Study of Fludarabine Based Conditioning for Allogeneic Stem Cell Transplantation for Myelofibrosis
Condition: Myelofibrosis
MeSH terms: Primary Myelofibrosis
Study type: Interventional
Phase: Phase 2

Summary: 
      Stem cell transplantation is used to treat may types of diseases. There a 2 types of
      transplants, conventional (very intense) and reduced intensity-non-myeloablative, also called
      mini-transplants.

      This study proposes to use a conditioning regimen for allogeneic transplantation along with a
      reduced intensity transplant. Conditioning regiment is the name for the combination of
      chemotherapy drugs that is given to patients before receiving a transplantation of donor stem
      cells. It is hoped that the regimen designed for this study proves to be less toxic and has
      an equal or better anticancer effect than the regimens that are normally used. The regimen
      being used is a combination of two chemotherapy drugs, fludarabine and melphalan. This
      regimen has been studied in recipients of matched sibling transplants and in recipients of
      alternative donor stem cells in other hematologic malignancies. Those subjects, who receive
      stem cells from an unrelated donor, will also receive and additional drug called ATG or anti
      thymocyte globulin. ATG suppresses the immune system, thus reducing the chances for the
      recipient rejecting the transplant (graft).

      The purpose of this study is to observe if reduced intensity transplants can be used to allow
      engraftment or "take" of the donor's bone marrow. Studies conducted in the past show this
      type of transplant is much less toxic than traditional bone marrow transplants. Reduced
      intensity transplants may be better tolerated by patients who may experience serious side
      effects from standard (very intense) stem cell transplant.

      The study has been recently amended to follow all subjects for survival.
    

Detailed description: 
      This study is designed as a single arm Phase II clinical trial in patients with myelofibrosis
      who are eligible for transplantation from a related donor or from an unrelated donor source.
      Patients will be accrued into two separate strata defined by donor type. Each of the two
      strata will be analyzed separately.

      Patients will be followed yearly from time of enrollment into the study to assess clinical
      response and overall, progression and event free survival, as well as incidence and degree of
      acute and chronic GVHD. We will estimate cumulative survival and transplant related mortality
      in patients enrolled in each of the two strata.
    

Intervention name(s): Fludarabine, Melphalan +/- ATG
Intervention type(s): Drug
Intervention description(s): Conditioning regimen for Allogenic Stem Cell Transplant:
Related Donor Fludarabine days -6 to -2 (30mg/m2 IVPB over 30 minutes daily) Melphalan days -3 to -2 (70mg/m2 IVPB over 30 minutes daily)
Unrelated Donor Fludarabine days -6 to -2 (30mg/m2 IVPB over 30 minutes daily) Melphalan days -3 to -2 (70mg/m2 IVPB over 30 minutes daily) ATG (Thymoglobulin®) days -3 to -1 (0.5 mg/kg IV on day -3 [given over 6 hours], and 2 mg/kg on days -2 and -1 [given over 4 hours])
Intervention MeSH terms: Fludarabine; Melphalan
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Myelofibrosis; Myeloproliferative disease; Stem Cell Transplant; Allogeneic Transplant; Conditioning Regimen; Reduced Intensity Regimen; Fludarabine; Melphalan; ATG