Clinical Trial: Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts From HLA-Matched Related and Unrelated Donors in Preventing GVHD

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

Official Title: A Phase II Study Evaluating Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts From HLA-Matched Related and Unrelated Donors for Prevention of GVHD

Brief Summary: This phase II trial studies how well selective T cell depletion works in preventing graft-versus-host disease (GVHD) in patients with acute lymphocytic leukemia, acute myeloid leukemia, or chronic myelogenous leukemia undergoing donor peripheral blood stem cell transplant. 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. To estimate the probability of developing chronic GHVD among patients who receive naive T cell (TN)-depleted peripheral blood stem cell transplant (PBSCT) in each of the following groups: a) Arm A: patients who receive TN-depleted peripheral blood stem cells (PBSC) from a human leukocyte antigens (HLA) matched related donor (MRD) following high-intensity myeloablative conditioning (total body irradiation [TBI] 1320 cGy, thiotepa, fludarabine phosphate [fludarabine]) and pharmacological immunosuppression with tacrolimus and methotrexate; b) Arm B: patients who receive TN-depleted PBSC from a MRD following lower-intensity myeloablative conditioning (TBI 400 cGy, thiotepa, fludarabine and cyclophosphamide) and pharmacological immunosuppression with tacrolimus and mycophenolate mofetil (MMF); c) Arm C: patients who receive TN-depleted PBSC from a HLA-matched unrelated donor (MUD) following high-intensity myeloablative conditioning (TBI 1320 cGy, thiotepa, fludarabine) and pharmacological immunosuppression with tacrolimus and methotrexate; d) Arm D: patients who receive TN-depleted PBSC from a MUD following lower-intensity myeloablative conditioning (TBI 400 cGy, thiotepa, fludarabine and cyclophosphamide) and pharmacological immunosuppression with tacrolimus and MMF.

II. To estimate the probability of acute (a)GVHD grade II-IV following TN-depleted (TND) PBSCT with tacrolimus and methotrexate (Arm A) or MMF (Arm B) GVHD prophylaxis in MRD recipients.

III. Estimate the rate of aGVHD grade II-IV following TND PBSCT with tacrolimus and methotrexate (Arm C) or MMF (Arm D) prophylaxis in recipients of MUD hematopoietic cell transplantation (HCT).

IV. Estimate the probability of graft failure in recipients of CD
Sponsor: Fred Hutchinson Cancer Research Center

Current Primary Outcome:

  • Graft failure, defined operationally as failure to reach an absolute neutrophil count (ANC) of > 500/ul for 3 consecutive days by day 28 or irreversible decrease in ANC to < 100 after an established donor graft [ Time Frame: Up to day 28 ]
  • Occurrence of chronic GHVD, defined operationally as the occurrence of compatible symptoms meeting National Institutes of Health criteria and requiring systemic pharmacological immunosuppression [ Time Frame: Up to 5 years ]
    MRD-high intensity (Arm A), MRD-lower intensity (Arm B), MUD-high intensity (Arm C) and MUD-lower intensity (Arm D) cohorts will be analyzed separately.
  • Presence of acute GVHD grades II-IV, defined operationally as the occurrence of compatible symptoms or signs in the skin, gastrointestinal tract, or liver [ Time Frame: Up to day 100 ]
  • Requirement for secondary systemic therapy for acute GVHD management [ Time Frame: Up to day 100 ]
  • Requirement of immunosuppression after transplant [ Time Frame: At 2 years after transplant ]
  • Time to completion of all immunosuppression [ Time Frame: Up to 5 years ]
  • Time to completion of prednisone [ Time Frame: Up to 5 years ]
  • Use of additional immune suppressive agents other than first line therapy (prednisone and tacrolimus/cyclosporine) [ Time Frame: Up to 5 years ]


Original Primary Outcome:

  • Occurrence of chronic GHVD, defined operationally as the occurrence of compatible symptoms meeting National Institutes of Health criteria and requiring systemic pharmacological immunosuppression [ Time Frame: Up to 5 years ]
  • Use of additional immune suppressive agents other than first line therapy (prednisone and tacrolimus/cyclosporine) [ Time Frame: Up to 5 years ]
  • Time to completion of prednisone [ Time Frame: Up to 5 years ]
  • Time to completion of all immunosuppression [ Time Frame: Up to 5 years ]
  • Requirement of immunosuppression after transplant [ Time Frame: At 2 years after transplant ]
  • Presence of acute GVHD grades II-IV, defined operationally as the occurrence of compatible symptoms or signs in the skin, gastrointestinal tract, or liver prior to day +100 [ Time Frame: Up to day 100 ]
  • Requirement for secondary systemic therapy for acute GVHD management [ Time Frame: Up to day 100 ]
  • Graft failure, defined operationally as failure to reach an absolute neutrophil count (ANC) of > 500/ul for 3 consecutive days by day 28 or irreversible decrease in ANC to < 100 after an established donor graft [ Time Frame: Up to day 28 ]


Current Secondary Outcome:

  • Chimerism analysis [ Time Frame: Up to 360 days ]
  • Relapse, defined by the presence of malignant cells in marrow, peripheral blood, or extramedullary sites by histopathology [ Time Frame: Up to 5 years ]
  • Time to ANC of > 1,000/uL on the first of three consecutive test results [ Time Frame: Up to 5 years ]
  • Time to ANC of > 500/uL on the first of three consecutive days [ Time Frame: 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 ]
  • 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 ]


Original Secondary Outcome:

  • Time to ANC of > 500/uL on the first of three consecutive days [ Time Frame: Up to 5 years ]
  • Time to ANC of > 1,000/uL on the first of three consecutive test results [ Time Frame: 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 ]
  • Chimerism analysis [ Time Frame: Up to 360 days ]
  • 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 ]


Information By: Fred Hutchinson Cancer Research Center

Dates:
Date Received: August 18, 2014
Date Started: February 2015
Date Completion:
Last Updated: March 29, 2017
Last Verified: March 2017