last Updated: April 28, 2017
Last Verified: April 2017