Clinical Trial: Fludarabine Phosphate and Total-Body Radiation Followed by Donor Peripheral Blood Stem Cell Transplant and Immunosuppression in Treating Patients With Hematologic Malignancies

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

Official Title: Nonmyeloablative PBSC Allografting From HLA Matched Related Donors Using Fludarabine and/or Low Dose TBI With Disease-Risk Based Immunosuppression

Brief Summary: This clinical trial studies fludarabine phosphate and total-body radiation followed by donor peripheral blood stem cell transplant and immunosuppression in treating patients with 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. Giving total-body irradiation together with fludarabine phosphate, cyclosporine, and mycophenolate mofetil before transplant may stop this from happening.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To estimate the rate of grade III/IV graft-versus-host disease (GVHD) in patients treated with low-dose total body irradiation (TBI), fludarabine (fludarabine phosphate), PBSC infusion and immunosuppression with mycophenolate mofetil and a disease risk-based cyclosporine taper.

II. To estimate the risk of graft rejection, GVHD, disease response, non-relapse mortality and the incidence and severity of infectious complications using this treatment strategy.

OUTLINE: Patients are assigned to 1 of 2 treatment groups.

ARM I (indolent disease):

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 and undergo TBI on day 0.

TRANSPLANTATION: Patients undergo donor peripheral blood stem cell transplantation (PBSCT) on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) or IV every 8-12 hours on days -3 to 56 with a taper to day 180 and mycophenolate mofetil PO BID or IV every 8-12 hours on days 0 to 27.

ARM II (aggressive disease):

CONDITIONING REGIMEN: Patients receive fludarabine phosphate and undergo TBI as in Arm I.

TRANSPLANTATION: Patients undergo donor PBSCT on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV every 8-12 hours on days -3 to 56 with a taper to day 70 and mycophenolate mofetil as in Arm I.

After complet
Sponsor: Fred Hutchinson Cancer Research Center

Current Primary Outcome:

  • Probability of severe (grade III/IV) GVHD in each arm [ Time Frame: Up to day 84 ]
    95% confidence interval will be calculated.
  • Probability of severe (grade III/IV) GVHD in each arm [ Time Frame: Up to 5 years ]
    95% confidence intervals will be calculated.


Original Primary Outcome:

Current Secondary Outcome:

  • Incidence of graft rejection [ Time Frame: Day 28 ]
    Chimerism analysis by fluorescent in situ hybridization (FISH) or variable number tandem repeat (VNTR). Examined and reported in a descriptive manner. Confidence intervals will be presented.
  • Incidence of graft rejection [ Time Frame: Day 56 ]
    Chimerism analysis by FISH or VNTR. Examined and reported in a descriptive manner. Confidence intervals will be presented.
  • Incidence of graft rejection [ Time Frame: Day 84 ]
    Chimerism analysis by FISH or VNTR. Examined and reported in a descriptive manner. Confidence intervals will be presented.
  • Incidence of graft rejection [ Time Frame: Day 180 ]
    Chimerism analysis by FISH or VNTR. Examined and reported in a descriptive manner. Confidence intervals will be presented.
  • Incidence of graft rejection [ Time Frame: Day 365 ]
    Chimerism analysis by FISH or VNTR. Examined and reported in a descriptive manner. Confidence intervals will be presented.
  • Incidence of non-relapse mortality [ Time Frame: Up to 5 years ]
    Examined and reported in a descriptive manner. Confidence intervals will be presented.
  • Incidence of infectious complications [ Time Frame: Up to 5 years ]
    Examined and reported in a descriptive manner. Confidence intervals will be presented.
  • Severity of infectious complications [ Time Frame: Up to 5 years ]
    Examined and reported in a descriptive manner. Confidence intervals will be presented.


Original Secondary Outcome:

Information By: Fred Hutchinson Cancer Research Center

Dates:
Date Received: April 10, 2001
Date Started: December 2000
Date Completion:
Last Updated: November 28, 2016
Last Verified: November 2016