Clinical Trial: Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase II Study to Evaluate the Efficacy of Posttransplant Cyclophosphamide for Prevention of Chronic Graft-versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation

Brief Summary: This phase II trial studies how well cyclophosphamide works in preventing chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplant in patients with hematological malignancies. Giving chemotherapy and total-body irradiation before transplantation helps stop the growth of cancer cells and prevents the patient's immune system from rejecting the donor's stem cells. Healthy stem cells from a donor that are infused into the patient help the patient's bone marrow make blood cells; red blood cells, white blood cells, and platelets. Sometimes, however, the transplanted donor cells can cause an immune response against the body's normal cells, which is called graft-versus-host disease (GVHD). Giving cyclophosphamide after transplant may prevent this from happening or may make chronic GVHD less severe.

Detailed Summary:

PRIMARY OBJECTIVES:

I. The primary objective of this study is to assess outcomes when high-dose cyclophosphamide (CY) is administered on days 3 and 4 followed by cyclosporine (CSP) after human leukocyte antigen (HLA)-matched related or unrelated mobilized blood cell transplantation with total-body irradiation (TBI) or busulfan (BU)-based conditioning.

SECONDARY OBJECTIVES:

I. The secondary objective of this study is to assess hematopoietic cell transplantation (HCT) outcomes when withdrawal of CSP is accelerated in patients without acute graft-versus-host disease (GVHD).

OUTLINE: Patients' conditioning regimens are determined by the Clinical Coordinator after consultation with the attending physician. Based on disease, patients receive either TBI or fludarabine and busulfan.

PREPARATIVE REGIMEN: Patients receive TBI twice daily (BID) on days -4 or -3 to -1. Some patients also receive fludarabine intravenously (IV) daily on days -5 to -2 and busulfan IV over 3 hours once daily (QD) or over 2 hours every 6 hours on days -5 to -2. Patients may also undergo central nervous system (CNS) prophylaxis, testicular irradiation, and/or involved field irradiation as per standard practice.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation (PBSCT) on day 0 per standard practice.

GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 1-2 hours on days 3-4. Patients also receive cyclosporine IV every 12 hours or every 8 hours beginning on day 5 with taper on days 56-126.

Treatment continues in the abse
Sponsor: Fred Hutchinson Cancer Research Center

Current Primary Outcome: Chronic GVHD Requiring Systemic Immunosuppressive Treatment [ Time Frame: At 1 year after transplantation ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Donor Engraftment [ Time Frame: At day 28 ]
  Donor engraftment is defined as the count (percent) of patients with full donor chimerism. Full donor chimerism is defined as at least 95% donor CD3 cells in peripheral blood.
• Grades II-IV and III-IV Acute GVHD [ Time Frame: Through day +100 post-transplant ]
  Grades II-IV and III-IV GVHD will be assessed with the use of cumulative incidence plots.
• Duration of Systemic Immunosuppressive Treatment [ Time Frame: Up to 5 years ]
  The need for additional immunosuppressive treatment with agents other than those used for prophylaxis, the reasons for their administration (acute GVHD, chronic GVHD, or other reasons) and the duration of its administration will be determined. Patients will be monitored to determine the duration of systemic immunosuppressive treatment. Primary and secondary treatment of acute GVHD and withdrawal of systemic immunosuppressive treatment will be assessed with the use of cumulative incidence plots.
• Persistent or Recurrent Malignancy After HCT [ Time Frame: At 2 years ]
  Recurrent or progressive malignancy will be assessed with the use of cumulative incidence plots. Recurrent malignancy will be defined by hematologic criteria. Recurrent malignancy will also be defined as any unplanned medical intervention designed to prevent progression of malignant disease in patients who have molecular, cytogenetic or flow-cytometric evidence of malignant cells after transplantation.
• Non-relapse Mortality [ Time Frame: At 2 years ]
  Defined as death in the absence of recurrent or progressive malignancy after HCT. Non-relapse morality will be assessed with the use of cumulative incidence plots. This secondary endpoint will be characterized and presented as a cumulative incidence.
• Overall Survival [ Time Frame: At 1 year post-transplant ]
  Overall survival will be evaluated as Kaplan-Meier estimates.
• Disease-free Survival [ Time Frame: At 1 year post-transplant ]
  Disease-free survival will be evaluated as Kaplan-Meier estimates.
• Hematologic Recovery [ Time Frame: Up to day +100 ]
  Descriptive statistics will be used to assess the median days of neutrophil and platelet recovery. The day of neutrophil recovery is defined as the first day of three consecutive lab values on different days, after the conditioning regimen-induced nadir of blood counts, that the absolute neutrophil count is > 500/uL. The day of platelet recovery is defined as the first day of three consecutive lab values on different days, after the conditioning regimen-induced nadir of blood counts, that the platelet count is >= 20,000/uL without platelet transfusion support in the seven days prior.
• Graft Failure [ Time Frame: By greater than or equal to 28 days post-transplant ]
  Descriptive statistics will be used to assess the incidence of primary graft failure and secondary graft failure. Primary graft failure is defined as failure to achieve a sustained neutrophil count of >= 500/uL by >= 28 days post-transplant. Secondary graft failure is defined as the decline in neutrophil count to < 500/uL after achieving engraftment which is unrelated to infection or drug effect and is unresponsive to stimulation by growth factors.

Original Secondary Outcome:

• Donor Engraftment [ Time Frame: At day 28 ]
• Grades II-IV and III-IV Acute GVHD [ Time Frame: Through day +100 post-transplant ]
• Duration of Systemic Immunosuppressive Treatment [ Time Frame: Weekly after engraftment to day 100; days 80, 100, and180; and then annually for 5 years ]
• Persistent or Recurrent Malignancy After HCT [ Time Frame: At days 28, 56, and180 and then annually for 5 years ]
• Death without prior persistent or recurrent malignancy (non-relapse mortality) [ Time Frame: At day 100 and at 1 year after transplant ]
• Overall Survival [ Time Frame: At 1 year after transplantation ]
• Disease-free survival (survival without persistent or recurrent malignancy) [ Time Frame: At 1 year after transplantation ]
• Hematologic Recovery [ Time Frame: Daily until engraftment and then weekly until day +100 ]
• Graft Failure [ Time Frame: By greater than or equal to 28 days post-transplant ]

Dates:
Date Received: August 31, 2011
Date Started: September 2011
Date Completion:
Last Updated: May 17, 2017
Last Verified: May 2017