Clinical Trial: Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

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

Official Title: Nonmyeloablative Hematopoietic Cell Transplantation (HCT) for Patients With Hematologic Malignancies Using Related, HLA-Haploidentical Donors: A Phase II Trial of Peripheral Blood Stem Cells (PBSC) as

Brief Summary: This phase II trial studies how well donor peripheral blood stem cell (PBSC) transplant works in treating patients with hematologic malignancies. Cyclophosphamide when added to tacrolimus and mycophenolate mofetil is safe and effective in preventing severe graft-versus-host disease (GVHD) in most patients with hematologic malignancies undergoing transplantation of bone marrow from half-matched (haploidentical) donors. This approach has extended the transplant option to patients who do not have matched related or unrelated donors, especially for patients from ethnic minority groups. The graft contains cells of the donor's immune system which potentially can recognize and destroy the patient's cancer cells (graft-versus-tumor effect). Rejection of the donor's cells by the patient's own immune system is prevented by giving low doses of chemotherapy (fludarabine phosphate and cyclophosphamide) and total-body irradiation before transplant. Patients can experience low blood cell counts after transplant. Using stem cells and immune cells collected from the donor's circulating blood may result in quicker recovery of blood counts and may be more effective in treating the patient's disease than using bone marrow.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To demonstrate that use of PBSC in place of marrow as the source of lymphocytes and stem cells for nonmyeloablative transplants from related, haploidentical donors will not result in unacceptable rates of high-grade acute or chronic GVHD, non-relapse mortality or relapse compared to historical data on nonmyeloablative transplants from unrelated donors.

SECONDARY OBJECTIVES:

I. Estimates of the rates of neutrophil and platelet recovery, number of red blood cell (RBC) and platelet transfusions, incidences of graft failure, transplant-related toxicities, disease-free survival and overall survival.

OUTLINE:

Patients receive fludarabine intravenously (IV) over 30-60 minutes daily on days -6 through -2 and cyclophosphamide IV over 1-2 hours on days -6, -5, and 3-4. Patients undergo total-body irradiation on day -1. Patients undergo donor peripheral blood stem cell transplant on day 0. Patients then receive tacrolimus IV once daily or orally (PO) twice daily (BID) on days 5-180 (may be continued if active GVHD is present), mycophenolate mofetil IV or PO thrice daily (TID) on days 5-35 (may be continued if GVHD present), and filgrastim IV beginning on day 5 until the absolute neutrophil count (ANC) is >= 1,000/mm^3 for three consecutive days.

Treatment continues in the absence of disease progression or unacceptable toxicity.


Sponsor: Fred Hutchinson Cancer Research Center

Current Primary Outcome:

  • Cumulative incidence of non-relapse mortality, defined as death without evidence of disease progression [ Time Frame: Up to 1 year ]
  • Incidence of chronic GVHD [ Time Frame: Up to 1 year post-transplant ]
    Scored according to the National Cancer Institute criteria. The time to onset of limited and extensive chronic GVHD will be recorded.
  • Incidence of grades III/IV acute GVHD [ Time Frame: At day 84 ]
    Grading determined by organ system stages. Grade III/IV acute GVHD is defined as skin: stage IV, liver: stages II-IV, and/or gastrointestinal tract: stages II-IV.
  • Relapse of malignancy after transplantation [ Time Frame: Up to 7 years ]
    Defined by either morphological or cytogenetic evidence of acute leukemia consistent with pre-transplant features, or radiologic evidence of lymphoma progression. When in doubt, the diagnosis of recurrent or progressive lymphoma should be documented by tissue biopsy.


Original Primary Outcome: Incidence of severe acute and chronic GvHD, nonrelapse-related deaths and relapse [ Time Frame: Day +84 ]

Current Secondary Outcome:

  • Donor cell engraftment [ Time Frame: Up to day 84 post-transplant ]
    Donor chimerism in the T-cell (CD3-positive) and granulocyte (CD33-positive) fractions of sorted peripheral blood greater or equal to 50%.
  • Infections [ Time Frame: Up to 7 years ]
    Reported by anatomic site, date of onset, organism and resolution, if any.
  • Neutrophil recovery [ Time Frame: Up to day 84 post-transplant ]
    Achievement of an ANC greater or equal to 500/mm^3 for three consecutive measurements on different days. The first of the three days will be designated the day of neutrophil recovery.
  • Platelet recovery [ Time Frame: Up to day 84 post-transplant ]
    The first day of a sustained platelet count > 20,000/mm^3 with no platelet transfusions in the preceding seven days.
  • Primary graft failure [ Time Frame: At day 84 ]
    Defined as < 5% donor cluster of differentiation (CD)3 chimerism. Chimerism will be measured by short tandem repeat-polymerase chain reaction on peripheral blood sorted into CD3 and CD33 cell fractions.
  • Progression-free survival [ Time Frame: Time interval to relapse/recurrence, to death or to last follow-up, assessed for up to 7 years ]
    Defined as the minimum time interval to relapse/recurrence, to death or to last follow-up.
  • Secondary graft failure [ Time Frame: Up to day 84 post-transplant ]
    Initial recovery followed by neutropenia with < 5% donor chimerism. If no chimerism assays were performed and ANC is less than 500/mm^3, then it will be counted as a secondary graft failure.
  • Toxicity of treatment regimen [ Time Frame: Up to day 90 ]
    Assessed by Common Terminology Criteria for Adverse Events version 3.0. The incidence of all adverse events greater or equal to grade 3 will be determined.


Original Secondary Outcome:

  • Neutrophil recovery
  • Primary graft failure [ Time Frame: Day +84 ]
  • Secondary graft failure
  • Platelet recovery
  • Donor cell engraftment [ Time Frame: Day >= 84 after transplantation and day +28 ]
  • Progression-free survival
  • Infections
  • Toxicity as assessed by CTCAE version 3.0


Information By: Fred Hutchinson Cancer Research Center

Dates:
Date Received: December 8, 2009
Date Started: February 2010
Date Completion:
Last Updated: January 9, 2017
Last Verified: January 2017