Clinical Trial: Umbilical Cord Blood Transplant, Cyclophosphamide, Fludarabine Phosphate, and Total-Body Irradiation in Treating Patients With Hematologic Disease

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

Official Title: Transplantation of Umbilical Cord Blood for Patients With Hematological Diseases With Cyclophosphamide/Fludarabine/Total Body Irradiation Myeloablative Preparative Regimen

Brief Summary: This phase II trial studies how well giving an umbilical cord blood transplant together with cyclophosphamide, fludarabine phosphate, and total-body irradiation (TBI) works in treating patients with hematologic disease. Giving chemotherapy, such as cyclophosphamide and fludarabine phosphate, and TBI before a donor umbilical cord blood transplant helps stop the growth of cancer and abnormal cells and helps 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. Giving cyclosporine and mycophenolate mofetil after transplant may stop this from happening.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the one year survival of patients undergoing umbilical cord blood transplantation (UCBT) after a myeloablative preparative regimen consisting of cyclophosphamide (CY), fludarabine (FLU), and fractionated total body irradiation (TBI).

SECONDARY OBJECTIVES:

I. Incidence of transplant-related mortality (TRM) at 6 months.

II. Chimerism at multiple time points.

III. Incidence of neutrophil engraftment at day 42.

IV. Incidence of platelet engraftment 6 months.

V. Incidence of acute graft-versus-host disease (GVHD) grade II-IV and grade III-IV at day 100.

VI. Incidence of chronic GVHD at day 100, 1 year and 2 years.

VII. Incidence of clinically significant infections at 6 months, 1 year and 2 years.

VIII. Incidence of disease free survival at 1 and 2 years.

IX. Incidence of relapse at 1 and 2 years.

OUTLINE:

Patients receive myeloablative conditioning comprising fludarabine phosphate intravenously (IV) over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 and -6, and undergo TBI twice daily (BID) on days -4 to -1. Patients then undergo single- or double-unit UCBT on day 0.

Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour every 8 or 12 hours, then cyclosporine orally (PO)
Sponsor: Fred Hutchinson Cancer Research Center

Current Primary Outcome: Overall survival [ Time Frame: 1 year ]

A non-statistical comparison with historical controls will be made. Monitoring will take place separately for the single and double UCBT cohorts.


Original Primary Outcome: Overall survival at 1-year

Current Secondary Outcome:

  • Chimerism analysis [ Time Frame: Assessed up to 2 years ]
    Monitoring will take place separately for the single and double UCBT cohorts. Chimerism studies from peripheral blood and bone marrow samples will be sorted for CD3, CD14, CD33, and CD56 cells.
  • Incidence of chronic GVHD [ Time Frame: Up to 2 years ]
    Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level.
  • Incidence of clinically significant infections [ Time Frame: Up to 2 years ]
    Monitoring will take place separately for the single and double UCBT cohorts.
  • Incidence of grade II-IV and III-IV acute GVHD [ Time Frame: At day 100 ]
    Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level. Monitoring will take place separately for the single and double UCBT cohorts.
  • Incidence of neutrophil engraftment [ Time Frame: At day 42 ]
    Monitoring will take place separately for the single and double UCBT cohorts.
  • Incidence of platelet recovery [ Time Frame: At 6 months ]
    Monitoring will take place separately for the single and double UCBT cohorts.
  • Incidence of relapse [ Time Frame: Up to 2 years ]
    Cumulative incidence estimates will be used to summarize the time-to-event outcomes.
  • Incidence of transplant-related mortality [ Time Frame: At 6 months ]
    Monitoring will take place separately for the single and double UCBT cohorts.
  • Progression-free survival [ Time Frame: Up to 2 years ]
    A non-statistical comparison with historical controls will be made. Cumulative incidence estimates will be used to summarize the time-to-event outcomes. Monitoring will take place separately for the single and double UCBT cohorts.


Original Secondary Outcome:

  • Transplant-related mortality at 6 months
  • Chimerism at multiple time points
  • Neutrophil engraftment at day 42
  • Platelet recovery at 6 months
  • Acute graft-versus-host disease (GVHD)
  • Chronic GVHD
  • Clinically significant infections at multiple time points
  • Relapse at 1 and 2 years
  • Progression-free survival at 1 and 2 years
  • Comparison of single unit UCB transplants with historical controls
  • Comparison of single unit UCB transplants with double unit UCB transplants


Information By: Fred Hutchinson Cancer Research Center

Dates:
Date Received: July 19, 2008
Date Started: November 2005
Date Completion:
Last Updated: January 11, 2017
Last Verified: January 2017